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1.
Adv Sci (Weinh) ; 11(21): e2400642, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38647258

ABSTRACT

Kidney stones are a pervasive disease with notoriously high recurrence rates that require more effective treatment strategies. Herein, tartronic acid is introduced as an efficient inhibitor of calcium oxalate monohydrate (COM) crystallization, which is the most prevalent constituent of human kidney stones. A combination of in situ experimental techniques and simulations are employed to compare the inhibitory effects of tartronic acid with those of its molecular analogs. Tartronic acid exhibits an affinity for binding to rapidly growing apical surfaces of COM crystals, thus setting it apart from other inhibitors such as citric acid, the current preventative treatment for kidney stones. Bulk crystallization and in situ atomic force microscopy (AFM) measurements confirm the mechanism by which tartronic acid interacts with COM crystal surfaces and inhibits growth. These findings are consistent with in vivo studies that reveal the efficacy of tartronic acid is similar to that of citric acid in mouse models of hyperoxaluria regarding their inhibitory effect on stone formation and alleviating stone-related physical harm. In summary, these findings highlight the potential of tartronic acid as a promising alternative to citric acid for the management of calcium oxalate nephropathies, offering a new option for clinical intervention in cases of kidney stones.


Subject(s)
Calcium Oxalate , Crystallization , Disease Models, Animal , Kidney Calculi , Calcium Oxalate/chemistry , Calcium Oxalate/metabolism , Mice , Animals , Kidney Calculi/drug therapy , Kidney Calculi/metabolism , Microscopy, Atomic Force , Humans , Mice, Inbred C57BL
2.
Dalton Trans ; 52(27): 9275-9281, 2023 Jul 11.
Article in English | MEDLINE | ID: mdl-37341552

ABSTRACT

In this paper, a cyclic (CuIpz)3·CH3CN (1) precursor and a mixed-valence pentanuclear complex CuI3CuII2(OH)pz6·CH3CN (2) have been synthesized and structurally characterized by single-crystal X-ray diffraction, where pzH = 4-chloro-3,5-diphenylpyrazole. The excellent catalytic activity of 2 has been demonstrated in the chemical fixation of CO2 into value-added cyclic carbonates, which can be carried out at ambient pressure and room temperature along with ultra-high yield and perfect steric hindrance tolerance. Based on density functional theory (DFT) calculations and comparison with the catalytic performance of 1, it is proposed that the coordinatively unsaturated CuII atoms of 2 are probably the active sites for this catalytic reaction.

3.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(2): 172-178, 2023 Feb 15.
Article in Chinese | MEDLINE | ID: mdl-36854694

ABSTRACT

OBJECTIVES: To investigate the change in the distribution of memory B cell subsets in children with frequently relapsing nephrotic syndrome (FRNS) during the course of the disease. METHODS: A total of 35 children with primary nephrotic syndrome (PNS) who attended the Department of Pediatrics of the Affiliated Hospital of Xuzhou Medical University from October 2020 to October 2021 were enrolled as subjects in this prospective study. According to the response to glucocorticoid (GC) therapy and frequency of recurrence, the children were divided into two groups: FRNS (n=20) and non-FRNS (NFRNS; n=15). Fifteen children who underwent physical examination were enrolled as the control group. The change in memory B cells after GC therapy was compared between groups, and its correlation with clinical indicators was analyzed. RESULTS: Before treatment, the FRNS and NFRNS groups had significantly increased percentages of total B cells, total memory B cells, IgD+ memory B cells, and IgE+ memory B cells compared with the control group, and the FRNS group had significantly greater increases than the NFRNS group (P<0.05); the FRNS group had a significantly lower percentage of class-switched memory B cells than the NFRNS and control groups (P<0.05). After treatment, the FRNS and NFRNS groups had significant reductions in the percentages of total B cells, total memory B cells, IgM+IgD+ memory B cells, IgM+ memory B cells, IgE+ memory B cells, IgD+ memory B cells, and IgG+ memory B cells (P<0.05) and a significant increase in the percentage of class-switched memory B cells (P<0.05). The FRNS group had a significantly higher urinary protein quantification than the NFRNS and control groups (P<0.05) and a significantly lower level of albumin than the control group (P<0.05). In the FRNS group, urinary protein quantification was negatively correlated with the percentage of class-switched memory B cells and was positively correlated with the percentage of IgE+ memory B cells (P<0.05). CONCLUSIONS: Abnormal distribution of memory B cell subsets may be observed in children with FRNS, and the percentages of IgE+ memory B cells and class-switched memory B cells can be used as positive and negative correlation factors for predicting recurrence after GC therapy in these children.


Subject(s)
B-Lymphocyte Subsets , Nephrotic Syndrome , Child , Humans , B-Lymphocyte Subsets/metabolism , Immunoglobulin E , Immunoglobulin M , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/immunology , Prospective Studies , Glucocorticoids/therapeutic use
4.
BMC Med Educ ; 22(1): 512, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35773709

ABSTRACT

OBJECTIVE: To study the effect of the problem-based learning (PBL) method in ultrasonography (US) resident standardization training during the COVID-19 pandemic. METHODS: Fifty residents were divided into two groups to participate in a 30-day US training program. The residents in the observation group underwent PBL combined with the lecture-based learning (LBL) method, while the residents in the control group experienced the LBL method alone, with 25 residents in each group. A basic theoretical test, practical examination, and questionnaire were used to evaluate the teaching effect of the PBL + LBL method and the LBL method alone. RESULTS: The basic theoretical pretest score of the observation group was not significantly different from that of the control group. However, the posttest theoretical score and practical score were significantly higher in the observation group than in the control group (P < 0.01). The results of the questionnaire showed that the resident satisfaction level in the observation group with PBL combined with the LBL method was 96%, which was significantly higher than that of the control group with the LBL method alone (80%) (P < 0.05). CONCLUSION: The combination of PBL with the LBL method has obvious advantages over the LBL method alone in regard to the training of US residents during the COVID-19 pandemic.


Subject(s)
COVID-19 , Problem-Based Learning , Humans , Pandemics , Problem-Based Learning/methods , Reference Standards , Teaching , Ultrasonography
5.
Influenza Other Respir Viruses ; 16(3): 395-401, 2022 05.
Article in English | MEDLINE | ID: mdl-34796652

ABSTRACT

BACKGROUND: The pandemic of COVID-19 has a persistent impact on global health, yet its sequelae need to be addressed at a wide scale around the globe. This study aims to investigate the characteristics, prevalence, and risk factors for mid-term (>6 months) clinical sequelae in a cohort of COVID-19 survivors. METHODS: Totally 715 COVID-19 survivors discharged before April 1, 2020, from three medical centers in Wuhan, China, were included. The longitudinal study was conducted by telephone interviews based on a questionnaire including the clinical sequelae of general, respiratory, and cardiovascular systems. Demographics and some characteristics of clinical sequelae of the survivors were recorded and analyzed. Multivariate logistic regression analysis was applied to explore the risk factors for the sequelae. RESULTS: The median time interval from discharge to telephone interview was 225.0 days. The COVID-19 survivors' median ages were 69 years, and 51.3% were male. Among them, 29.9% had at least one clinical sequela. There were 19.2%, 22.7%, and 5.0% of the survivors reporting fatigue, respiratory symptoms, and cardiovascular symptoms, respectively. Comorbidities, disease severity, the application of mechanical ventilation and high-flow oxygen therapy, and the history of re-admission were associated with the presence of clinical sequelae. CONCLUSIONS: Our study provides further evidence for the prevalence and characteristics of clinical sequelae of COVID-19 survivors, suggesting long-term monitoring and management is needed for their full recovery.


Subject(s)
COVID-19 , Aged , COVID-19/complications , COVID-19/epidemiology , China/epidemiology , Humans , Longitudinal Studies , Male , Pandemics , SARS-CoV-2 , Survivors
6.
Mol Neurodegener ; 16(1): 48, 2021 07 19.
Article in English | MEDLINE | ID: mdl-34281568

ABSTRACT

BACKGROUND: Understanding the long-term effects of coronavirus disease 2019 (COVID-19) on cognitive function is essential for monitoring the cognitive decline in the elderly population. This study aims to assess the current cognitive status and the longitudinal cognitive decline in elderly patients recovered from COVID-19. METHODS: This cross-sectional study recruited 1539 COVID-19 inpatients aged over 60 years who were discharged from three COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. In total, 466 uninfected spouses of COVID-19 patients were selected as controls. The current cognitive status was assessed using a Chinese version of the Telephone Interview of Cognitive Status-40 (TICS-40) and the longitudinal cognitive decline was assessed using an Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Cognitive assessments were performed 6 months after patient discharge. RESULTS: Compared with controls, COVID-19 patients had lower TICS-40 scores and higher IQCODE scores [TICS-40 median (IQR): 29 (25 to 32) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.19 (3.00 to 3.63) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had lower TICS-40 scores and higher IQCODE scores than non-severe COVID-19 patients [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR): 3.63 (3.13 to 4.31) vs. 3.13 (3.00 to 3.56), p < 0.001] and controls [TICS-40 median (IQR): 24 (18 to 28) vs. 30 (26 to 33), p < 0.001; IQCODE median (IQR) 3.63 (3.13 to 4.31) vs. 3.06 (3.00 to 3.38), p < 0.001]. Severe COVID-19 patients had a higher proportion of cases with current cognitive impairment and longitudinal cognitive decline than non-severe COVID-19 patients [dementia: 25 (10.50 %) vs. 9 (0.69 %), p < 0.001; Mild cognitive impairment (MCI): 60 (25.21 %) vs. 63 (4.84 %), p < 0.001] and controls [dementia: 25 (10.50 %) vs. 0 (0 %), p < 0.001; MCI: 60 (25.21 %) vs. 20 (4.29 %), p < 0.001)]. COVID-19 severity, delirium and COPD were risk factors of current cognitive impairment. Low education level, severe COVID-19, delirium, hypertension and COPD were risk factors of longitudinal cognitive decline. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with an increased risk of long-term cognitive decline in elderly population. COVID-19 patients, especially severe patients, should be intensively monitored for post-infection cognitive decline.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/virology , Aged , Aged, 80 and over , COVID-19/epidemiology , China , Cognitive Dysfunction/epidemiology , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Post-Acute COVID-19 Syndrome
7.
Ultrasound Med Biol ; 47(7): 1737-1746, 2021 07.
Article in English | MEDLINE | ID: mdl-33838937

ABSTRACT

A portion of detected breast masses might be overrated by using the Breast Imaging-Reporting and Data System ultrasonography (BI-RADS US) lexicon. A principal component regression-based contrast-enhanced ultrasound (PCR-CEUS) evaluation system was built to quantitatively illustrate whether CEUS could help radiologists to differentiate 4A masses. The PCR-CEUS evaluation system, based on principal component analysis (PCA) and logistic regression, was verified by random assignment into training and test sets and shown to reduce the data dimension and avoid collinearity in CEUS variables. This prospective study consecutively collected 238 patients with 238 4A masses confirmed pathologically. All enrolled patients accepted CEUS examination. The diagnostic performance of senior and junior radiologists, PCR-CEUS and combined methods was compared. The PCR-CEUS system had consistent diagnostic performance in both the training and test sets, with an area under the curve (AUC) of 0.831 (0.765-0.897), 0.798 (0.7034-0.892) and 0.854 (0.765-0.943) (all P > 0.05). The AUC of the combined diagnostic model (PCR-CEUS + Senior radiologists) was higher than that of senior radiologists, and the combined model had higher sensitivity (0.875 (0.781-0.969) vs. 0.729 (0.603-0.855)) without compromising specificity. Furthermore, the AUC and specificity of the combined model (PCR-CEUS + Junior radiologists) (0.852 (0.787-0.916)) was higher than that of junior radiologists (0.665 (0.592-0.737) (P < 0.00001)). PCR-CEUS demonstrated good ability in differentiating malignant BI-RADS-US 4A masses and was helpful for both senior and junior radiologists.


Subject(s)
Breast Neoplasms/diagnostic imaging , Contrast Media , Ultrasonography, Mammary/methods , Adult , Data Systems , Female , Humans , Middle Aged , Prospective Studies , Radiology , Research Design
8.
J Microbiol Immunol Infect ; 54(6): 1179-1183, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33563561

ABSTRACT

BACKGROUND: The rapid spread of C. difficile 027 has become one of the leading threats of healthcare-associated infections wordwild. However, C. difficile 027 infections have rarely been reported in China. The objective of this study was to strengthen the understanding of the molecular characterizations of C. difficile 027 in China. METHODS: In this study, stool specimens from 176 suspected CDI cases were collected from 1 Jan 2018 to 30 Jun 2019. These specimens were measured by GeneXpert test and C.difficile colonies were identified and analyzed. RESULTS: There were five samples positive for tcdA, tcdB, binary toxin genes and had deletions in tcdC gene. These five Clostridioides difficile isolates belonged to ST1 and confirmed as Clostridioides difficile 027 strains by PCR ribotyping. Through using whole genome sequencing, , we found that these five strains were closely clustered into the same predominant evolutionary branch and were highly similar to C. difficile 027 strain R20291. Antimicrobial susceptibility testing result showed they were highly resistant to fluoroquinolones. CONCLUSIONS: In Our study, five C. difficile 027 isolates were identified and characterized using MLST, PCR ribotyping and whole genome sequencing. We proposed that C. difficile 027 infections are probably neglected in China. Further epidemiological studies across the country together with the introduction of routine diagnostic testing and multi-center or national level surveillance are needed to ascertain the size of this potentially significant problem.


Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/microbiology , Anti-Bacterial Agents/pharmacology , China/epidemiology , Clostridioides difficile/classification , Clostridioides difficile/drug effects , Clostridioides difficile/isolation & purification , Clostridium Infections/epidemiology , Drug Resistance, Bacterial , Genome, Bacterial/genetics , Genotype , Hospitals , Humans , Microbial Sensitivity Tests , Multilocus Sequence Typing , Phylogeny , Retrospective Studies , Ribotyping
10.
Medchemcomm ; 10(8): 1370-1378, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31673307

ABSTRACT

Due to the obvious adverse effects of 5-fluorouracil that limit its clinical usefulness and considering the diverse biological activities of pentacyclic triterpenes, twelve pentacyclic triterpene-5-fluorouracil conjugates were synthesized and their antitumor activities were evaluated. The results indicated that all the single substitution targeted hybrids (7a-12a) possessed much better antiproliferative activities than the double substitution targeted hybrids (7b-12b). Hybrid 12a exhibited good antiproliferative activities against all the tested MDR cell lines. Furthermore, it was revealed that 12a could induce intracellular calcium influx, the generation of ROS, arrest the cell proliferation at the G1 phase, and activate the apoptotic signaling caspase-8, which eventually activates the apoptotic effector caspase-3 and causes the later nuclear apoptosis.

11.
J Zhejiang Univ Sci B ; 19(9): 699-707, 2018.
Article in English | MEDLINE | ID: mdl-30178636

ABSTRACT

Gene therapies have been applied to the treatment of cardiovascular disease, but their use is limited by the need to deliver them to the right target. We have employed targeted contrast ultrasound-mediated gene transfection (TCUMGT) via ultrasound-targeted microbubble destruction (UTMD) to transfer therapeutic genes to specific anatomic and pathological targets. Phospholipid microbubbles (MBs) with pcDNA3.1-human vascular endothelial growth factor 165 (pcDNA3.1-hVEGF165) plasmids targeted to P-selectin (MB+P+VEGFp) were created by conjugating monoclonal antibodies against P-selectin to the lipid shell. These microbubbles were divided into four groups: microbubble only (MB), microbubble+P-selectin (MB+P), microbubble+pcDNA3.1-hVEGF165 plasmid (MB+VEGFp), and microbubble+ P-selectin+pcDNA3.1-hVEGF165 plasmid (MB+P+VEGFp). The reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) results showed that the VEGF gene was successfully transfected by TCUMGT and the efficiency is increased with P-selectin targeting moiety. UTMD-mediated delivery of VEGF increased myocardial vascular density and improved cardiac function, and MB+P+VEGFp delivery showed greater improvement than MB+VEGFp. This study drew support from TCUGMT technology and took advantage of targeted ultrasound contrast agent to identify ischemic myocardium, release pcDNA3.1-hVEGF165 recombinant plasmid, and improve the myocardial microenvironment, so promoting the restoration of myocardial function.


Subject(s)
Genetic Therapy/methods , Microbubbles , Myocardial Ischemia/therapy , P-Selectin/genetics , Transfection/methods , Vascular Endothelial Growth Factor A/genetics , Animals , Male , Myocardial Ischemia/metabolism , Rats , Rats, Sprague-Dawley , Ultrasonics
12.
Ultrasound Med Biol ; 44(6): 1164-1169, 2018 06.
Article in English | MEDLINE | ID: mdl-29551221

ABSTRACT

We investigated the role of the virtual touch tissue quantification (VTQ) technique in diagnosing Hashimoto's thyroiditis (HT) and in distinguishing various HT-related thyroid dysfunctions. Two hundred HT patients and 100 healthy volunteers (the control group) were enrolled. The diagnostic performance of VTQ in predicting HT was calculated as the area under the receiver operating characteristic curve (AZ). The HT patients were further classified into three subgroups on the basis of serologic tests of thyroid function: hyperthyroidism, euthyroidism and hypothyroidism. Comparisons of shear wave velocity (SWV) between three subgroups were evaluated by analysis of variance. The mean SWV of the control group was significantly lower than that of the HT group (1.93 ± 0.33 m/s vs. 2.32 ± 0.49 m/s, p <0.001). Az was 0.734 with a cut-off value of 1.86 m/s for performance of SWV in distinguishing between HT and a healthy thyroid; the sensitivity and specificity were 82.5% and 50.0%, respectively. Mean SWV values in the three HT subgroups (hyperthyroidism [2.07 ± 0.37 cm/s] vs. euthyroidism [2.20 ± 0.40 cm/s] vs. hypothyroidism [2.49 ± 0.46 cm/s]) were significantly different (p <0.05). Our results suggest that VTQ is a promising technique for assessing HT and HT-related thyroid dysfunction.


Subject(s)
Elasticity Imaging Techniques/methods , Hashimoto Disease/diagnostic imaging , Image Processing, Computer-Assisted/methods , Adult , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Thyroid Gland/diagnostic imaging
13.
J Cell Physiol ; 233(8): 6001-6017, 2018 08.
Article in English | MEDLINE | ID: mdl-29271476

ABSTRACT

Single nucleotide polymorphisms (SNPs) in miRNAs are associated with the risk to development of certain human diseases and affect the regulatory capacity of miRNAs. However, the relationship between miRNAs polymorphisms and recurrent pregnancy loss (RPL) is still largely unknown. Our study found that one SNP rs56103835 T>C in miR-323b coding region was associated with the increase risk of human unexplained RPL (URPL), but no differences were found in another SNP rs75330474 C>T. However, in two-locus haplotype analysis, T-C haplotype was associated with an increased risk of URPL. The level of mature miR-323b was obviously up-regulated in cells transfected with T-C haplotype. T-C haplotype inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that paired-box 8 (Pax8) was a functionally relevant target of miR-323b, and its expression was reversely regulated by miR-323b. Besides, the expressions of Pax8 in villous chorionic tissues from URPL patients were lower than controls, contrary to the high expression of miR-323. More importantly, dual-luciferase assay indicated T-C haplotype, increasing miR-323b expression, could down-regulated Pax8 expression. Collectively, our data suggest that T-C haplotype in pre-miR-323b may aggravate the risk of developing URPL and influence the level of mature miR-323b and its target gene Pax8.


Subject(s)
Abortion, Spontaneous/genetics , Asian People/genetics , Genetic Predisposition to Disease/genetics , Haplotypes/genetics , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Case-Control Studies , Cell Line , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation/genetics , Female , HEK293 Cells , HeLa Cells , Humans , Pregnancy
14.
Medicine (Baltimore) ; 96(51): e9465, 2017 Dec.
Article in English | MEDLINE | ID: mdl-29390584

ABSTRACT

RATIONALE: An accessory thyroid gland (ATG) in the right ventricle is an extremely rare condition. Described herein are histological findings of ATG in the right ventricle found in a patient with a normal cervical thyroid gland. PATIENT CONCERNS: A 53-year-old woman was referred to our hospital after experiencing intermittent precordial pain for 2 years. DIAGNOSES: The mass in the right ventricle was diagnosed pathologically as ATG. INTERVENTIONS: Complete excision was performed because of the patient's intermittent precordial pain and to exclude the possibility of malignancy. OUTCOME: The patient's pain was resolved. No recurrence was observed during the 6-month follow-up. LESSONS: After review and analysis of the case, we found that plain and contrast-enhanced computed tomography scans showed that the mass had a similar intensity and enhancement to a cervical thyroid gland, which we think may be a useful clue for making a preoperative diagnosis of ATG.


Subject(s)
Heart Neoplasms/diagnosis , Heart , Thyroid Dysgenesis/diagnosis , Diagnosis, Differential , Female , Humans , Middle Aged , Thyroid Dysgenesis/diagnostic imaging , Tomography, X-Ray Computed
15.
Technol Cancer Res Treat ; 16(4): 512-518, 2017 08.
Article in English | MEDLINE | ID: mdl-27121073

ABSTRACT

Gelsolin is an actin-binding protein and acts as an important regulator of cell survival. This study aimed to determine the function of gelsolin in the radioresistance of non-small cell lung cancer cells. We examined the expression of gelsolin in radioresistant A549 and H460 cells and their parental cells. The effects of gelsolin overexpression and knockdown on the clonogenic survival and apoptosis of non-small cell lung cancer cells after irradiation were studied. The involvement of phosphoinositide 3-kinase/Akt signaling in the action of gelsolin was checked. We found that gelsolin was significantly upregulated in radioresistant A549 and H460 cells. Overexpression of gelsolin significantly ( P < .05) increased the number of colonies from irradiated A549 and H460 cells compared to transfection of empty vector. In contrast, knockdown of gelsolin significantly ( P < .05) suppressed colony formation after irradiation. Gelsolin-overexpressing cells displayed reduced apoptosis in response to irradiation, which was coupled with decreased levels of cleaved caspase-3 and poly adenosine diphosphate-ribose polymerase. Ectopic expression of gelsolin significantly ( P < .05) enhanced the phosphorylation of Akt compared to nontransfected cells. Pretreatment with the phosphoinositide 3-kinase inhibitor LY294002 (20 µmol/L) significantly decreased clonogenic survival and enhanced apoptosis in gelsolin-overexpressing A549 and H460 cells after irradiation. Taken together, gelsolin upregulation promotes radioresistance in non-small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.


Subject(s)
Carcinoma, Non-Small-Cell Lung/radiotherapy , Gelsolin/physiology , Lung Neoplasms/radiotherapy , Radiation Tolerance , Signal Transduction , A549 Cells , Apoptosis , Carcinoma, Non-Small-Cell Lung/metabolism , Gene Expression , Humans , Lung Neoplasms/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Up-Regulation
16.
Biomed Pharmacother ; 80: 338-342, 2016 May.
Article in English | MEDLINE | ID: mdl-27133074

ABSTRACT

Glomerular mesangial cells (MCs) proliferation and extracellular matrix (ECM) accumulation have been recognized as major pathogenic events in the progression of diabetic nephropathy. Betulinic acid (BA), (3ß-hydroxy-lup-20(29)-en-28-oic acid), is a naturally occurring pentacyclic lupane group triterpenoid, and it has been shown to possess glucose-lowering property. However, the role of BA on MC proliferation and ECM accumulation in diabetic condition remains unclear. So, in the present study, we investigated the role of BA on cell proliferation and ECM accumulation in rat glomerular MCs cultured under high glucose (HG) condition. In the current study, we demonstrated that BA suppressed HG-induced MC proliferation, arrested HG-induced cell-cycle progression, reversed HG-inhibited expression of p21(Waf1/Cip1) and p27(Kip1). It also suppressed HG-induced fibronectin (FN) expression in MCs. Furthermore, BA inhibited HG-induced phosphorylation of ERK1/2 and p38MAPK in MCs. In conclusion, our present study demonstrated that BA inhibited HG-induced cell proliferation and FN expression in MCs via inhibiting ERK1/2 and p38MAPK pathways. Thus, BA may serve as a potential drug for the treatment of diabetic nephropathy.


Subject(s)
Fibronectins/metabolism , Glucose/pharmacology , Mesangial Cells/cytology , Mesangial Cells/metabolism , Triterpenes/pharmacology , Animals , Cell Cycle Checkpoints/drug effects , Cell Cycle Proteins/metabolism , Cell Proliferation/drug effects , Cells, Cultured , Extracellular Signal-Regulated MAP Kinases/metabolism , Mesangial Cells/drug effects , Mesangial Cells/enzymology , Mice , Pentacyclic Triterpenes , Phosphorylation/drug effects , Rats , p38 Mitogen-Activated Protein Kinases/metabolism , Betulinic Acid
17.
Oncotarget ; 7(7): 8208-22, 2016 Feb 16.
Article in English | MEDLINE | ID: mdl-26824181

ABSTRACT

MicroRNA-10a (miR-10a) has a wide range of functions in nearly all mammalian tissues and is involved in the occurrence of many diseases. However, it remains unknown whether miR-10a is associated with human recurrent spontaneous abortion (RSA). In this study, we found that rs3809783 A > T in miR-10a coding region was significantly associated with the increase of the risk of human unexplained RSA (URSA) acquisition in a Han-Chinese population. The T allele of rs3809783 hindered the production of mature miR-10a. A to T substitution in miR-10a rs3809783 repressed cell proliferation and migratory capacity. Further investigation discovered that Bcl-2-interacting mediator (Bim) was the functional target of miR-10a and inversely regulated Bim expression. Dual-luciferase assay indicated that A allele in miR-10a rs3809783 could more effectively suppress Bim expression than T allele. In addition, A to T substitution in miR-10a rs3809783 attenuated the sensibility of cells to progesterone and its antagonist mifepristone. Collectively, our data suggest that rs3809783 A > T in pri-miR-10a may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-10a and reinforcing the expression of Bim.


Subject(s)
Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/genetics , Bcl-2-Like Protein 11/metabolism , Biomarkers/analysis , MicroRNAs/genetics , Polymorphism, Single Nucleotide/genetics , Apoptosis , Bcl-2-Like Protein 11/genetics , Blotting, Western , Cell Movement , Cell Proliferation , Cells, Cultured , China/epidemiology , Female , Flow Cytometry , Genetic Predisposition to Disease , Humans , Immunoenzyme Techniques , Pregnancy , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Recurrence , Reverse Transcriptase Polymerase Chain Reaction
18.
Drug Des Devel Ther ; 9: 2089-100, 2015.
Article in English | MEDLINE | ID: mdl-25926719

ABSTRACT

Gliomas are amongst the most insidious and destructive types of brain cancer and are associated with a poor prognosis, frequent recurrences, and extremely high lethality despite combination treatment of surgery, radiotherapy, and chemotherapy. The existence of the blood-brain barrier (BBB) restricts the delivery of therapeutic molecules into the brain and offers the clinical efficacy of many pharmaceuticals that have been demonstrated to be effective for other kinds of tumors. This challenge emphasizes the need to be able to deliver drugs effectively across the BBB to reach the brain parenchyma. Enhancement of the permeability of the BBB and being able to transport drugs across it has been shown to be a promising strategy to improve drug absorption and treatment efficacy. This review highlights the innovative technologies that have been introduced to enhance the permeability of the BBB and to obtain an optimal distribution and concentration of drugs in the brain to treat gliomas, such as nanotechniques, hyperthermia techniques, receptor-mediated transport, cell-penetrating peptides, and cell-mediated delivery.


Subject(s)
Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Blood-Brain Barrier/drug effects , Brain Neoplasms/drug therapy , Drug Delivery Systems , Glioma/drug therapy , Drug Delivery Systems/adverse effects , Humans , Nanotechnology , Permeability/drug effects
19.
PLoS One ; 9(12): e114781, 2014.
Article in English | MEDLINE | ID: mdl-25479352

ABSTRACT

MicroRNAs (miRNAs) are short non-coding RNAs which modulate gene expression by binding to complementary segments present in the 3'UTR of the mRNAs of protein coding genes. MiRNAs play very important roles in maintaining normal human body physiology conditions, meanwhile, abnormal miRNA expressions have been found related to many human diseases spanning from psychiatric disorders to malignant cancers. Recently, emerging reports have indicated that disturbed miRNAs expression contributed to the pathogenesis of recurrent pregnancy loss (RPL). In this study, we identified a new mutation site (+29A>G, position relative to pre-miR-125a) by scanning pri-miR-125a coding region in 389 Chinese Han RPL patients. This site was co-existed with two polymorphisms (rs12976445 and rs41275794) in patients heterogeneously and changed the predicted secondary structures of pri-miR-125a. Subsequent in vitro analysis indicated that the A>G mutation reduced mature miR-125a expression, and further led to less efficient inhibition of verified target genes. Functional analysis showed that mutant pri-mir-125a can enhance endometrial stromal cells (ESCs) invasive capacity and increase the sensitivity of ESCs cells to mifepristone. Moreover, we further analyzed the possible molecular mechanism by RIP-chip assay and found that mutant pri-mir-125a disturbed the expression of miR-125a targetome, the functions of which includes embryonic development, cell proliferation, migration and invasion. These data suggest that A>G mutation in pri-miR-125a coding region contributes to the genetic predisposition to RPL by disordering the production of miR-125a, which consequently meddled in gene regulatory network between mir-125a and mRNA.


Subject(s)
Abortion, Habitual/genetics , MicroRNAs/genetics , Mutation , 3' Untranslated Regions , Asian People/genetics , Case-Control Studies , Cells, Cultured , Endometrium/cytology , Female , Gene Expression Regulation , Genetic Predisposition to Disease , Haplotypes , Humans , MicroRNAs/chemistry , Mifepristone/pharmacology , Polymorphism, Single Nucleotide , Pregnancy , RNA Stability , Stromal Cells/drug effects , Stromal Cells/pathology
20.
Appl Opt ; 53(31): 7402-6, 2014 Nov 01.
Article in English | MEDLINE | ID: mdl-25402905

ABSTRACT

In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.

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