Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 536
Filtrar
1.
Front Pharmacol ; 12: 785403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899349

RESUMO

Background and purpose: FXR is a promising target for the treatment of human cholestatic liver disease (CLD). SIRT1 is a deacetylase which promotes FXR activity through deacetylating FXR. Pterostilbene (PTE) is an activator of SIRT1. However, the role of PTE in cholestasis has so far not been investigated. We examined whether PTE treatment alleviate liver injury in DDC or ANIT-induced experimental cholestasis, and explored the underlying mechanisms. Experimental approach: Mice with DDC- or ANIT-induced cholestasis were treated with different dose of PTE. Primary hepatocytes and bone marrow derived macrophages were used in vitro to assess the molecular mechanism by which PTE may improve CLD. Identical doses of UDCA or PTE were administered to DDC- or ANIT-induced cholestasis mice. Key results: PTE intervention attenuated DDC or ANIT-induced cholestasis. PTE inhibited macrophage infiltration and activation in mouse liver through the SIRT1-p53 signaling pathway, and it improved hepatic bile metabolism through the SIRT1-FXR signaling pathway. Compare with UDCA, the same doses of PTE was more effective in improving cholestatic liver injury caused by DDC or ANIT. Conclusion and implications: SIRT1 activation in macrophages may be an effective CLD treatment avenue. Using CLD models, we thus identified PTE as a novel clinical candidate compound for the treatment of CLD.

2.
Int J Clin Exp Pathol ; 14(11): 1090-1094, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900077

RESUMO

We report a rare case of double primary germ cell tumor: right ovarian yolk sac tumor and left ovarian dysgerminoma. A 45 year-old woman was admitted to our hospital due to irregular bleeding for 2 days and extended menstrual period. Right ovarian mass was discovered on transvaginal ultrasound. The pathology results revealed that right ovarian yolk sac tumor and left ovarian dysgerminoma. Total abdominal hysterectomy with bilateral salpingo-oophorectomy with debulking with pelvic lymphadenectomy was performed. The patient underwent adjuvant chemotherapy with BEP six courses in four months and AFP dropped from 8490 ng/ml to nearly 10 ng/ml. Conclusion: Total abdominal hysterectomy with bilateral salpingo-oophorectomy followed by combination chemotherapy must be the treatment of first choice of germ cell tumor.

3.
Front Pharmacol ; 12: 779652, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950037

RESUMO

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and has become a serious public health problem worldwide. Dipeptidyl peptidase-4 (DPP4) inhibitors, an emerging drug for the treatment of diabetes, have been found to have renoprotective effects in addition to glucose-lowering effects and therefore have the potential to be a treatment modality for DKD. Lobeliae Chinensis Herba (LCH), a traditional Chinese herb widely used in the treatment of diabetes, has recently been found to have a hypoglycaemic mechanism related to the inhibition of DPP4. Firstly, analysis of single-cell sequencing data from mouse kidneys in the National Center for Biotechnology Information (NCBI) database revealed that DPP4 was specifically upregulated in DKD podocytes and was associated with podocyte proliferation. Subsequently, the network pharmacology approach was applied to the screening of compounds. Twelve LCH active ingredients targeting DPP4 were extracted from the Traditional Chinese Medicine System Pharmacology (TCMSP) database. In addition, these 12 compounds and DPP4 were molecularly docked to predict the probability of them affecting DPP4 activity. In vitro, Quercetin, Methyl rosmarinate, Kaempferol, Diosmetin and Acacetin were demonstrated to retard podocyte proliferation by inhibiting DPP4 activity and were the top five compounds predicted by molecular docking to be the most likely to affect DPP4 activity. The half maximal inhibitory concentration (IC50) of the five compounds for DPP4 activity were as follows. Acacetin Log IC50 = -8.349, 95%CI (-9.266, -7.265), Diosmtrin Log IC50 = -8.419, 95%CI (-8.889, -7.950), Log IC50 = -8.349, 95%CI (-9.266, -7.265), Methyl rosmarinate Log IC50 = -8.415, 95%CI (-8.751, -8.085), Kaempferol Log IC50 = -8.297, 95%CI (-9.001, -7.615), Quercetin Log IC50 = -8.864, 95%CI (-9.107, -8.615). Finally, Quercetin, Methyl rosmarinate, Kaempferol, Diosmetin and Acacetin qualified for pharmacokinetic and drug similarity screening and have the potential to be the most promising oral agents for the treatment of DKD.

4.
Cancer Cell Int ; 21(1): 699, 2021 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-34933678

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA) is one of the deadliest cancers of the digestive tract. The prognosis of CCA is poor and the 5-year survival rate is low. Bioinformatic analysis showed that early mitotic inhibitor 2 (EMI2) was overexpressed in CCA but the underlying mechanism is not known. METHODS: The data on bile duct carcinoma from TCGA and GEO databases were used to detect the expression of EMI2. The transcription factors of EMI2 were predicted using JASPAR and PROMO databases. Among the predicted transcription factors, YY1 has been rarely reported in cholangiocarcinoma, and was verified using the luciferase reporter gene assay. RT-PCR was performed to predict the downstream pathway of EMI2, and PI3K/Akt was suspected to be associated with it. Subsequently, in vivo and in vitro experiments were conducted to verify the effects of silencing and overexpressing EMI2 and YY1 on the proliferation, invasion, and metastasis of the bile duct cancer cells. RESULTS: EMI2 was highly expressed in CCA. Silencing EMI2 inhibited the proliferation, invasion, and migration of CCA cells, arrested cell cycle in the G1 phase, and promoted of apoptosis. The luciferase reporter gene assay showed that YY1 bound to the promoter region of EMI2, and after silencing YY1, the expression of EMI2 decreased and the progression of CCA was inhibited. Moreover, key proteins in the PI3K/Akt signaling pathway decreased after silencing EMI2. CONCLUSION: EMI2 may be one of the direct targets of YY1 and promotes the progression of CCA through the PI3K/Akt signaling pathway.

5.
Diabetologia ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34913989

RESUMO

AIMS/HYPOTHESIS: Type 2 diabetes is associated with a reduction in skeletal muscle mass; however, how the progression of sarcopenia is induced and regulated remains largely unknown. We aimed to find out whether a specific microRNA (miR) may contribute to skeletal muscle atrophy in type 2 diabetes. METHODS: Adeno-associated virus (AAV)-mediated skeletal muscle miR-193b overexpression in C57BLKS/J mice, and skeletal muscle miR-193b deficiency in db/db mice were used to explore the function of miR-193b in muscle loss. In C57BL/6 J mice, tibialis anterior-specific deletion of 3-phosphoinositide-dependent protein kinase-1 (PDK1), mediated by in situ AAV injection, was used to confirm whether miR-193b regulates muscle growth through PDK1. Serum miR-193b levels were also analysed in healthy individuals (n = 20) and those with type 2 diabetes (n = 20), and correlations of miR-193b levels with HbA1c, fasting blood glucose (FBG), body composition, triacylglycerols and C-peptide were assessed. RESULTS: In this study, we found that serum miR-193b levels increased in individuals with type 2 diabetes and negatively correlated with muscle mass in these participants. Functional studies further showed that AAV-mediated overexpression of miR-193b induced muscle loss and dysfunction in healthy mice. In contrast, suppression of miR-193b attenuated muscle loss and dysfunction in db/db mice. Mechanistic analysis revealed that miR-193b could target Pdk1 expression to inactivate the Akt/mammalian target of rapamycin (mTOR)/p70S6 kinase (S6K) pathway, thereby inhibiting protein synthesis. Therefore, knockdown of PDK1 in healthy mice blocked miR-193b-induced inactivation of the Akt/mTOR/S6K pathway and impairment of muscle growth. CONCLUSIONS/INTERPRETATION: Our results identified a previously unrecognised role of miR-193b in muscle function and mass that could be a potential therapeutic target for treating sarcopenia.

6.
Front Cell Dev Biol ; 9: 757643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957095

RESUMO

Fibrinogen-like 1 (FGL1) is involved in liver injury and liver regeneration, but its role in placenta and preeclampsia (PE) remains unclear. We assessed FGL1 expression in serum and placenta from L-NAME-induced PE-like mouse and in women with (n = 38) and without (n = 42) PE. For the mouse study, pregnant C57Bl/6 mouse (n = 6/group) were subcutaneously administered L-NAME with or without FGL1 once daily starting on days 7-14 of pregnancy and were sacrificed on gestational day (GD) 20. Maternal body weight, blood pressure, and urinary protein were assessed during GDs 8-20. The weight and length of the placenta and fetus were assessed. The placental structure was evaluated using hematoxylin staining. In the human study, the sera of the pregnant women during the late trimester were assessed with enzyme-linked immunosorbent assays (ELISAs). FGL1 expression in human trophoblast cell lines under L-NAME stimulation was measured using Western blotting and immunofluorescence staining. The detected FGL1 protein levels in serum and placenta were both significantly upregulated in patients and mouse with PE compared with those in the non-PE groups. FGL1 treatment decreased maternal hypertension and proteinuria, decreased fetal weight in mouse with PE, downregulated proinflammatory cytokine (interleukin-1b and interleukin-6) levels, and maintained the balance between antiangiogenic (fms-like tyrosine kinase-1) and proangiogenic (placental growth factor) substances in the placenta. L-NAME-upregulated FGL1 expression was inhibited following overexpression of FoxO3a. In summary, FoxO3a reduction is a potential pathophysiological mechanism leading to upregulated placental FGL1 expression that may play a pivotal role in preventing PE progression.

7.
Front Med (Lausanne) ; 8: 751586, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957141

RESUMO

Objectives: The World Health Organization proposed intrinsic capacity (IC) model to guide the implementation of person-centered care plan aimed at preserving or reserving functional ability, especially in frail older adults. We aimed to show the trajectory of IC and the overlap between IC impairment and frailty and investigate the correlation between IC domains and frailty status transitions. Method: Longitudinal observational study covering 230 community-dwelling older adults (mean age 84.0 ± 4.5 years) at baseline, and transition information at 2-year follow-up (n = 196). IC was measured by five domains: locomotion, cognition, vitality, psychological, and sensory. Frailty was defined by FRAIL Scale. IC and frailty status transitions were assessed. Logistic regression, odds ratios (OR) and 95% confidence interval (CI) were used for the analysis. Results: The prevalence of frailty was 23.0% and increased up to 41.8% over two years. Regarding frailty transitions, 38.3% of older adults progressed to more frailty status, and 8.6% regressed to lesser frailty status. The prevalence of IC impairment was 67.9% and increased to 81.6% over two years. Regarding IC transitions, 49.2% of adults with no IC impairment at baseline kept stable, and 50.8% developed new IC impairment. Among individuals with IC impairment at baseline, 57.9% worsened, and 13.5% improved. Importantly, IC impairment at baseline existed in 42.4% robust adults, 83.3% pre-frail adults, and 93.3% frail adults. 47.1% individuals who kept non-frail status within two years experienced IC worsened transition. Univariable analysis illustrated that new impaired locomotion, vitality, cognition, and sensory domains increased the risk of non-frail progressed to frail status. After adjusting for covariables, new impaired locomotion (OR = 3.625, 95% CI: 1.348-9.747) and vitality domains (OR = 3.034, 95% CI: 1.229-7.487) were associated with a higher possibility of non-frail progressed to frail status. Conclusion: IC impairment and frailty overlap and co-exist in older adults. IC impairment, especially new impairment in locomotion and vitality are associated with the transitions from non-frail to frail status. It is important that geriatricians tightly monitor IC trajectory and find the new impaired domains to take early action to minimize the public health burden of frailty.

8.
Biomolecules ; 11(11)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34827581

RESUMO

Vertical vibration (VV) is a type of whole body vibration, which induces muscle contraction through vibration to improve muscle strength and bone density. However, the mechanism of VV on muscle cell myotube formation is still unclear. In the current study, we aim to clarify the mechanism involved in VV's stimulation of myotube formation. In order to identify the molecules regulated by VV, we performed proteomics analysis including 2D electrophoresis combined with MALDI-TOF/TOF Mass. Stathmin was identified as a high potential molecule responding to VV stimulation, and we found that under VV stimulation, the expression of stathmin gene and protein increased in a time-dependent manner. In addition, we also confirmed that the increase of stathmin stimulated by VV is mediated through the PI3K/Akt pathway. Furthermore, stathmin siRNA significantly down-regulated the expression of myogenic regulatory factor (MRF) MyoD, decorin, and type I collagen (Col-I), and down-regulated the cellular process regulators such as FGF7, TGFBr1 and PAK3. Taken together, our results confirm that under the stimulation of VV, PI3K/Akt and stathmin would be activated, as well as the up-regulation of MRFs, such as FGF7, TGFBr1 and PAK3 to initiate myogenesis. It also showed that the response of MRF to VV stimulation was significantly related to stathmin expression, which also confirmed the importance of stathmin in the entire myotube formation process. This study may provide evidence of stathmin as a biological indicator of VV to increase muscle strength.

9.
Life (Basel) ; 11(11)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34833069

RESUMO

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is the most common cause of mortality and neurological disability in infancy after perinatal asphyxia. Reliable biomarkers to predict neurological outcomes of neonates after perinatal asphyxia are still not accessible in clinical practice. METHODS: A prospective cohort study enrolled neonates with perinatal asphyxia. Biochemical blood tests and cerebral Doppler ultrasound were measured within 6 h of age and at the 4th day old. Neurological outcomes were assessed at 1 year old. RESULTS: Sixty-four neonates with perinatal asphyxia were enrolled. Fifty-eight (90%) had hypoxic-ischemic encephalopathy (HIE) including 20 (34%) Stage I, 21 (36%) Stage II, and 17 (29%) Stage III. In the asphyxiated infants without therapeutic hypothermia, HIE stage, PH, and base excess levels within 6 h of age were the predictors of adverse outcomes. In the asphyxiated infants receiving therapeutic hypothermia, HIE stage failed to predict outcomes. Instead, blood lactate levels and pulsatility index (PI) of medial cerebral arteries (MCA) either in 6 h of age or at the 4th day old independently predicted adverse outcomes. CONCLUSIONS: Blood lactate, which is a common accessible test at the hospital and MCA PI on cerebral ultrasound could predict adverse outcomes in asphyxiated infants receiving therapeutic hypothermia.

10.
J Healthc Eng ; 2021: 5031667, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804452

RESUMO

Objective: To explore the correlation between the resistance characteristics of Helicobacter pylori (HP) and antibiotic use density (AUD) in a hospital from 2012 to 2018. Methods: HP strains isolated from Chinese PLA General Hospital from 2012 to 2018 were collected to analyze the drug resistance of clarithromycin, levofloxacin, amoxicillin, and metronidazole, and their correlation with the AUD of the outpatient department and inpatient department was analyzed, respectively. Results: From 2012 to 2018, metronidazole-resistant strains accounted for the largest proportion, followed by clarithromycin and levofloxacin, and amoxicillin-resistant strains accounted for the least. In 2012-2018, the resistance rate of clarithromycin, levofloxacin, amoxicillin, and metronidazole has basically increased year by year; from 2012 to 2018, the highest outpatient AUD in a hospital was amoxicillin, followed by clarithromycin and levofloxacin, metronidazole was the lowest, and the inpatient AUD from high to low was levofloxacin, metronidazole, amoxicillin, and clarithromycin. The drug resistance rate of HP in the hospital from 2012 to 2018 was positively correlated with the AUD of clarithromycin (r = 0.884, P=0.017) and levofloxacin (r = 0.934, P=0.002) in the outpatient department. Conclusions: Helicobacter pylori has the strongest resistance to metronidazole and the worst resistance to amoxicillin in the hospital from 2012 to 2018, being related to the intensity of clarithromycin and levofloxacin in the outpatient department. It may provide certain reference significance for the clinical treatment of Helicobacter pylori.

11.
Nano Lett ; 21(22): 9609-9618, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34726401

RESUMO

Transmembrane MUC18 is highly expressed on most metastatic cancers. Herein, we demonstrate that targeting MUC18 with polydopamine nanoparticles (PDA NPs) and a mild photothermal effect can completely cease the migration of melanoma and breast cancer cells without killing the cells. The inhibited cell migration can be attributed to the altered actin cytoskeleton, cell stiffness, and cell morphology, as revealed by nanomechanical and super resolution fluorescence imaging techniques. Further mechanistic studies at the molecular level show that MUC18 targeted PDA NPs and a mild photothermal treatment produce a synergistic effect on the actin cytoskeleton by downregulating the transmembrane MUC18 and interrupting ezrin-radixin-moesin phosphorylation, thereby releasing the actin cytoskeleton from the cell membrane and compromising force transduction through the actin cytoskeleton to the transmembrane MUC18. Overall, the concept of targeting transmembrane metastatic markers and disrupting their downstream effectors (i.e., actin and actin-binding proteins) opens up a new avenue to cancer therapy.

12.
Nano Lett ; 21(22): 9625-9632, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34730364

RESUMO

Designing a spectrometer without the need for wavelength multiplexing optics can effectively reduce the complexity and physical footprint. On the basis of the computational spectroscopic strategy and combining a broadband-responsive dynamic detector, we successfully demonstrate an optics-free single-detector spectrometer that maps the tunable quantum efficiency of a superconducting nanowire into a matrix to build a solvable mathematical equation. Such a spectrometer can realize a broadband spectral responsivity ranging from 660 to 1900 nm. The spectral resolution at the telecom is sub-10 nm, exceeding the energy resolving capacity of existing infrared single-photon detectors. Meanwhile, benefiting from the optics-free setup, precise time-of-flight measurements can be simultaneously achieved. We have demonstrated a spectral LiDAR with eight spectral channels. This spectrometer scheme paves the way for applying superconducting nanowire detectors in multifunctional spectroscopy and represents a conceptual advancement for on-chip spectroscopy and spectral imaging.

13.
Kidney Dis (Basel) ; 7(5): 391-400, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34604345

RESUMO

Background: The relationship between marital status and CKD is rarely studied. We aimed to explore the effect of marital status on the depression and mortality of patients with CKD. Methods: The data sources came from the NHANES database during 2005-2014 and 3,865 participants were included in this study. We used logistic regression models to examine the relationship between marital status and depression of CKD patients. The Cox proportional hazard models were used to evaluate the association between marital status and mortality of CKD patients. Results: In terms of depression in CKD patients, unmarried patients had a worse situation than married patients. Meanwhile, after adjusting the covariables, unmarried patients had increased risk of depression (OR = 1.26, 95% CI: 1.01-1.57) compared with married CKD patients, especially in males (OR = 1.45, 95% CI: 1.02-2.06) and patients with more than college education level (OR = 12.4, 95% CI: 3.75-41.02). There was a significant relationship between marital status and mortality of general CKD patients (HR = 1.36, 95% CI: 1.17-1.58). Moreover, marriage showed a protective effect against death among male patients, patients with school graduate or less and more than college educational level, patients with high income, and patients in different estimated glomerular filtration rate groups. Conclusions: The use of large numbers of participants has revealed the effect of marital status on CKD patients. Unmarried ones had a higher risk of depression than married ones among CKD patients. Meanwhile, the risk of death was higher in unmarried ones than married ones among CKD patients in this study.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34597439

RESUMO

OBJECTIVE: To examine whether serum procalcitonin (PCT) is useful for differentiating acute pyelonephritis (APN) from asymptomatic bacteriuria and acute cystitis during pregnancy. METHODS: A multicenter prospective observational study was conducted to compare serum white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and PCT level among pregnant women with asymptomatic bacteriuria, acute cystitis, and APN and healthy pregnant women (controls). Utility of WBC count, ESR, CRP, and PCT biomarkers for the prediction of APN during pregnancy were measured. RESULTS: Area under the curve (AUC) values of PCT, CRP, ESR, and WBC count for predicting asymptomatic bacteriuria were 0.576, 0.628, 0.542, and 0.532, respectively; those for predicting acute cystitis were 0.766, 0.735, 0.681, and 0.597, respectively; and those for predicting acute pyelonephritis 0.859, 0.763, 0.711, and 0.732, respectively. Compared with the other inflammatory markers used to predict APN, PCT exhibited the highest AUC (0.859 [95% confidence interval (CI) 0.711-0.935]). A cutoff value of >0.25 ng/ml had a sensitivity of 87% and a specificity of 79%. CONCLUSION: Serum PCT can be a valuable addition to existing methods of differentiating asymptomatic bacteriuria, acute cystitis, and APN during pregnancy and can facilitate the early identification of APN during pregnancy.

15.
Acta Pharmacol Sin ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34667293

RESUMO

Decaprenylphosphoryl-ß-D-ribose oxidase (DprE1) plays important roles in the biosynthesis of mycobacterium cell wall. DprE1 inhibitors have shown great potentials in the development of new regimens for tuberculosis (TB) treatment. In this study, an integrated molecular modeling strategy, which combined computational bioactivity fingerprints and structure-based virtual screening, was employed to identify potential DprE1 inhibitors. Two lead compounds (B2 and H3) that could inhibit DprE1 and thus kill Mycobacterium smegmatis in vitro were identified. Moreover, compound H3 showed potent inhibitory activity against Mycobacterium tuberculosis in vitro (MICMtb = 1.25 µM) and low cytotoxicity against mouse embryo fibroblast NIH-3T3 cells. Our research provided an effective strategy to discover novel anti-TB lead compounds.

16.
Foods ; 10(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34681379

RESUMO

Lotus leaves are often discarded as byproducts in the lotus industry. Polysaccharides are regarded as one of the essentially bioactive components in lotus leaves. Therefore, in order to promote the application of lotus leaves in the functional food industry, the deep eutectic solvent (DES) assisted extraction of polysaccharides from lotus leaves (LLPs) was optimized, and structural and biological properties of LLPs extracted by DES and hot water were further investigated. At the optimal extraction conditions (water content of 61.0% in DES, extraction temperature of 92 °C, liquid-solid ratio of 31.0 mL/g and extraction time of 126 min), the maximum extraction yield (5.38%) was obtained. Furthermore, LLP-D extracted by DES and LLP-W extracted by hot water possessed the same sugar residues, such as 1,4-α-D-GalAp, 1,4-α-D-GalAMep, 1,3,6-ß-D-Galp, 1,4-ß-D-Galp, 1,5-α-L-Araf, and 1,2-α-L-Rhap, suggesting the presence of homogalacturonan (HG), rhamnogalacturonan I and arabinogalactan in both LLP-W and LLP-D. Notably, LLP-D was much richer in HG fraction than that of LLP-W, suggesting that the DES could assist to specifically extract HG from lotus leaves. Additionally, the lower molecular weight and higher content of uronic acids were observed in LLP-D, which might contribute to its much stronger in vitro antioxidant, hypoglycemic, and immunomodulatory effects. These findings suggest that the optimized DES assisted extraction method can be a potential approach for specific extraction of acidic polysaccharides with good bioactivities from lotus leaves for applications in the functional food industry.

17.
Br J Pharmacol ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34713437

RESUMO

BACKGROUND AND PURPOSE: Atherosclerosis is one of the underlying causes of cardiovascular disease. Formation of foam cells and necrotic core in the plaque is a hallmark of atherosclerosis, which results from lipid deposition, apoptosis, and inflammation in macrophages. Macrophage autophagy is a critical anti-atherogenic process and defective autophagy aggravates atherosclerosis by enhancing foam cell formation, apoptosis, and inflammation. Hence, enhancing autophagy can be a strategy for atherosclerosis treatment. Calycosin, a flavonoid from Radix Astragali, displays anti-oxidant and anti-inflammatory activities and therefore is potential to reduce the risk of cardiovascular disease. However, the anti-atherogenic effect of calycosin and the involved mechanism remains unclear. In this study, we assessed the potential benefits of calycosin on autophagy and atherosclerosis, and revealed the underlying mechanism. EXPERIMENTAL APPROACH: In this study, apoE-/- mice were fed high-fat diet for 16 weeks in the presence of calycosin and/or autophagy inhibitor chloroquine, which was followed by determination of atherosclerosis development, autophagy activity, and involved mechanisms. KEY RESULTS: Calycosin protected against atherosclerosis and enhanced plaque stability via promoting autophagy. Calycosin inhibited foam cell formation, inflammation, and apoptosis by enhancing autophagy. MLKL was demonstrated as a new autophagy regulator, which can be negatively regulated by KLF2. Mechanistically, inhibitory effects of calycosin on atherogenesis were via improved autophagy through KLF2-MLKL signalling pathway modulation. CONCLUSIONS AND IMPLICATIONS: This study demonstrated the atheroprotective effect of calycosin was through upregulating KLF2-MLKL-mediated autophagy, which not only proposed novel mechanistic insights into t atherogenesis but also identified calycosin as a potential drug candidate for atherosclerosis treatment.

18.
Medicine (Baltimore) ; 100(43): e27617, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713845

RESUMO

RATIONALE: Mediastinal non-seminomatous germ cell tumors (MNSGCTs) are rare malignancies. Chemotherapy followed by surgical resection has been regarded as the standard management, but treatment options for chemotherapy-refractory patients or those with unresectable tumors are limited, resulting in a very poor prognosis. PATIENT CONCERNS: An 18-year-old female presented with symptoms of cough, chest tightness, and shortness of breath for 2 months, and the symptoms gradually worsened. DIAGNOSIS: Computed tomography (CT) revealed a large mediastinal mass invading the pericardium and great blood vessels. Serum human chorionic gonadotropin (HCG) and α-fetoprotein (AFP) levels were normal. Histopathological examination of biopsy specimens revealed mixed MNSGCT with embryonal carcinoma and immature teratoma components. INTERVENTIONS: The patient achieved complete remission (CR) and long-term survival after multimodal therapy comprising chemotherapy, positron emission tomography/CT (PET/CT)-guided volumetric-modulated arc therapy (VMAT), and anti-angiogenic targeted therapy. OUTCOMES: The patient was followed up for more than 4 years without recurrence, metastasis, or treatment-related adverse effects. LESSONS: The case presented here highlights the importance of multidisciplinary diagnosis and treatment, providing evidence that radiotherapy and anti-angiogenic therapy may play an important role in unresectable or residual tumors after failure of conventional treatments of MNSGCT. Percutaneous biopsy is necessary for diagnosis if the tumor is unresectable, and serum AFP and HCG levels are normal. Additionally, PET/CT is an effective method for evaluation of efficacy and radiotherapy guidance for patients with MNSGCTs.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Mediastino/terapia , Neoplasias Embrionárias de Células Germinativas/terapia , Radioterapia de Intensidade Modulada/métodos , Neoplasias Testiculares/terapia , Adolescente , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Terapia Combinada , Etoposídeo/uso terapêutico , Feminino , Humanos , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Piridinas/uso terapêutico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia
19.
Proc Natl Acad Sci U S A ; 118(43)2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34675076

RESUMO

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

20.
Infect Drug Resist ; 14: 4119-4128, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675557

RESUMO

Objective: To investigate the mutations within the whole rpoB gene of Mycobacterium tuberculosis and analyze their effects on rifampin (RIF) resistance based on crystal structure. Methods: We sequenced the entire rpoB gene in 175 tuberculosis isolates and quantified their minimum inhibitory concentrations using microplate-based assays. Additionally, the structural interactions between wild-type/mutant RpoB and RIF were also analyzed. Results: Results revealed that a total of 34 mutations distributed across 17 different sites within the whole rpoB gene were identified. Of the 34 mutations, 25 could alter the structural interaction between RpoB and RIF and contribute to RIF resistance. Statistical analysis showed that S450L, H445D, H445Y and H445R mutations were associated with high-level RIF resistance, while D435V was associated with moderate-level RIF resistance. Conclusion: Some mutations within the rpoB gene could affect the interaction between RpoB and RIF and thus are associated with RIF resistance. These findings could be helpful to design new antibiotics and develop novel diagnostic tools for drug resistance in TB.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...