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1.
World Neurosurg X ; 22: 100303, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38510336

ABSTRACT

Large-vessel occlusion (LVO) stroke is a promising field for the use of AI, especially machine learning (ML) because optimal results are highly dependent on timely diagnosis, communication, and treatment. In order to better understand the current state of artificial intelligence (AI) in relation to LVO strokes, its efficacy, and potential future applications, we searched relevant literature to perform a comprehensive evaluation of the topic. The databases PubMed, Embase, and Scopus were extensively searched for this review. Studies were then screened using title and abstract criteria and duplicate studies were excluded. By using pre-established inclusion and exclusion criteria, it was decided whether or not to include full-text papers in the final analysis. The studies were analyzed, and the relevant information was retrieved. In recognizing LVO on computed tomography, ML approaches were very accurate. There is a shortage of AI applications for thrombectomy patient selection, despite the fact that certain research accurately evaluates individual patient eligibility for endovascular therapy. Machine learning algorithms may reasonably predict clinical and angiographic outcomes as well as associated factors. AI has shown promise in the diagnosis and treatment of people who have just suffered a stroke. However, the usefulness of AI in management and forecasting remains restricted, necessitating more studies into machine learning applications that can guide decision making in the future.

2.
Indian J Gastroenterol ; 42(1): 32-39, 2023 02.
Article in English | MEDLINE | ID: mdl-36656484

ABSTRACT

BACKGROUND: Functional gastrointestinal disorders (FGIDs), including irritable bowel syndrome (IBS), are associated with psychological abnormalities, such as anxiety and depression. Though the data on this are plenty in global literature, Indian data are sparse. We performed a systematic review and meta-analysis of Indian data on anxiety and depression among patients with IBS to estimate their pooled prevalence and to identify the shortcomings so that future areas of research can be identified. METHOD: A comprehensive literature search was performed for studies applying tests for psychological issues in patients with IBS. After applying prospectively decided exclusion criteria, the eligible papers were examined using a meta-analysis approach for the prevalence of anxiety and depression in IBS patients using different tests. The odds ratios (OR) of anxiety and depression among subjects with IBS were calculated compared to controls. RESULTS: Of seven studies (590 IBS patients and 1520 controls) included in the meta-analysis, the pooled OR of anxiety was 8.060 (95% confidence interval [CI] 4.007-16.213) as compared to controls (random-effect model). The pooled OR of depression was 7.049 (95% CI 3.281-15.147) compared to controls (random-effect model). There was significant heterogeneity in the included studies. CONCLUSION: The current meta-analysis shows that the patients with IBS from India have eightfold greater risks of anxiety and sevenfold greater risks of depression than the controls. However, most of these data were from tertiary urban centers, and hence, there might be recruitment bias over-estimating the frequency.


Subject(s)
Anxiety , Depression , Irritable Bowel Syndrome , Humans , Anxiety/epidemiology , Anxiety/etiology , Asian People , Depression/epidemiology , Depression/etiology , Irritable Bowel Syndrome/epidemiology , Irritable Bowel Syndrome/complications
3.
Biomedicines ; 10(9)2022 Aug 23.
Article in English | MEDLINE | ID: mdl-36140156

ABSTRACT

The low water solubility of pharmacoactive molecules limits their pharmacological potential, but the solubility parameter cannot compromise, and so different approaches are employed to enhance their bioavailability. Pharmaceutically active molecules with low solubility convey a higher risk of failure for drug innovation and development. Pharmacokinetics, pharmacodynamics, and several other parameters, such as drug distribution, protein binding and absorption, are majorly affected by their solubility. Among all pharmaceutical dosage forms, oral dosage forms cover more than 50%, and the drug molecule should be water-soluble. For good therapeutic activity by the drug molecule on the target site, solubility and bioavailability are crucial factors. The pharmaceutical industry's screening programs identified that around 40% of new chemical entities (NCEs) face various difficulties at the formulation and development stages. These pharmaceuticals demonstrate less solubility and bioavailability. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. According to the Classification of Biopharmaceutics, Class II and IV drugs (APIs) exhibit poor solubility, lower bioavailability, and less dissolution. Various technologies are discussed in this article to improve the solubility of poorly water-soluble drugs, for example, the complexation of active molecules, the utilization of emulsion formation, micelles, microemulsions, cosolvents, polymeric micelle preparation, particle size reduction technologies, pharmaceutical salts, prodrugs, the solid-state alternation technique, soft gel technology, drug nanocrystals, solid dispersion methods, crystal engineering techniques and nanomorph technology. This review mainly describes several other advanced methodologies for solubility and bioavailability enhancement, such as crystal engineering, micronization, solid dispersions, nano sizing, the use of cyclodextrins, solid lipid nanoparticles, colloidal drug delivery systems and drug conjugates, referring to a number of appropriate research reports.

4.
J Hazard Mater ; 438: 129538, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35999742

ABSTRACT

Bacterial contaminated water causes potential health issues. Conventional chlorine treatment has shortcomings of environmental hazards and chlorine adoptability by the bacterial cells. Ultrafiltration membrane can intercept bacterial species from feed water. Membrane having anti-biofouling/antifouling properties is needed for the removal of bacteria from feed water. Herein, interpolymer membranes with inherent antimicrobial activity and fouling release property have been prepared by the blend of poly(vinylidene fluoride) (PVDF), poly(vinyl pyrrolidone) and partially long chain alkylated (C12 chain) poly(vinyl imidazole) copolymer (PVIm-co-PVIm-C12) followed by cross-linking of the remaining VIm groups with an activated di-halide compound. The membranes obtain with copolymers of degree of alkyl substitution (DSC12) in the range of 0.75-0.85 and amount in the range of 0.9-3.5% w/w in the casting solutions exhibit good antimicrobial activity (>99 % of inhibition) and dynamic anti-biofouling property. The membrane prepared with 0.9% w/w of the copolymer (DSC12=0.85) shows higher flux recovery ratio (91 % for bacterial filtration and 88 % for protein filtration) compare to a pristine membrane (57 % for bacterial filtration and 58 % for protein filtration). The membrane is able to reject the bacteria completely. Use of small amount of copolymer and facile fabrication of stable anti-biofouling/antifouling membranes show potential for the purification of bacterial contaminated water.


Subject(s)
Anti-Infective Agents , Biofouling , Bacteria , Biofouling/prevention & control , Chlorine , Fluorocarbon Polymers , Imidazoles/pharmacology , Membranes, Artificial , Polymers , Polyvinyl Chloride , Polyvinyls , Ultrafiltration , Water
5.
Science ; 375(6581): 671-677, 2022 02 11.
Article in English | MEDLINE | ID: mdl-35143297

ABSTRACT

The extension of life span driven by 40% caloric restriction (CR) in rodents causes trade-offs in growth, reproduction, and immune defense that make it difficult to identify therapeutically relevant CR-mimetic targets. We report that about 14% CR for 2 years in healthy humans improved thymopoiesis and was correlated with mobilization of intrathymic ectopic lipid. CR-induced transcriptional reprogramming in adipose tissue implicated pathways regulating mitochondrial bioenergetics, anti-inflammatory responses, and longevity. Expression of the gene Pla2g7 encoding platelet activating factor acetyl hydrolase (PLA2G7) is inhibited in humans undergoing CR. Deletion of Pla2g7 in mice showed decreased thymic lipoatrophy, protection against age-related inflammation, lowered NLRP3 inflammasome activation, and improved metabolic health. Therefore, the reduction of PLA2G7 may mediate the immunometabolic effects of CR and could potentially be harnessed to lower inflammation and extend the health span.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/genetics , Adipose Tissue/metabolism , Caloric Restriction , Immune System/physiology , Inflammation , Thymus Gland/immunology , 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism , Adult , Aging , Animals , Down-Regulation , Energy Metabolism , Female , Humans , Inflammasomes/metabolism , Longevity , Lymphopoiesis , Macrophages/immunology , Macrophages/metabolism , Male , Mice , Middle Aged , Mitochondria/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Thermogenesis , Thymus Gland/anatomy & histology , Transcriptome
6.
J Synchrotron Radiat ; 28(Pt 2): 480-489, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33650560

ABSTRACT

The germanium auto-diffusion effects on the inter-atomic distance between the nearest neighbors of the Ga atom in GaP epilayers are investigated using high-resolution X-ray diffraction (HRXRD) and X-ray absorption spectroscopy. The GaP layers grown on Ge (111) are structurally coherent and relaxed but they show the presence of residual strain which is attributed to the auto-diffusion of Ge from the results of secondary ion mass spectrometry and electrochemical capacitance voltage measurements. Subsequently, the inter-atomic distances between the nearest neighbors of Ga atom in GaP are determined from X-ray absorption fine-structure spectra performed at the Ga K-edge. The estimated local bond lengths of Ga with its first and second nearest neighbors show asymmetric variation for the in-plane and out-of-plane direction of GaP/Ge(111). The magnitude and direction of in-plane and out-of-plane microscopic residual strain present in the GaP/Ge are calculated from the difference in bond lengths which explains the presence of macroscopic residual tensile strain estimated from HRXRD. Modified nearest neighbor configurations of Ga in the auto-diffused GaP epilayer are proposed for new possibilities within the GaP/Ge hetero-structure, such as the conversion from indirect to direct band structures and engineering the tensile strain quantum dot structures on (111) surfaces.

7.
Saudi J Gastroenterol ; 27(1): 54-59, 2021.
Article in English | MEDLINE | ID: mdl-32801256

ABSTRACT

BACKGROUND: The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer. METHODS: The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters. RESULTS: We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) (P = 0.017) and immunohistochemistry analysis (P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls (P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage (P = 0.001), histological differentiation (P = 0.001), and tumors with nodal metastasis (P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients. CONCLUSION: In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer.


Subject(s)
Gallbladder Neoplasms , Receptors, Aryl Hydrocarbon , Basic Helix-Loop-Helix Transcription Factors/genetics , Gallbladder Neoplasms/genetics , Humans , RNA, Messenger , Receptors, Aryl Hydrocarbon/genetics , Repressor Proteins/genetics
8.
Soft Matter ; 16(3): 798-809, 2020 Jan 22.
Article in English | MEDLINE | ID: mdl-31834342

ABSTRACT

Achieving controlled membrane permeability using pH-responsive block copolymers is crucial for selective intercellular uptake. We have shown that the pH at the triblock-copolymer micelle interface as compared to its bulk pH can help regulate membrane permeability. The pH-dependent acid/base equilibriums of two different interface-interacting pH probes were determined in order to measure the interfacial pH for a pH-responsive triblock copolymer (TBP) micelle under a wide range of bulk pH (4.5-9.0). According to 1H NMR studies, both pH probes provided interfacial pH at a similar interfacial depth. We revealed that the protonation of the amine moiety at the micelle interface and the subsequent formation of a positive charge caused the interface to become relatively less acidic than that of the bulk as well as an increase in the bulk-to-interfacial pH deviation (ΔpH) from ∼0.9 to 1.9 with bulk pH reducing from 8.0 to 4.5. From the ΔpH vs. interface and bulk pH plots, the apparent and intrinsic protonations or positive charge formation pKa values for the micelle were estimated to be ∼7.3 and 6.0, respectively. When the TBP micelle interacted with an anionic large unilamellar vesicle (LUV) of a binary lipid (neutral and anionic) system at the bulk pH of 7.0, fluorescence leakage studies revealed that the pH increase at the micelle interface from that of the LUV interface (pH ∼ 5.5) made the micelle interface partially protonated/cationic, thereby exhibiting transient membrane permeability. Although the increasing interface protonation causes the interface to become relatively less acidic than the bulk at any bulk pH below 6.5, the pH increase at the micelle interface may not be sufficiently large to maintain the threshold for the amine-protonated condition for effecting transient leakage and therefore, a continuous leakage was observed due to the slow disruption of the lipid bilayer.

9.
Indian J Surg Oncol ; 10(1): 65-71, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30948875

ABSTRACT

Postoperative pancreatic fistula (POPF) is the most feared complication after pancreaticoduodenectomy (PD) that leads to intra-abdominal abscess, sepsis, or bleeding and remains the single most important source of morbidity and mortality after PD. To minimize this dreaded complication, various surgical techniques and modifications of pancreaticoenteric reconstruction have been proposed. However, still POPF does occur even in experienced hands. We herein describe the outcome of 150 post PD patients who underwent duct-to-mucosa (DM) pancreaticojejunostomy (PJ) using a special technique, Blumgart's "through & through" U transpancreatic sutures. The technique is described in detail. Postoperative octreotide and metoclopramide were used in all patients for 3 days. An enhanced recovery (ERAS) protocol was followed in a subset of patients. All patients were ASA grade 1 and had adenocarcinoma of the periampullary region/pancreatic head and underwent standard pylorus resecting PD after due optimization. Eighty-eight (58.7%) patients had pancreatic duct < 3 mm and pancreatic texture was soft to very soft in 112 (74.6%) patients. There was only one International Study Group of Pancreatic Surgery (ISGPS) grade C POPF with concomitant hemorrhage. Five patients developed ISGPS grade B and two grade C, delayed gastric emptying (DGE). There was no 30-day mortality. The average length of hospital stay was 7.3 ± 4.2 days with a median of 6 days in the ERAS subset of patients. Blumgart's "through & through" DMPJ technique is very helpful in reducing the POPF and other complications even in high-risk pancreas (i.e., soft with a small pancreatic duct) and is easy to learn and perform.

10.
Indian J Gastroenterol ; 37(1): 44-49, 2018 01.
Article in English | MEDLINE | ID: mdl-29399748

ABSTRACT

BACKGROUND: Hepatitis E is caused by infection with hepatitis E virus (HEV), which has four well-known genotypes. Genotypes 1 and 2 HEV have been reported from human cases in areas where the disease is highly endemic. By contrast, genotypes 3 and 4 HEV, which primarily infect several animal species worldwide, have been reported mainly from sporadic human cases in non-endemic areas such as Japan and high-income countries of Europe and North America. To determine whether genotype 3/4 HEV cause sporadic disease in India, a disease-endemic area, we determined HEV genotype in a group of patients with such disease. METHODS: A part of the HEV open reading frame (ORF) 1 was amplified and sequenced from sera of 74 patients with sporadic acute viral hepatitis E from four cities in India. The sequences were compared with prototype sequences for various HEV genotypes and subgenotypes and analyzed using phylogenetic tools to determine the genotype of the isolates. For 12 specimens, a part of HEV ORF2 was also similarly analyzed. RESULTS: Partial ORF1 sequences of all the 74 isolates belonged to genotype 1 HEV, with 88.2% to 100% nucleotide identity with the prototype genotype 1 isolates. Partial ORF2 sequences for all the 12 isolates also belonged to genotype 1 HEV. On phylogenetic analysis, 71 isolates clustered with prototype genotype 1a HEV; the remaining three isolates were located between subgenotypes 1a and 1c but were closer to the former. CONCLUSION: Human sporadic acute hepatitis E in India is caused almost exclusively by genotype 1 HEV.


Subject(s)
Genotype , Hepatitis E virus/genetics , Hepatitis E/epidemiology , Hepatitis E/virology , Acute Disease , Hepatitis E/genetics , Hepatitis E virus/isolation & purification , Humans , India/epidemiology , Open Reading Frames/genetics , Viral Proteins/genetics
11.
Sci Rep ; 7(1): 4905, 2017 07 07.
Article in English | MEDLINE | ID: mdl-28687735

ABSTRACT

Effect of charge carrier confinement and ultra-low disorder acquainted in AlGaAs/GaAs multi-quantum well system is investigated via Magneto-photoluminescence spectroscopy. Significant increase of effective mass is observed for the confined exciton in narrow QWs. The foremost reason behind such an observation is due to the induced non-parabolicity in bands. Moreover, as the thickness of the QW are reduced, confined excitons in QW experience atomic irregularities at the hetero-junctions and their effects are prominent in the photoluminescence linewidth. Amount of photoluminescence line-broadening caused by the atomic irregularities at the hetero-junctions is correlated with average fluctuation (δ 1) in QW thickness. The estimated δ 1 for Al0.3Ga0.7As/GaAs QWs are found to be ±(0.14 - 1.6)× 'one monolayer thickness of GaAs layer'. Further, the strong perturbations due to magnetic field in a system helps in realizing optical properties of exciton in QWs, where magnetic field is used as a probe to detect ultralow defects in the QW. Additionally, the influence of magnetic field on the free and bound exciton luminescence is explained by a simple model. The proposed approach for measuring the interface and volume defects in an ultra-low disordered system by Magneto-PL spectroscopy technique will be highly beneficial in high mobility devices for advanced applications.

12.
Indian J Surg Oncol ; 8(3): 348-356, 2017 Sep.
Article in English | MEDLINE | ID: mdl-36118392

ABSTRACT

Periampullary carcinomas are a group of rare lesions around the ampulla of Vater including distal bile duct and duodenum and are very different from pancreatic ductal adenocarcinoma clinically and pathologically, but the molecular alterations in these tumours are less known. Genetic alterations of the KRAS oncogenes, tumour suppressor genes p53, p16 and MADH4 (SMAD4/DPC4) and genome maintenance genes (MLHI, MSH2) are commonly altered in pancreatic adenocarcinoma and have also been described in periampullary cancers, although at lower frequencies. To understand the molecular characteristics of non-pancreatic periampullary carcinomas, ampullary cancers can now be further defined accurately into their intestinal and pancreatobiliary subtypes using histomolecular profiling. KRAS mutation, which occurs in most pancreatic cancers, is found to occur less frequently in ampullary (42-52%), biliary (22-23%) and duodenal cancers (32-35%). Mutations are also found in tumour suppressor genes (p53) and are associated with transformation of adenomas and low-grade carcinomas into high-grade carcinomas. Loss of DPC4 occurs late in ampullary carcinogenesis. This study summarizes the current knowledge in molecular aberrations in non-pancreatic periampullary cancers.

13.
ACS Appl Mater Interfaces ; 9(3): 3102-3112, 2017 Jan 25.
Article in English | MEDLINE | ID: mdl-28009504

ABSTRACT

Simultaneous immobilization and cross-linking of antifouling/low toxic polymers, e.g., poly(ethylenimine) (PEI), dextran (Dex), agarose (Agr), poly(ethylene glycol) (PEG), PEI-Dex, and PEI-PEG conjugates, and stimuli-responsive copolymers on a porous membrane surface in mild reaction conditions is desirable for the enhancement of hydrophilicity, antifouling character, cytocompatibility, and inducing stimuli-responsive behavior. Grafting to technique is required since the precursors of most of these macromolecules are not amenable to surface-initiated polymerization. In this work, we report a versatile process for the simultaneous immobilization and cross-linking of a library of macromolecules on and into the blend membrane (PVDF-blend) of poly(vinylidene fluoride) and poly(methyl methacrylate)-co-poly(chloromethylstyrene). Sequential nucleophilic substitution reaction between activated halide moieties of the copolymer and amine groups of different macromolecules readily provided series of modified membranes. These membranes exhibited antifouling property superior to that of the unmodified membrane. The effectiveness of this technique has been demonstrated by the immobilization of pH or both pH- and temperature-responsive copolymer on PVDF-blend membrane for responsive separation of poly(ethylene oxide) and bovine serum albumin. Silver nanoparticles were also anchored on the select modified membranes surfaces for the enhancement of antibiofouling property. Our approach is useful to obtain verities of functional membranes and selection of membrane for a particular application.

14.
Med Oncol ; 33(5): 40, 2016 May.
Article in English | MEDLINE | ID: mdl-27034264

ABSTRACT

Cell cycle regulators cyclin D1 and cyclin E2 function in G1/S transition by activating downstream cyclin-dependent kinases. Deregulated expression of these cyclins has been reported in various cancers. However, little is known about their clinical significance in gastric carcinoma. We aimed to explore that whether there is differential expression of these cyclins in clinically distinct gastric cancer patients. In this study we recruited a total of 92 subjects including 20 controls and 72 cases of histopathologically proven gastric carcinoma. Expression profiling at transcript level was done by semiquantitative RT-PCR and of protein by immunohistochemistry. Receiver operator characteristics analysis was done for determining diagnostic utility of cyclin D1 and cyclin E2. We demonstrate that cyclins D1 and E2 are frequently overexpressed in early stages of gastric carcinoma. Interestingly, expression of cyclins D1 and E2 significantly correlates with different clinical parameters such as gender, histological type (intestinal and diffuse), tumor location (proximal, middle, and distal), tumor differentiation (differentiated and undifferentiated), tumor invasion (serosal, lymphatic, and venous) and tumor metastasis (lymph node, peritoneal, ascites, and liver). Cyclin D1 has significantly higher sensitivity and specificity as diagnostic biomarker than cyclin E2. Our results suggest that overexpression of cyclin D1 and cyclin E2 is an early event in gastric carcinogenesis. The differential expression of these cyclins may be useful as diagnostic biomarkers for early detection of gastric carcinoma.


Subject(s)
Cyclin D1/metabolism , Cyclins/metabolism , Stomach Neoplasms/metabolism , Biomarkers, Tumor/metabolism , Case-Control Studies , Cyclin D1/genetics , Cyclins/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , ROC Curve , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology
16.
Osteoporos Int ; 27(7): 2373-2378, 2016 07.
Article in English | MEDLINE | ID: mdl-26902093

ABSTRACT

UNLABELLED: To investigate the role of Sirtuin1 in osteoporosis, Sirtuin1 was determined at the femoral neck in female patients undergoing hip operation for fractured hip or osteoarthritis. Reduced Sirtuin1 was found in osteoporotic patients. Pharmacologic activation of Sirtuin1 reduced sclerostin, an inhibitor of bone formation. Activation of Sirtuin1 may be a new direction to generate therapies for osteoporosis. INTRODUCTION: The aim of the study are to investigate the role of Sirtuin1 (Sirt1), an anti-aging factor and a player in age-associated diseases, in osteoporotic hip fractures, and test the hypothesis that Sirt1 is a negative regulator of sclerostin, a bone formation inhibitor, in human femoral bone marrow mesenchymal cells (BM-MSCs). METHODS: Sirt1 and sclerostin were determined by western blot in bone samples obtained intra-operatively from the inferior medial cortex of the femoral neck (calcar region) in female patients undergoing partial hip replacement for fractured neck of femur (N = 10) or hip replacement for osteoarthritis (N = 8) (mean ± SD age 81 ± 8.1 vs. 68 ± 9.3 years; BMI 26.2 ± 3.6 vs. 25.9 ± 7.1 kg/m(2) in osteoporotic and osteoarthritis patients). Calcar thickness and femoral bone mineral density (BMD) were determined preoperatively by X-ray using a digital TraumaCad(™) software and DEXA. Femoral BM-MSCs were collected intra-operatively and treated with SRT3025, a Sirt1 activator. Sclerostin and dentin matrix acidic phosphoprotein (DMP1) were determined by western blot and messenger RNA (mRNA) expression of Lef1 and DMP1 was evaluated by quantitative real-time PCR. RESULTS: Osteoporotic (OP) patients had reduced cortical thickness, femoral neck, and total hip BMD compared to osteoarthritis (OA) patients. Calcar Sirt1 expression was significantly reduced, while sclerostin was markedly increased in OP compared to OA patients. Sirt1 and sclersotin expressions were inversely correlated (r = -0.49, P = 0.047). SRT3025 administration down-regulated sclerostin and up-regulated DMP1 protein level and increased LEF1 and DMP1 mRNA expressions in OP patient-derived BM-MSCs. CONCLUSIONS: Reduced femoral neck Sirt1 may play a role in osteoporotic hip fractures in part via influencing local sclerostin expression. The therapeutic potential of Sirt1 activation in osteoporosis warrants further investigation.


Subject(s)
Femur Neck/metabolism , Hip Fractures/metabolism , Osteoporotic Fractures/metabolism , Sirtuin 1/metabolism , Adaptor Proteins, Signal Transducing , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip , Bone Density , Bone Morphogenetic Proteins/metabolism , Extracellular Matrix Proteins/metabolism , Female , Genetic Markers , Humans , Lymphoid Enhancer-Binding Factor 1/metabolism , Osteoarthritis/surgery , Osteoporosis/surgery , Phosphoproteins/metabolism
17.
J Synchrotron Radiat ; 23(1): 238-43, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26698069

ABSTRACT

Williamson-Hall (WH) analysis is a well established method for studying the microstructural properties of epilayers grown on foreign substrates. However, the method becomes inapplicable in specific cases where the structure factor considerations and the presence of anti-phase domains forbid the data acquisition for certain reflections in conventional high-resolution X-ray diffraction (HRXRD) measurements. Here, this limitation is overcome by exploiting the large intensity (25 µW mm(-2)) and high photon energy (15.5 keV) of the X-ray beam obtained from a synchrotron radiation source. The lateral coherence length, vertical coherence length, tilt and micro-strain of GaAs epilayers grown on Si substrate have been successfully measured using the conventional WH analysis. The microstructure information obtained from the conventional WH analysis based on the data acquired at the synchrotron radiation source is in reasonable agreement with the results obtained from atomic force microscope and surface profiler measurements. Such information cannot be obtained on a laboratory-based HRXRD system where modification of the WH method by involving a set of parallel asymmetric crystallographic planes is found to be essential. However, the information obtained from the modified WH method is along a different crystallographic orientation.

19.
Oncogene ; 35(15): 1996-2002, 2016 Apr 14.
Article in English | MEDLINE | ID: mdl-26119930

ABSTRACT

Germline BAP1 mutations predispose to several cancers, in particular malignant mesothelioma. Mesothelioma is an aggressive malignancy generally associated with professional exposure to asbestos. However, to date, we found that none of the mesothelioma patients carrying germline BAP1 mutations were professionally exposed to asbestos. We hypothesized that germline BAP1 mutations might influence the asbestos-induced inflammatory response that is linked to asbestos carcinogenesis, thereby increasing the risk of developing mesothelioma after minimal exposure. Using a BAP1(+/-) mouse model, we found that, compared with their wild-type littermates, BAP1(+/-) mice exposed to low-dose asbestos fibers showed significant alterations of the peritoneal inflammatory response, including significantly higher levels of pro-tumorigenic alternatively polarized M2 macrophages, and lower levels of several chemokines and cytokines. Consistent with these data, BAP1(+/-) mice had a significantly higher incidence of mesothelioma after exposure to very low doses of asbestos, doses that rarely induced mesothelioma in wild-type mice. Our findings suggest that minimal exposure to carcinogenic fibers may significantly increase the risk of malignant mesothelioma in genetically predisposed individuals carrying germline BAP1 mutations, possibly via alterations of the inflammatory response.


Subject(s)
Asbestos, Crocidolite/toxicity , Mesothelioma/etiology , Peritoneal Neoplasms/etiology , Tumor Suppressor Proteins/genetics , Ubiquitin Thiolesterase/genetics , Animals , Asbestos, Crocidolite/administration & dosage , Ascitic Fluid/chemistry , Chemokines/analysis , Cytokines/analysis , Dose-Response Relationship, Drug , Female , Genetic Predisposition to Disease , Germ-Line Mutation , Heterozygote , Leukocytes/pathology , Macrophages, Peritoneal/classification , Macrophages, Peritoneal/physiology , Male , Mesothelioma/genetics , Mice , Mice, Inbred C57BL , Mineral Fibers/toxicity , Peritoneal Neoplasms/genetics , Peritonitis/etiology , Peritonitis/genetics , Random Allocation , Tumor Suppressor Proteins/deficiency , Tumor Suppressor Proteins/physiology , Ubiquitin Thiolesterase/deficiency , Ubiquitin Thiolesterase/physiology
20.
Int J Pharm ; 491(1-2): 277-84, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-26144387

ABSTRACT

Density functional theoretical (DFT) calculations of the pesticides; 2-chlorophenol (2-CP), 2,4,6-trichlorophenol (TCP) and pentachlorophenol (PCP) have been carried out using 6-311++G** basis set available on Gaussian-09 software in order to optimize the molecular structures. The optimized geometry of the molecules has been found to possess Cs symmetry. The charge transfer phenomena occurring in the molecules have been exhibited by (HOMO-LUMO) analysis. The molecular ESP values and mappings of electron density iso-surface with the molecular electrostatic potential (MEP), have been carried out to achieve the information of the size, shape, charge density distribution and site of chemical reactivity of the molecules. Thermo molecular characteristics have been computed to achieve essential environmental influence on the activities of fungicides.


Subject(s)
Chlorophenols/chemistry , Fungicides, Industrial/chemistry , Electron Spin Resonance Spectroscopy , Electrons , Models, Molecular , Quantum Theory , Software , Spectrum Analysis, Raman
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