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Publication
Journal: Human Reproduction
September/7/2015
Abstract
OBJECTIVE
Does high mobility group box protein 1 (HMGB1) regulate inflammatory reactions in a rat model of experimental autoimmune orchitis (EAO)?
CONCLUSIONS
HMGB1 appears to be involved in regulating inflammatory reactions in testes, as HMGB1 is translocated from testicular cells during the course of EAO and blocking its action by ethyl pyruvate (EP) reduces disease progression and spermatogenic damage.
BACKGROUND
Despite its immune privileged status, the human testis is prone to inflammatory lesions associated with male factor infertility. Accumulating evidence shows that HMGB1 plays an important role in onset and progression of autoimmune diseases.
METHODS
This is a cross sectional and longitudinal study involving Wistar male rats immunized with testicular homogenates to induce EAO 50 (EAO50; n = 10) and 80 (EAO80; n = 10) days after first immunization. Control adjuvant animals received saline instead of testicular homogenate (n = 16). Untreated animals (n = 10) were also studied. An interventional study was performed to block the action of HMGB1 starting 20 days after first immunization in EAO animals and respective controls (n = 17). Rats were treated i.p. with EP and the effect of EP treatment on testicular pathogenesis was evaluated 30 days later. Moreover, human testicular biopsies from infertile men with focal lymphocytic infiltrates (n = 7) and sections with intact spermatogenesis (n = 6) were probed with antibodies against HMGB1.
METHODS
Testicular RNA and protein extracts from EAO animals, EAO animals treated with EP and relevant controls were used for analysis of cytokine expression by real-time RT-PCR and enzyme-linked immunosorbent assay. HMGB1 was co-localized on rat testicular cross sections with antibodies against testicular macrophages (TM), peritubular cells (PTC) and Sertoli cells (SC). Interaction of HMGB1 and its receptors (RAGE, TLR4) as well signaling pathways after HMGB1 stimulation were studied in isolated TM, PTC and SC by proximity ligation assay and western blot, respectively. Furthermore, HMGB1 immunofluorescence on human testicular biopsies was performed.
RESULTS
HMGB1 was translocated from the nuclei in EAO testes and testes of infertile men with impaired spermatogenesis and lymphocytic infiltrates. Elevated HMGB1 levels were observed during late phase of EAO. In testicular somatic cells HMGB1 receptors Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products (RAGE) were differentially expressed: HMGB1-TLR4 binding was predominant in TM, while HMGB1-RAGE interaction was prevalent in SC and PTC. In support, HMGB1 triggered extracellular signal regulated kinase (ERK)1/2 and cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) activation in SC and PTC, while TM responded to HMGB1 stimulation with p38 mitogen-activated protein kinase (MAPK) and p65 nuclear factor Kappa B (NF-ĸB) phosphorylation followed by increased tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) mRNA levels. In vivo treatment of EAO animals with EP 20 days after induction of disease revealed beneficial effects, as documented by reduced disease progression and spermatogenic damage, lower macrophage numbers, as well as decreased concentrations of HMGB1 and IL-6 in the testis compared with EAO controls.
CONCLUSIONS
The ability of HMGB1 to bind to a wide range of receptors makes it difficult to prevent its action by blockade of a specific receptor; therefore we applied EP, a drug preventing HMGB1 release from cells. Due to its mode of action EP decreases also the secretion of some other pro-inflammatory cytokines. Using isolated primary cells imposes limitations for cell transfection studies. As a compromise between purity and yield primary cells need to be isolated from animals of different age, which has to be considered when comparing their responses.
CONCLUSIONS
HMGB1 could be a promising target in attenuating testicular damage caused by inflammatory reactions.
Publication
Journal: Public Health Nutrition
January/25/2006
Abstract
OBJECTIVE
To investigate the prevalence of anaemia and iron deficiency and vitamin A status among school-aged children in rural Kazakhstan and identify factors associated with anaemia in this population.
METHODS
A cross-sectional design.
METHODS
School-aged children in rural Kazakhstan.
METHODS
Socio-economic and anthropometric information was collected from 159 school-aged children living in the Kzyl-Orda region of Kazakhstan. Blood samples were collected and the concentrations of haemoglobin (Hb), serum iron, serum ferritin (SF), erythrocyte protoporphyrin (EP), serum retinol and beta-carotene, total iron binding capacity (TIBC), transferrin saturation (TS) and other haematological indices were measured.
RESULTS
Among the 159 children, the prevalence of anaemia and iron deficiency defined by the multiple criteria model (SF, TS and EP) was 27% and 13%, respectively. Nine per cent had iron-deficiency anaemia and 21% had serum retinol value < 1.05 micromol l(-1). Mean SF and serum iron concentrations and TS were significantly lower in anaemic children than in their non-anaemic peers, while TIBC and EP were significantly higher in children with anaemia. Hb was significantly correlated with serum iron and retinol concentrations. Serum retinol and SF concentrations and mean corpuscular volume were significantly correlated with Hb by multiple regression analysis.
CONCLUSIONS
Anaemia among school-aged children in rural Kazakhstan appears to be related to iron indices and vitamin A status.
Publication
Journal: Journal of Clinical and Diagnostic Research
September/21/2015
Abstract
OBJECTIVE
The present study was aimed to investigate the antibiotic resistance, virulence potential and phylogenetic grouping of ESBL-producing uropathogenic Escherichia coli (EP-UPEC) isolated from long-term hospitalized patients.
METHODS
EP-UPEC isolates from September 2013 to June 2014 at a tertiary care hospital of China were screened for ESBL-production by the double disk diffusion test. Isolates with ESBL-phenotype were further characterized by antibiotic resistance testing, PCR of different ESBL and virulence genes, and phylogenetic grouping.
RESULTS
One hundred and twenty EP-UPEC were isolated from long-term hospitalized patients. All EP-UPEC isolates were resistant to Ampicillin, Cefazolin, Cefuroxime, Cefotaxime, Cefoperazone and Ceftriaxone, and the majority of EP-UPEC isolates were resistant to Piperacillin (82.5%), Ciprofloxacin (81.2%), Trimethoprim-Sulfamethoxazole (72.5%). The isolates showed the highest sensitivity against Imipenem (98.4%), Piperacillin/tazobactam (96.7%), Cefoperazone/sulbactam (91.7%), Amikacin (90.8%) and Cefepime (75.8%). Nine different ESBL genotype patterns were observed and CTX-M type was the most prevalent ESBL genotype (42.5%, 51/120). Majority of EP-UPEC isolates possess more than one ESBL genes. EP-UPEC isolates belonged mainly to phylogenetic group B2(36.7%) and D(35.0%). The prevalence of traT, ompT, iss, PAI, afa, fimH and papC were 75.8%, 63.3%, 63.3%, 60.8%, 40.8%, 19.2% and 6.7%, respectively. The number of virulence genes (VGs) detected was significantly higher in group B2 than in group A (ANOVA, p<0.001), group B1(ANOVA, p= 0.012) and D (ANOVA, p<0.001).
CONCLUSIONS
EP-UPEC strains showed multidrug resistance and co-resistance to other non β-lactam antibiotics. CTX-M was the most prevalent ESBL genotype and majority of EP-UPEC strains more than one ESBL genes. EP-UPEC strains belonged mainly to phylogenetic group B2 and D, and most of the virulence genes were more prevalent in group B2.
Publication
Journal: PLoS ONE
July/24/2016
Abstract
The administration of fructooligosaccharides (FOS) beneficially modulates gastrointestinal functions and may enhance the metabolism of polyphenols. However, different polyphenolic components in the diet may have different influences on the activities of the digestive enzymes and microbiota in the gastrointestinal tract. Therefore, a 4-week study of forty-eight male Wistar rats was conducted to investigate the physiological response of the rat cecal environment to diets without and with FOS that contained two different strawberry polyphenolic extracts, specifically EP (polyphenolic profile 60, 35, 5, and 0% ellagitannins, proanthocyanidins, flavonols, anthocyanins, respectively) and EPA (polyphenolic profile: 50, 35, 6, and 9%, respectively). When combined with FOS, both extracts beneficially enhanced the acidification of the cecal digesta (P≤0.05 vs the groups without extracts), but the dietary combination of EPA and FOS elicited the greatest reduction in putrefactive short-chain fatty acid production and the lowest fecal β-glucuronidase activity in the cecum (P≤0.05 vs group EP). Moreover, the addition of dietary FOS elevated the metabolism of the examined strawberry extracts in the cecum and thereby increased the concentrations of the metabolites in the cecal digesta and urine (P≤0.05 vs the group with cellulose). Overall, both strawberry extracts modulated the effects of FOS in the gastrointestinal tract; however, the combination with EPA extract that contained anthocyanins exhibited greater beneficial effects in the lower gut environment than the EP extract.
Publication
Journal: ACS Nano
October/4/2019
Abstract
Periodontitis is a common disease caused by plaque biofilms, which are important pathogenic factors of many diseases and may be eradicated by antibiotic therapy. However, low dose antibiotic therapy is a complicated challenge for eradiating biofilms as hundreds (even thousands) of times higher concentrations of antibiotics are needed than killing planktonic bacteria. Polymer vesicles may solve these problems via effective antibiotic delivery into biofilms, but traditional single corona vesicles lack the multifunctionalities essential for biofilm eradication. In this paper, we aim to effectively treat biofilm-induced periodontitis using much lower concentrations of antibiotics than traditional antibiotic therapy by designing a multifunctional dual corona vesicle with intrinsic antibacterial and enhanced antibiotic delivery capabilities. This vesicle is co-assembled from two block copolymers, poly(ε-caprolactone)-block-poly(lysine-stat-phenylalanine) [PCL-b-P(Lys-stat-Phe)] and poly(ethylene oxide)-block-poly(ε-caprolactone) [PEO-b-PCL]. Both PEO and P(Lys-stat-Phe) coronas have their specific functions: PEO endows vesicles with protein repelling ability to penetrate extracellular polymeric substances (EPS) in biofilms ('stealthy' coronas), while P(Lys-stat-Phe) provides vesicles with positive charges and broad spectrum intrinsic antibacterial activity. As a result, the dosage of antibiotics can be reduced by 50% when encapsulated in the dual corona vesicles to eradicate Escherichia coli (E. coli) or Staphylococcus aureus (S. aureus) biofilms. Furthermore, effective in vivo treatment has been achieved from a rat periodontitis model, as confirmed by significantly reduced dental plaque, and alleviated inflammation. Overall, this 'stealthy' and antibacterial dual corona vesicle demonstrates a fresh insight for improving the antibiofilm efficiency of antibiotics and combating the serious threat of biofilm-associated diseases.
Publication
Journal: Journal of Applied Physiology
April/29/2007
Abstract
It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.
Publication
Journal: Brain Research
June/11/1996
Abstract
The effects of two intensities of formalin pain on behaviour and beta-Endorphin (beta-EP) concentration in the brain and pituitary were studied in male and female rats. The animals were familiarized with the Hole-Board apparatus for 3 days, and then, after a subcutaneous injection of formalin (50 microliter, 0.1 or 10%) or Sham-injection (Control) in the hindpaw, they were tested in the Hole-Board for 60 min. Licking, Flexing and Paw-Jerk of the injected limb were recorded. beta-EP concentration was determined in the hypothalamus (HYP), the periaqueductal gray matter (PAG), the anterior pituitary (AP) and the neurointermediate lobe (NIL). Licking and Flexing durations were greater in females than males only with formalin 10%. Sex differences in beta-EP concentration between the Control groups were found in all tissues except the HYP; beta-EP levels were higher in females in the PAG and NIL, but greater in the AP in males. beta-EP concentration increased in males in the HYP and NIL with formalin 10%; in females, a decrease was found in the HYP with formalin 0.1%. The present results suggest that: (a) there are differences between males and females in the responses to formalin pain, and the nature (pattern and duration) of the sex differences varies according to the pain intensity; (b) there are differences in beta-EP concentration between the two sexes in control animals, and male and female rats also exhibit differences in the modifications of beta-EP in response to formalin-induced pain.
Publication
Journal: Applied Microbiology and Biotechnology
May/28/2007
Abstract
Extracellular matrix provides an architectural structure and mechanical stability for aerobic granules. Distributions of cells and extracellular polymeric substances (EPS), including proteins, alpha- and beta-D-glucopyranose polysaccharides, in acetate-fed granules and phenol-fed granules were probed using a novel quadruple staining scheme. In acetate-fed granules, protein and beta-D-glucopyranose polysaccharides formed the core, whereas, the cells and alpha-D-glucopyranose polysaccharides accumulated in the granule outer layers. Based on these experimental findings, this study indicated that different conclusions can be obtained regarding EPS distributions when granules were stained differently. The core of phenol-fed granules, conversely, was formed principally by proteins; whereas, the cells and alpha- and beta-D-glucopyranose polysaccharides were accumulated at an outer filamentous layer. Using a series of confocal laser scanning microscope (CLSM) images whose threshold values were determined via Otsu's scheme, the three-dimensional distributions of cells and EPS were produced using a polygonal surface model. Structural information extracted can be applied in further development of comprehensive granule models.
Publication
Journal: Proceedings of the National Academy of Sciences of the United States of America
June/23/2017
Abstract
Cyclic dimeric GMP (c-di-GMP) has emerged as a key regulatory player in the transition between planktonic and sedentary biofilm-associated bacterial lifestyles. It controls a multitude of processes including production of extracellular polysaccharides (EPSs). The PilZ domain, consisting of an N-terminal "RxxxR" motif and a β-barrel domain, represents a prototype c-di-GMP receptor. We identified a class of c-di-GMP-responsive proteins, represented by the AraC-like transcription factor CuxR in plant symbiotic α-proteobacteria. In Sinorhizobium meliloti, CuxR stimulates transcription of an EPS biosynthesis gene cluster at elevated c-di-GMP levels. CuxR consists of a Cupin domain, a helical hairpin, and bipartite helix-turn-helix motif. Although unrelated in sequence, the mode of c-di-GMP binding to CuxR is highly reminiscent to that of PilZ domains. c-di-GMP interacts with a conserved N-terminal RxxxR motif and the Cupin domain, thereby promoting CuxR dimerization and DNA binding. We unravel structure and mechanism of a previously unrecognized c-di-GMP-responsive transcription factor and provide insights into the molecular evolution of c-di-GMP binding to proteins.
Publication
Journal: International Journal of Biological Macromolecules
September/26/2018
Abstract
A strain Leuconostoc citreum B-2 was isolated from homemade fermentation product of pineapple and its polysaccharide yield was 28.3g/L after cultivating the strain in Man-Rogosa-Sharpe (MRS) medium with 75g/L sucrose. The exopolysaccharide (EPS) was characterized by gas chromatography (GC), Fourier-transform infrared (FT-IR) spectra, high-performance size-exclusion chromatography (HPSEC), nuclear magnetic resonance (NMR) spectroscopy and scanning electron microscope (SEM) analysis in present study. The monosaccharide composition of EPS was glucose and molecular weight was 3.77×106Da. FT-IR and NMR spectra revealed that the B-2 EPS was composed of 75% α-(1→6) linked d-glucopyranose units existing in the main chain with 19% α-(1→3) branching and only a few α-(1→2) branching. The SEM of the dried EPS appeared irregular sheets with glittering surface and compact structure. Water solubility index and water holding capacity of B-2 EPS were 80% and 450%, respectively. All the mentioned characteristics suggested that the EPS has a potential application in the food, cosmetic and pharmaceuticals industry.
Publication
Journal: Biochemical and Biophysical Research Communications
February/24/2015
Abstract
Osteoarthritis (OA) is a progressive joint disorder, which remains the leading cause of chronic disability in aged people. This study is the first report which demonstrates the cartilage protective effect of 5,7,3',4'-tetramethoxyflavone (TMF) by decreasing the concentration of IL-1β, TNF-α and PGE2 in the knee synovial fluid in OA rat models in vivo. In vitro, after induced by PGE2, the apoptosis rate of chondrocytes was significantly increased. In addition, PGE2 increased the expression of cAMP/PKA signaling pathway in chondrocytes, stabilized and accumulated β-catenin, and activated the expression of β-catenin signaling pathway. These activities were counteracted by TMF dose-dependently. Collectively, TMF is a potential compound with chondroprotective activity by inhibiting both EP/cAMP/PKA signaling pathway and β-catenin signaling pathway.
Publication
Journal: Journal of Bioscience and Bioengineering
July/8/2009
Abstract
For substantial cell growth and exopolysaccharide (EPS) production of Bifidobacterium longum JBL05, anaerobic conditions (dissolved oxygen concentrations below 0.05 ppm) and the supplement of CO2 >> or = 20%) were required. Under these conditions, B. longum JBL05 produced EPS amounts of up to 2.9 g/l.
Publication
Journal: PLoS ONE
June/6/2016
Abstract
The objective of the present study was to investigate the role of high-mobility group box-1 (HMGBBL/6 mice were divided into four groups: normal saline control (NS) group, KA-induced epileptic seizure (EP) group, and EP group pretreated with HMGBEP+HMGBBoxA (HMGBEP+BoxA group). Compared to the NS group, increased levels of HMGBEP group. Injection of HMGBBoxA abolished this up-regulation. Next, the regulatory role of HMGBBBBBB (NF-κB) inhibitor], or vehicle. Treatment with HMGBB in bEnd.3 cells. These effects were inhibited by the pre-treatment with either LPS-RS or FPS-ZM1, and were abolished by the pre-treatment of SN50 or a combination treatment of both LPS-RS and FPS-ZM1. Luciferase reporter assays showed that exogenous expression of NF-κB p65 increased the promoter activity of multidrug resistance 1a (P-gp-encoding gene) in endothelial cells. These data indicate that HMGBB in brain microvascular endothelial cells.
Publication
Journal: Veterinary Journal
February/7/2013
Abstract
Equine piroplasmosis (EP) has not been considered indigenous in The Netherlands. However, following the detection of an apparently indigenous subclinical Babesia caballi infection in a horse on Schouwen-Duiveland (an island in the Zeeland Province), a survey was undertaken between May and September 2010 to assess the prevalence of the causative agents of EP in the South-West of The Netherlands. Blood samples from 300 randomly selected horses were tested for specific antibodies against Theileria equi and B. caballi using an indirect fluorescence antibody test (IFAT), and for parasite DNA using a specific polymerase chain reaction combined with reverse line blotting (PCR-RLB). Twelve of the horses (4%) were seropositive for EP. Of these, nine (75%) were positive (titre⩾1:160) for B. caballi alone and three (25%) were also positive for T. equi. PCR-RLB detected T. equi DNA in five horses (1.6%), two of which were seronegative. Four (1.3%) of the positive horses (three positive for T. equi and one for both B. caballi and T. equi) were considered truly indigenous. During the study, two indigenous ponies from a farm situated outside the sampling area were diagnosed with acute clinical piroplasmosis characterized by severe anaemia and pyrexia. Blood smears showed T. equi - like inclusions in red blood cells, and T. equi infection was confirmed in both ponies by PCR-RLB. The initial subclinical B. caballi infection, the survey results and the two acute clinical EP cases confirmed the autochthonous transmission of B. caballi and T. equi infections in The Netherlands.
Publication
Journal: BMC Microbiology
June/5/2017
Abstract
Bacteroides fragilis is the most frequent species at the human intestinal mucosal surface, it contributes to the maturation of the immune system although is also considered as an opportunistic pathogen. Some Bifidobacterium strains produce exopolysaccharides (EPS), complex carbohydrate polymers that promote changes in the metabolism of B. fragilis when this microorganism grows in their presence. To demonstrate that B. fragilis can use EPS from bifidobacteria as fermentable substrates, purified EPS fractions from two strains, Bifidobacterium longum E44 and Bifidobacterium animalis subsp. lactis R1, were added as the sole carbon source in cultures of B. fragilis DSMZ 2151 in a minimal medium. Bacterial counts were determined during incubation and the evolution of organic acids, short chain fatty acids (SCFA) and evolution of EPS fractions was analysed by chromatography.
Growth of B. fragilis at early stages of incubation was slower in EPS than with glucose, microbial levels remaining higher in EPS at prolonged incubation times. A shift in metabolite production by B. fragilis occurred from early to late stages of growth, leading to the increase in the production of propionate and acetate whereas decrease lactate formation. The amount of the two peaks with different molar mass of the EPS E44 clearly decreased along incubation whereas a consumption of the polymer R1 was not so evident.
This report demonstrates that B. fragilis can consume some EPS from bifidobacteria, with a concomitant release of SCFA and organic acids, suggesting a role for these biopolymers in bacteria-bacteria cross-talk within the intestine.
Publication
Journal: Journal of Neuroscience
July/23/2017
Abstract
Studies of the effect of hormone therapy on cognitive function in menopausal women have been equivocal, in part due to differences in the type and timing of hormone treatment. Here we cognitively tested aged female rhesus macaques on (1) the delayed response task of spatial working memory, (2) a visuospatial attention task that measured spatially and temporally cued reaction times, and (3) a simple reaction time task as a control for motor speed. After task acquisition, animals were ovariectomized (OVX). Their performance was compared with intact controls for 2 months, at which time no group differences were found. The OVX animals were then assigned to treatment with either a subcutaneous sham implant (OVX), 17-β estradiol (E) implant (OVX+E) or E implant plus cyclic oral progesterone (OVX+EP). All groups were then tested repeatedly over 12 months. The OVX+E animals performed significantly better on the delayed response task than all of the other groups for much of the 12 month testing period. The OVX+EP animals also showed improved performance in the delayed response task, but only at 30 s delays and with performance levels below that of OVX+E animals. The OVX+E animals also performed significantly better in the visuospatial attention task, particularly in the most challenging invalid cue condition; this difference also was maintained across the 12 month testing period. Simple reaction time was not affected by hormonal manipulation. These data demonstrate that chronic, continuous administration of E can exert multiple beneficial cognitive effects in aged, OVX rhesus macaque females.
Hormone therapy after menopause is controversial. We tested the effects of hormone replacement in aged rhesus macaques, soon after surgically-induced menopause [ovariectomy (OVX)], on tests of memory and attention. Untreated ovarian-intact and OVX animals were compared with OVX animals receiving estradiol (E) alone or E with progesterone (P). E was administered in a continuous fashion via subcutaneous implant, whereas P was administered orally in a cyclic fashion. On both tests, E-treated animals performed better than the other 3 experimental groups across 1 year of treatment. Thus, in this monkey model, chronic E administered soon after the loss of ovarian hormones had long-term benefits for cognitive function.
Publication
Journal: Molecular Cancer Research
September/15/2015
Abstract
Understanding the molecular mechanisms behind formation of melanoma, the deadliest form of skin cancer, is crucial for improved diagnosis and treatment. One key is to better understand the cross-talk between epidermal keratinocytes and pigment-producing melanocytes. Here, using a bigenic mouse model system combining mutant oncogenic NRAS(Q61K) (constitutively active RAS) or mutant activated CDK4(R24C/R24C) (prevents binding of CDK4 by kinase inhibitor p16(INK4A)) with an epidermis-specific knockout of the nuclear retinoid X receptor alpha (RXRα(ep-/-)) results in increased melanoma formation after chronic ultraviolet-B (UVB) irradiation compared with control mice with functional RXRα. Melanomas from both groups of bigenic RXRα(ep-/-) mice are larger in size with higher proliferative capacity, and exhibit enhanced angiogenic properties and increased expression of malignant melanoma markers. Analysis of tumor adjacent normal skin from these mice revealed altered expression of several biomarkers indicative of enhanced melanoma susceptibility, including reduced expression of tumor suppressor p53 and loss of PTEN, with concomitant increase in activated AKT. Loss of epidermal RXRα in combination with UVB significantly enhances invasion of melanocytic cells to draining lymph nodes in bigenic mice expressing oncogenic NRAS(Q61K) compared with controls with functional RXRα. These results suggest a crucial role of keratinocytic RXRα to suppress formation of UVB-induced melanomas and their progression to malignant cancers in the context of driver mutations such as activated CDK4(R24C/R24C) or oncogenic NRAS(Q61K).
CONCLUSIONS
These findings suggest that RXRα may serve as a clinical diagnostic marker and therapeutic target in melanoma progression and metastasis.
Publication
Journal: Radiographics
December/11/2018
Abstract
Encapsulating peritoneal sclerosis (EPS) is a rare but serious condition that results in (a) encapsulation of bowel within a thickened fibrocollagenous peritoneal membrane and (b) recurrent episodes of bowel obstruction. Although described by various names in the literature, the preferred term is encapsulating peritoneal sclerosis because it best describes the morphologic and histologic changes in this disorder. The etiology of EPS is multifactorial, with a wide variety of implicated predisposing factors that disrupt the normal physiologic function of the peritoneal membrane-prime among these factors being long-term peritoneal dialysis and bacterial peritoneal infections, especially tuberculosis. The clinical features of EPS are usually nonspecific, and knowledge of the radiologic features is necessary to make a specific diagnosis. The findings on radiographs are usually normal. Images from small-bowel follow-through studies show the bowel loops conglomerated in a concertina-like fashion with a serpentine arrangement in a fixed U-shaped configuration. US demonstrates a "cauliflower" appearance of bowel with a narrow base, as well as a "trilaminar" appearance depicted especially with use of high-resolution US probes. CT is the imaging modality of choice and allows identification of the thickened contrast material-enhanced abnormal peritoneal membrane and the encapsulated clumped bowel loops. In addition, CT can potentially help identify the cause of EPS (omental granuloma in tuberculosis), as well as the complications of EPS (bowel obstruction). Conservative medical treatment and surgical therapy early in the course of EPS have been used for management of the condition. The purpose of this article is to review the nomenclature and etiopathogenesis of EPS, describe the multimodality imaging appearances of EPS, including differentiating its features from those of other conditions mimicking EPS, and give an overview of management options. Online DICOM image stacks are available for this article. ©RSNA, 2018.
Publication
Journal: Applied Biochemistry and Biotechnology
February/28/2021
Abstract
α-amylase is known to have antibiofilm activity against biofilms of both Gram positive and Gram-negative bacterial strains. Partially purified α-amylase from Bacillus subtilis was found to have inhibit biofilm formed by P. aeruginosa and S. aureus. The spectrophotometric and microscopic studies revealed that the antibiofilm efficacy of the working strain is greater than commercially purchased α-amylase. Response surface methodology (RSM) and artificial neural network (ANN) help to predict the optimum conditions [pH 8, treatment time 6 h and enzyme concentration (200 µg/mL)] for maximum biofilm eradication. This was confirmed by several in vitro experiments. Molecular docking interactions of α-amylase with the extracellular polymeric substances (EPS) of both P. aeruginosa and S. aureus indicate towards the existence of an efficient energy driven spontaneous process. Thus, this study highlights a combination of experimental and computational approach showing the naturally extracted α-amylase from B. subtilis having the potency of removing the biofilms of harmful bacterial strains involved in causing various nosocomial infections.
Keywords: Antibiofilm; Bacillus subtilis; Biofilm; Pseudomonas aeruginosa; Staphylococcus aureus; α-amylase.
Publication
Journal: Journal of Pediatrics
March/22/2010
Abstract
OBJECTIVE
To assess the biophysical properties of the aorta in children born small for gestational age (SGA) with an echo-Doppler method and to determine associations with known perinatal risk factors.
METHODS
In this cross-sectional study, 39 SGA and 41 control subjects aged 8 to 13 years were recruited. Perinatal risk factors were recorded. The aortic diameters and pulse wave transit time around the aortic arch were measured with echo-Doppler and the blood pressure recorded. Pulse wave velocity, aortic input impedance (Zi), characteristic impedance (Zc), arterial pressure-strain elastic modulus (Ep), and arterial wall stiffness index (beta-index) were calculated.
RESULTS
Pulse wave velocity (374 +/- 46 vs 348 +/- 47 cm/sec, P < .02); Zi (177 +/- 39 vs 142 +/- 27 dynes x sec/cm(5), P < .0001); Zc (185 +/- 29 vs 152 +/- 37 dynes x sec/cm(5), P < .0001); Ep (286 +/- 101 vs 216 +/- 41 mm Hg, P < .0001); and beta-index (2.43 +/- 0.32 vs 2.17 +/- 0.15, P < .0001) were all higher in SGA. We found negative associations between the following: birth weight and Zi, Zc, Ep, and beta-index; as well as body mass index and Zi, Zc.
CONCLUSIONS
This simple echo-Doppler method demonstrated abnormal biophysical properties of the aorta in a cohort of pre-adolescent patients born SGA who remain small in stature and continue to have normal blood pressure.
Publication
Journal: Clinical Cancer Research
October/4/2019
Abstract
Interleukin-12 (IL-12) promotes adaptive type-1 immunity and has demonstrated anti-tumor efficacy, but systemic administration leads to severe adverse events (AEs), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL-12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.Fifteen MCC patients with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (Cohort A, N=3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (Cohort B, N=12) received up to 4 cycles total, administered at least six weeks apart. Serial tumor and blood samples were collected.All patients successfully completed at least one cycle with transient, mild (Grade 1, 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL-12 protein was observed along with local inflammation and increased tumor-specific CD8+ T cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in Cohort B, with two patients experiencing durable clinical benefit (16 and 55+ months respectively). Two Cohort A patients (one with pathologic complete remission) were recurrence-free at 44+ and 75+ months.I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL-12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer.
Publication
Journal: Journal of Ethnopharmacology
September/18/2019
Abstract
<A<em>b</em>stractText>Musa acuminata, a tropical plant <em>b</em>elongs to the family Musaceae. The fruit peels of this plant have <em>b</em>een well documented for their therapeutic value in Asia and Africa. It has also <em>b</em>een previously reported for numerous <em>b</em>iological applications such as antimicro<em>b</em>ial, antioxidant, itching, psoriasis and anti-diarrheal activities. Moreover, M. acuminata peels have <em>b</em>een well known for its anti-healing and antiseptic properties and most commonly used for healing wounds and heat <em>b</em>urns in South Asian and African traditional medicines.</A<em>b</em>stractText><A<em>b</em>stractText>To evaluate the QS-mediated anti<em>b</em>iofilm and antivirulence potential of M. acuminata, and its <em>b</em>ioactive meta<em>b</em>olites 5-Hydroxymethylfurfural (5HMF) against Pseudomonas aeruginosa.</A<em>b</em>stractText><p><div>(<em>b</em>)MATERIALS AND METHODS</<em>b</em>)</div>The M. acuminata peel methanol extract (MAM) was evaluated for its anti<em>b</em>iofilm potential against P. aeruginosa with increasing concentration. Besides, <em>b</em>iofilm related phenomenon's such as total <em>b</em>iofilm proteins, microcolony formation exopolysaccharides (<em>EPS</em>) and cell surface hydropho<em>b</em>icity (CSH) productions were also examined to support the anti<em>b</em>iofilm potential of MAM. Further, MAM was evaluated for its antivirulence efficacy against P. aeruginosa <em>b</em>y assessing the protease, LasA protease, LasB elastase, pyocyanin, alginate and rhamnolipid productions at 400 μg ml<sup>-1</sup> concentration. Transcriptional analysis of QS regulated virulence genes expression level was also done <em>b</em>y real-time PCR analysis. Then, the MAM was su<em>b</em>jected to column chromatography for further fractions and the <em>b</em>ioactive compounds present in MAM were identified <em>b</em>y gas chromatograph-mass spectrometry analysis. Further, the major compounds such as 5-hydroxymethylfurfural, vaccenic acid and pentanoic acid identified from active fraction of MAM were evaluated for their anti<em>b</em>iofilm and antivirulence potential against P. aeruginosa.</p><p><div>(<em>b</em>)RESULTS</<em>b</em>)</div>MAM significantly inhi<em>b</em>ited the <em>b</em>iofilm formation in P. aeruginosa at 400 μg ml<sup>-1</sup> concentration which also inhi<em>b</em>ited the production of <em>b</em>iofilm proteins, <em>b</em>iofilm adherence, <em>EPS</em> and CSH productions to the level of 79%, 82% and 77% respectively. Further, the antivirulence potential was confirmed through numerous virulence inhi<em>b</em>ition assays. The MAM at 400 μg ml<sup>-1</sup> concentration inhi<em>b</em>ited the QS-mediated virulence production such as protease, LasA protease, LasB elastase, pyocyanin, alginate and rhamnolipid productions to the level of 77%, 75%, 68%, 80%, 78% and 69% respectively. Moreover, the results of qPCR analysis confirmed the downregulation of QS regulated virulence genes expression upon treatment with MAM. The chromatographic analysis revealed the presence of 5-Hydroxymethylfurfural (5HMF), vaccenic acid and pentanoic acid in MAM and the potential <em>b</em>ioactive compounds with anti<em>b</em>iofilm and antivirulence was identified as 5-hydroxymethylfurfural, without exerting any growth inhi<em>b</em>ition in P. aeruginosa.</p><A<em>b</em>stractText>This study investigated the ideal anti<em>b</em>iofilm and antivirulence potential of MAM and its <em>b</em>ioactive compound 5HMF, and confirms the ethnopharmacological value of these peels against P. aeruginosa infections.</A<em>b</em>stractText>
Publication
Journal: Accident Analysis and Prevention
January/11/2019
Abstract
<A<em>b</em>stractText>A novel <em>b</em>icycle helmet concept has <em>b</em>een developed to mitigate rotational head acceleration, which is a predominant mechanism of traumatic <em>b</em>rain injury (TBI). This WAVECEL concept employs a collapsi<em>b</em>le cellular structure that is recessed within the helmet to provide a rotational suspension. This cellular concept differs from other <em>b</em>icycle helmet technologies for mitigation of rotational head acceleration, such as the commercially availa<em>b</em>le Multi-Directional Impact Protection System (MIPS) technology which employs a slip liner to permit sliding <em>b</em>etween the helmet and the head during impact. This study quantified the efficacy of <em>b</em>oth, the WAVECEL cellular concept, and a MIPS helmet, in direct comparison to a traditional <em>b</em>icycle helmet made of rigid expanded polystyrene (<em>EPS</em>).</A<em>b</em>stractText><A<em>b</em>stractText>Three <em>b</em>icycle helmet types were su<em>b</em>jected to o<em>b</em>lique impacts in guided vertical drop tests onto an angled anvil: traditional <em>EPS</em> helmets (CONTROL group); helmets with a MIPS slip liner (SLIP group); and helmets with a WAVECEL cellular structure (CELL group). Helmet performance was evaluated using 4.8 m/s impacts onto anvils angled at 30°, 45°, and 60° from the horizontal plane. In addition, helmet performance was tested at a faster speed of 6.2 m/s onto the 45° anvil. Five helmets were tested under each of the four impact conditions for each of the three groups, requiring a total of 60 helmets. Headform kinematics were acquired and used to calculate an injury risk criterion for A<em>b</em><em>b</em>reviated Injury Score (AIS) 2 <em>b</em>rain injury.</A<em>b</em>stractText><p><div>(<em>b</em>)RESULTS</<em>b</em>)</div>Linear acceleration of the headform remained <em>b</em>elow 90 g and was not associated with the risk of skull fracture in any impact scenario and helmet type. Headform rotational acceleration in the CONTROL group was highest for 6.2 m/s impacts onto the 45° anvil (7.2 ± 0.6 krad/s<sup>2</sup>). In this impact scenario, SLIP helmets and CELL helmets reduced rotational acceleration <em>b</em>y 22% (p = 0003) and 73% (p < 0.001), respectively, compared to CONTROL helmets. The CONTROL group had the highest AIS 2 <em>b</em>rain injury risk of 59 ± 8% for 6.2 m/s impacts onto the 45° anvil. In this impact scenario, SLIP helmets and CELL helmets reduced the AIS 2 <em>b</em>rain injury risk to 34.2% (p = 0.001) and 1.2% (p < 0.001), respectively, compared to CONTROL helmets.</p><A<em>b</em>stractText>Results of this study are limited to a narrow range of impact conditions, <em>b</em>ut demonstrated the potential that rotational acceleration and the associated <em>b</em>rain injury risk can <em>b</em>e significantly reduced <em>b</em>y the cellular WAVECEL concept or a MIPS slip liner. Results o<em>b</em>tained under specific impact angles and impact velocities indicated performance differences <em>b</em>etween these mechanisms. These differences emphasize the need for continued research and development efforts toward helmet technologies that further improve protection from <em>b</em>rain injury over a wide range a realistic impact parameters.</A<em>b</em>stractText>
Publication
Journal: Indian Journal of Pediatrics
July/18/2000
Abstract
In order to examine the prevalence of lead exposure and iron deficiency in Jammu, blood lead (B-Pb) and erythrocyte protoporphyrin (EP-ZnPP) levels were measured in a group of 125 children and compared with B-Pb and EP levels of 46 New Delhi children. The mean B-Pb level of Jammu children was 15 micrograms/dl and ZnPP level 46 micrograms/dl. The frequency distribution of B-Pb in Jammu children according to the 1997 CDC stratification showed that only 33% were below the 10 micrograms/dl "normal" threshold levels and 50.5% were between 10-19 micrograms/dl, an increasing level of concern. The remaining 16.5% were in the medical intervention lead poisoned level between 20-87 micrograms/dl with corresponding EP levels between 29-160 micrograms/dl. The mean B-Pb and ZnPP levels for New Delhi children were 14 micrograms/dl and 55 micrograms/dl respectively. This study on Jammu children shows a modest increase in mean B-Pb and EP levels from those in 1985; the percentage of children with higher levels of B-Pb>> 10 micrograms/dl have significantly increased. Moreover, the continued underlying high prevalence of iron deficiency among these children predisposes them to increased lead absorption from various sources thus aggravating further, the detrimental effects of lead. Therefore, a more extensive screening of all children below 10 years of age and an ongoing B-Pb and EP monitoring and iron supplementation programme for Jammu and New Delhi is essential. An environmental assessment of the sources leading to serious lead intoxication problem in Jammu, a rapidly growing and overpopulated city of the state of Jammu and Kashmir is strongly recommended.
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