Search

Chronic hepatitis caused by the hepatitis C virus (HCV) is closely linked with the advancement of liver disease. The research hypothesis suggests that the NS5B enzyme (non-structural 5B protein) of HCV plays a pivotal role in facilitating viral replication within host cells. Hence, the objective of the present investigation is to identify the binding interactions between the structurally diverse phytotherapeutics and those of the catalytic residue of the target NS5B polymerase protein. Results of our docking simulations reveal that compounds such as arjunolic acid, sesamin, arjungenin, astragalin, piperic acid, piperidine, piperine, acalyphin, adhatodine, amyrin, anisotine, apigenin, cuminaldehyde, and curcumin exhibit a maximum of three interactions with the catalytic residues (Asp 220, Asp 318, and Asp 319) present on the Hepatitis C virus NS5B polymerase of HCV. Molecular dynamic simulation, particularly focusing on the best binding lead compound, arjunolic acid (−8.78 kcal/mol), was further extensively analyzed using RMSD, RMSF, Rg, and SASA techniques. The results of the MD simulation confirm that the NS5B-arjunolic acid complex becomes increasingly stable from 20 to 100 ns. The orientation of both arjunolic acid and sofosbuvir triphosphate (standard) within the active site was investigated through DCCM, PCA, and FEL analysis, indicating highly stable interactions of the lead arjunolic acid with the catalytic region of the NS5B enzyme. The findings of our current investigation suggest that bioactive therapeutics like arjunolic acid could serve as promising candidates for limiting the NS5B polymerase activity of the hepatitis C virus, offering hope for the future of HCV treatment. [ABSTRACT FROM AUTHOR]

In recent years, vector-to-vector mapping-based raw waveform biosignal enhancement methods have gained significant attention in remote health monitoring system. In this paper, a novel end-to-end convolutional encoder–decoder (CED) model with stacked gated recurrent unit (SGRU) is proposed to learn sequential information of biosignal for signal enhancement. The proposed model CED-SGRU employs convolutional neural network to capture the spatial features and SGRU to capture temporal distributions of the biosignal layer by layer which increases the robustness of the proposed model. This work applies mean absolute error as a loss function for CED-SGRU-based vector-to-vector model. The proposed method has been evaluated on three foremost required biosignals, namely electrocardiogram, photoplethysmography and heart rate signals for diagnosing cardiovascular diseases. Experimental result shows outstanding denoising capability of the proposed CED-SGRU model on three biosignals which yields significantly higher reconstruction signal-to-noise ratio value and lower average absolute error, root mean square error and percent root mean square difference values when compared with state-of-the-art-methods. Moreover, the simple architecture of SGRU lowers the complexity of the model; thereby, reducing the inference time for denoising and restoring compressed biosignal tasks is fairly compared with baseline models, namely recurrent neural network model and long short-term memory model. [ABSTRACT FROM AUTHOR]

The pervasive presence of microplastics within river ecosystems has a profound and often underestimated detrimental impact. These minuscule yet persistent particles have infiltrated diverse biological habitats, making their detrimental effects on aquatic life increasingly concerning worldwide. The ability of microplastics to accumulate within aquatic organisms further exacerbates this concern. Consequently, the monitoring of microplastic pollution in surface water environments has emerged as a crucial endeavour, offering invaluable insights into the extent of this ecological threat. This study delved into the contamination levels of microplastics within two bivalve species, Perna viridis and Villorita cyprinoides, along the Chandragiri River in Kerala and Karnataka, South-West India, spanning eight distinct locations. The investigation yielded a significant discovery, with a total of 667 microplastic particles extracted from 288 individuals. On average, each individual bivalve harboured approximately 2.31 ± 0.93 microplastic items. Notably, these microplastic particles exhibited a wide range of morphological characteristics, underscoring their diverse origins and pathways into the ecosystem. Furthermore, five polymer types of microplastics were unequivocally confirmed through FTIR-ATR analysis, shedding light on the types of plastics that pose a threat to the riverine ecosystem. The findings of this study contribute to a growing body of evidence highlighting the global threat of microplastic pollution, urging international collaboration and innovative solutions to prevent further contamination and remediate existing microplastic burdens in aquatic environments. Highlights: • Microplastic contamination is a major concern in river ecosystems. • Microplastic in two bivalve species were characterized at Chandragiri River India. • The microplastics had diverse shapes and were composed of five different polymers. • This study emphasizes the need to tackle river microplastic pollution. [ABSTRACT FROM AUTHOR]

The use of Internet of Things (IoT) that integrate smart bio sensor devices to the internet and shows individual health in real time. Healthcare organizations gain measurable insights into their most demanding problems like chronic diseases which demands long term monitoring. Various types of nano-sensors like Ingestible embedded in pills, Blood sampling sensor and tissue sensors are used in Healthcare IoT. Such implantable device collects, process and sends the vital signs called biosignals from particular organ of the human body where it has been implanted or fixed throughout the day to remote clinician. Such prolonged monitoring may weaken the battery power of nano-sensors. Since nano-sensors are miniaturized in nature and completely relies on its battery, energy awareness is incorporated in this paradigm that can help to avoid unnecessary energy consumption. This is achieved by data compression scheme. As the nano-sensors are light weight devices the designed algorithm should be low complex as well as efficient. As well, the signal acquired through this wireless sensor device are prone to be contaminated with noises because of the wearer's movements. In this study, regularized denoising autoencoder (DAE) has been employed to compress and recover the signal from its noisy version. Lasso (Least Absolute Shrinkage and Selection Operator) and Ridge regularization concepts are used and contrasted in this article. The cost function now includes these penalty clauses to address the overfitting problem. The experimental findings demonstrate that LASSO Norm has outperformed over RIDGE in 18% for ECG, 57% for EMG & 31% for EEG signal with respect to Quality Score. The datasets used in this investigation were taken from a database that was open to the public for testing. [ABSTRACT FROM AUTHOR]

Introduction: Small fiber neuropathy [SFN] is a common peripheral neurologic disorder with a vast array of implicated etiologies. It has previously been proposed that some forms of immune-mediated small fiber neuropathy are driven by vasculitis, though antinuclear cytoplasmic antibodies [ANCA] antibodies have not commonly been reported in association with SFN, thus far. We present this case series to discuss the observation of a possible novel association between ANCA and SFN. Methods: This is a retrospective case series of 6 patients with SFN and ANCA positivity, with and without systemic manifestations. Patients included were diagnosed with SFN by skin biopsy or autonomic function testing and were seropositive for ANCA by ELISA. Results: Six patients are outlined, including 4 females and 2 males. Antigen specific antibodies were MPO alone in 4 cases, PR3 alone in 1 case and both MPO and PR3 in 1 case. Systemic vasculitis was noted in 2 patients. Five patients received immunosuppression. Three patients experienced partial improvement, while symptoms stabilized in 3 patients. Discussion: This is the first series of patients with suspected immune-mediated SFN and ANCA antibody positivity, raising the possibility of ANCA mediated isolated SFN. This is in contradistinction to the more typical ANCA-mediated peripheral neuropathy manifestations of mononeuropathy multiplex or axonal sensorimotor neuropathy. We cannot unequivocally prove ANCA-associated vasculitis [AAV] causality in these cases; however, the stabilization in SFN symptomatology and associated improvement in ANCA antibody titer, after AAV treatment, may be indicative of an association. [ABSTRACT FROM AUTHOR]

Background: Keratoconus is a corneal ectatic disease caused by stromal thinning leading to astigmatism and progressive loss of vision. Loss of the keratocytes and excessive degradation of collagen fibres by matrix metalloproteinases are the molecular signatures of the disease. Despite several limitations, corneal collagen cross-linking and keratoplasty are the most widely used treatment options for keratoconus. In the pursuit of alternative treatment modalities, clinician scientists have explored cell therapy paradigms for treating the condition. Methods: Articles pertaining to keratoconus cell therapy with relevant key words were used to search in PubMed, Researchgate, and Google Scholar. The articles were selected based on their relevance, reliability, publication year, published journal, and accessibility. Results: Various cellular abnormalities have been reported in keratoconus. Diverse cell types such as mesenchymal stromal cells, dental pulp cells, bone marrow stem cells, haematopoietic stem cells, adipose-derived stem cells apart from embryonic and induced pluripotent stem cells can be used for keratoconus cell therapy. The results obtained show that there is a potential for these cells from various sources as a viable treatment option. Conclusion: There is a need for consensus with respect to the source of cells, mode of delivery, stage of disease, and duration of follow-up, to establish a standard operating protocol. This would eventually widen the cell therapy options for corneal ectatic diseases beyond keratoconus. [ABSTRACT FROM AUTHOR]

Left ventricular adaptations can be a complex process under the influence of aortic stenosis (AS) and comorbidities. This study proposed and assessed the feasibility of using a motion-corrected personalized 3D + time LV modeling technique to evaluate the adaptive and maladaptive LV response to aid treatment decision-making. A total of 22 AS patients were analyzed and compared against 10 healthy subjects. The 3D + time analysis showed a highly distinct and personalized pattern of remodeling in individual AS patients which is associated with comorbidities and fibrosis. Patients with AS alone showed better wall thickening and synchrony than those comorbid with hypertension. Ischemic heart disease in AS caused impaired wall thickening and synchrony and systolic function. Apart from showing significant correlations to echocardiography and clinical MRI measurements (r: 0.70–0.95; p < 0.01), the proposed technique helped in detecting subclinical and subtle LV dysfunction, providing a better approach to evaluate AS patients for specific treatment, surgical planning, and follow-up recovery. [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin A nephropathy (IgAN) is a progressive inflammatory kidney disease requiring long-term treatment to reduce the risk of progression to kidney failure. Here, we present two systematic literature reviews (SLRs) to identify and summarize literature reporting the humanistic and economic burden of IgAN. Methods: Electronic literature databases (Ovid Embase, PubMed, and Cochrane) were searched for relevant literature on 29 November 2021, supplemented with gray literature searches. Studies reporting any health-related quality of life (HRQoL) or health state utility outcomes in IgAN patients were included in the humanistic impact SLR, and studies reporting the costs and healthcare resource utilization associated with or economic models of IgAN disease management were included in the economic burden SLR. Narrative synthesis was used to discuss the heterogeneous studies included in the SLRs. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Cochrane guidelines were followed, and all included studies were assessed for risk of bias using the Center for Evidence-Based Management tool for Critical Appraisal of a Survey or the Drummond Checklist. Results: A total of 876 and 1122 references were identified from electronic and gray literature searches for humanistic and economic burden, respectively. Three studies reporting humanistic impact and five studies reporting economic burden met criteria for inclusion in these SLRs. The included humanistic studies reported patient preferences in the USA and China, HRQoL for patients with IgAN in Poland, and impact of exercise on HRQoL for patients with IgAN in China. The five economic studies reported costs of IgAN treatment in Canada, Italy, and China, along with two economic models from Japan. Discussion: Current literature suggests IgAN is associated with substantial humanistic and economic burdens. However, these SLRs demonstrate the paucity of research conducted to specifically describe the humanistic or economic burden of IgAN and highlight the need for further research. [ABSTRACT FROM AUTHOR]

Waste recycling and up-cycling strategies are important for the sustainability of resources on earth, as water is the key to the sustenance of life. In the present study, oxidant-modified biochar (OBC) is used for the adsorptive removal of basic fuchsin from aqueous systems. Characterization of the adsorbent was done using various analytical techniques. Morphological analysis shows that OBC was irregular in shape with a spongier structure. The adsorbent is thermally stable until 850 °C. Functional groups on OBC before and after adsorption were determined using Raman spectroscopy and FTIR. Through batch investigations, the effect of different experimental factors on the adsorption process, such as pH, biosorbent dosage, and initial concentration of pollutant, were optimized. The highest removal efficiency of 98.28% was seen at pH 6.0 with 0.05 g adsorbent dosage at the initial pollutant concentration of 10 mg/L. Freundlich isotherm and pseudo-second-order kinetics model fits to the adsorption process. The toxicity of basic fuchsin before and after adsorption was compared by exposing Vigna radiata seeds to the dye. The growth inhibition reduced to 26.86% from 67.67% after the adsorption process. Thus, oxidant-modified Biochar was effective in the adsorptive removal of basic fuchsin from water. [ABSTRACT FROM AUTHOR]

Purpose: Few studies examine whether maternal and neonatal outcomes differ by time from metabolic and bariatric surgery (MBS) to conception. We describe maternal and neonatal outcomes among women with pregnancy after Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) overall and by whether conception occurred during the period when pregnancy is not recommended (< 18 months postoperative) versus later. Materials and Methods: A prospective cohort study enrolled 135 US adult women (median age, 30 years, body mass index [BMI], 47.2 kg/m2) who underwent RYGB or SG (2006–2009) and subsequently reported ≥ 1 pregnancy within 7 years. Participants self-reported pregnancy-related information annually. Differences in prevalence of maternal and neonatal outcomes by postoperative conception timeframe (< 18 versus ≥ 18 months) were assessed. Results: Thirty-one women reported ≥ 2 postoperative pregnancies. At time of postoperative conception (median 26 [IQR:22–52] months postoperative) median BMI was 31 (IQR:27–36) kg/m2. Excessive gestational weight gain (55%), cesarean section (42%) and preterm labor or rupture of membranes (40%) were the most common maternal outcomes. Forty percent of neonates had a composite outcome of still birth (1%), preterm birth (26%), small for gestational age (11%), or neonatal intensive care unit admission (8%). Prevalence of outcomes did not statistically significantly differ by timeframe. Conclusion: In US women who conceived ≤ 7 years following RYGB or SG, 40% of neonates had the composite neonatal outcome. The prevalence of maternal and neonatal outcomes post-MBS were not statistically significant by conception timeframe. [ABSTRACT FROM AUTHOR]

In the present study, the 3-1H-benzo [d] imidazole-2-yl-quinolin-2-ol (BIMQ) was used as a corrosion inhibitor and its mitigation performance against the corrosion of mild steel (MS) in 1 M HCl and H2SO4 solution was examined through gravimetric weight loss, potentiodynamic polarization (PDP), and electrochemical impedance studies (EIS). The surface morphology was examined using scanning electron microscopy (SEM), and UV–visible (UV–Vis) spectroscopic studies were carried out to study the electron transfer. Theoretical studies have been implemented using quantum chemical calculations and molecular dynamics simulation. Weight loss studies revealed that the corrosion rates decreased with increasing concentration of BIMQ. Polarization results confirmed that the presence of BIMQ suppressed the metal dissolution and hydrogen evolution at the anodic and cathodic regions in both acidic media. The inhibitor showed 86.0 and 94.2% inhibition efficiency at a 50 ppm concentration of BIMQ. EIS results indicated that the BIMQ reduces the speed of corrosion reaction of MS in 1 M HCl and H2SO4. Inhibitor adsorption isotherm data revealed that the inhibition process obeys Langmuir isotherm. The UV–Vis absorption spectrum confirmed the electron transfer, and SEM studies showed that the corrosion of MS surface is significantly reduced in the presence of BIMQ. Quantum chemical calculations revealed that the investigated molecule has a widespread electron density and active sites over the entire molecular structure. Molecular dynamics simulation indicated that the molecule stands parallel to the iron surface in close contact to the iron surface. [ABSTRACT FROM AUTHOR]

In the present study, the 3-1H-benzo [d] imidazole-2-yl-quinolin-2-ol (BIMQ) was used as a corrosion inhibitor and its mitigation performance against the corrosion of mild steel (MS) in 1 M HCl and H2SO4 solution was examined through gravimetric weight loss, potentiodynamic polarization (PDP), and electrochemical impedance studies (EIS). The surface morphology was examined using scanning electron microscopy (SEM), and UV–visible (UV–Vis) spectroscopic studies were carried out to study the electron transfer. Theoretical studies have been implemented using quantum chemical calculations and molecular dynamics simulation. Weight loss studies revealed that the corrosion rates decreased with increasing concentration of BIMQ. Polarization results confirmed that the presence of BIMQ suppressed the metal dissolution and hydrogen evolution at the anodic and cathodic regions in both acidic media. The inhibitor showed 86.0 and 94.2% inhibition efficiency at a 50 ppm concentration of BIMQ. EIS results indicated that the BIMQ reduces the speed of corrosion reaction of MS in 1 M HCl and H2SO4. Inhibitor adsorption isotherm data revealed that the inhibition process obeys Langmuir isotherm. The UV–Vis absorption spectrum confirmed the electron transfer, and SEM studies showed that the corrosion of MS surface is significantly reduced in the presence of BIMQ. Quantum chemical calculations revealed that the investigated molecule has a widespread electron density and active sites over the entire molecular structure. Molecular dynamics simulation indicated that the molecule stands parallel to the iron surface in close contact to the iron surface. [ABSTRACT FROM AUTHOR]

Preeclampsia is a leading cause of maternal and neonatal morbidity and mortality. Chronological age and race are associated with preeclampsia, but the role of these factors is not entirely understood. We hypothesized that DNA methylation age, a measure of biological age, would be higher in individuals with preeclampsia than in individuals with normotensive pregnancy and that DNA methylation age would differ by race across pregnancy. This was a longitudinal, exploratory study of 56 pregnant individuals (n = 28 preeclampsia cases and n = 28 normotensive controls). Genome-wide DNA methylation data were generated from trimester-specific peripheral blood samples. DNA methylation age was estimated using the "Improved Precision" clock, and ∆age, the difference between DNA methylation age and chronological age, was computed. DNA methylation age was compared with chronological age using Pearson correlations. The relationships between ∆age and preeclampsia status, self-reported race, and covariates were tested using multiple linear regression and performed both with and without consideration of cell-type heterogeneity. We observed strong correlation between chronological age and DNA methylation age across pregnancy, with significantly stronger correlation observed in White participants than in Black participants. We observed no association between ∆age and preeclampsia status. However, ∆age was higher in participants with higher pre-pregnancy body mass index in trimester 1 and lower in Black participants than in White participants in trimesters 2 and 3. Observations were largely consistent when controlling for cell-type heterogeneity. Our findings in a small sample support the need for additional studies to investigate the relationship between race and biological age, which could provide further insight into racial disparities across pregnancy. However, this study does not support an association between ∆age and preeclampsia status. [ABSTRACT FROM AUTHOR]

In the present study, two structurally diverse novel glitazones were designed and synthesized for activation of central PGC-1α signaling through stimulation of PPAR-γ receptor. The functional interaction between PGC-1α and PPAR-γ is a key interaction in the normal physiology of neuroprotective mechanism. Therefore, activation of PPAR-γ–dependent PGC-1α co-activator signaling could be an effective strategy to exhibit neuroprotection in several neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, and cerebral ischemia. As part of rational design, analogs were designed manually based on principles of bioisosterism, followed by virtually screened using docking to predict the mode of interaction of compound towards the binding site and molecular dynamic simulation to observe the structural changes that occur during compound interaction with active site. The designed two glitazones (G1, G2) were synthesized and structurally analyzed. As part of evaluation, synthesized glitazones were subjected for preliminary neuroprotective evaluation in Lipopolysaccharide (LPS) intoxicated SH-SY5Y neuroblastoma cells. The results indicate that pre-treatment with synthesized glitazones have increased the percentage cell viability, protected the cell morphology, and decreased the release of pro-inflammatory cytokines (IL-1β, TNF-α), lipid peroxide (LPO), and nitric oxide (NO) level in LPS intoxicated SH-SY5Y cells. Interestingly, among the two glitazones, G2 has shown significant neuroprotection in comparison to G1 and neuroprotective effect exerted by G2 was similar and comparable with the standard pioglitazone. Altogether, neuroprotection exhibited by this non-thiazolidione–based glitazones during neuroinflammatory conditions may be attributed to the activation of central PGC-1α signaling via PPAR-γ receptor. [ABSTRACT FROM AUTHOR]

Exosomes are extracellular microvesicles with a particle size of 30-100 nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the formulation stored at − 80°C was stable for 6 months as determined by particle size analysis, drug load, and antiproliferative activity. The uptake of exosomes by cancer cells involved caveolae/clathrin-mediated endocytosis. Oral administration of exosomal curcumin (ExoCUR) in Sprague-Dawley rats demonstrated 3-5 times higher levels in various organs versus free agent. ExoCUR showed enhanced antiproliferative activity against multiple cancer cell lines including, breast, lung, and cervical cancer compared with the free curcumin. ExoCUR showed significantly higher anti-inflammatory activity measured as NF-κB activation in human lung and breast cancer cells. To determine in vivo antitumor activity, nude mice bearing the cervical CaSki tumor xenograft were treated with ExoCUR by oral gavage, curcumin diet, exosomes alone, and PBS as controls. While curcumin via dietary route failed to elicit any effect, exosomes had a modest (25-30%) tumor growth inhibition. However, ExoCUR showed significant inhibition (61%; p < 0.01) of the cervical tumor xenograft. No gross or systemic toxicity was observed in the rats administered with the exosomes or ExoCUR. These results suggest that exosomes can be developed as potential nano carriers for delivering curcumin which otherwise has encountered significant tissue bioavailability issues in the past. [ABSTRACT FROM AUTHOR]

The purpose of this study was to examine circulating maternal follistatin-like 3 (FSTL-3) by gestational age and obesity in pregnancy and preeclampsia. FSTL-3 was quantified in maternal plasma collected in each trimester from prepregnancy body mass index-determined groups: 15 lean and 24 obese controls and 20 obese women who developed preeclampsia. Repeated measures mixed models and logistic regression were conducted (P ≤ .05). FSTL-3 was not related to maternal adiposity. FSTL-3 changed across pregnancy in lean controls and obese preeclampsia but not in obese controls. FSTL-3 was higher in preeclampsia in the second trimester compared to lean controls and in the third trimester compared to both control groups. Elevated FSTL-3 at mid-gestation was associated with an increased odds of preeclampsia (odds ratio 3.15; 95% confidence interval 1.19-8.36; P = .02). Elevated FSTL-3 concentrations were attributable to preeclampsia and were associated with increased likelihood of later developing preeclampsia, suggesting further study as a biomarker prior to clinically evident disease. [ABSTRACT FROM AUTHOR]

Lymphangiography and thoracic duct embolization are well-described techniques for the diagnosis and treatment of thoracic lymphatic leaks refractory to conservative treatment. However, thoracic duct embolization is not an option in patients with abdominal chylous leaks. The present report describes a 68-year-old man who underwent an aortomesenteric bypass complicated by a high-output postoperative chylothorax (>2,000 ml/day) and chylous ascites (>7,000 ml/paracentesis). Ultrasound-guided intranodal lymphangiography demonstrated a retroperitoneal lymphatic leak tracking along the vascular graft into the peritoneal cavity. Computed tomography-guided lymphatic duct occlusion with N-butyl cyanoacrylate glue was performed, resulting in successful treatment of both chylothorax and chylous ascites. [ABSTRACT FROM AUTHOR]

Summary: The present study shows no adverse effects of the anti-diabetic drug metformin on bone mass and fracture healing in rodents but demonstrates that metformin is not osteogenic in vivo, as previously proposed. Introduction: In view of the increased incidence of fractures in patients with type 2 diabetes mellitus (T2DM), we investigated the effects of metformin, a widely used T2DM therapy, on bone mass and fracture healing in vivo using two different rodent models and modes of metformin administration. Methods: We first subjected 12-week-old female C57BL/6 mice to ovariectomy (OVX). Four weeks after OVX, mice received either saline or metformin administered by gavage (100 mg/kg/daily). After 4 weeks of treatment, bone micro-architecture and cellular activity were determined in tibia by micro-CT and bone histomorphometry. In another experiment, female Wistar rats aged 3 months were given only water or metformin for 8 weeks via the drinking water (2 mg/ml). After 4 weeks of treatment, a mid-diaphyseal osteotomy was performed in the left femur. Rats were sacrificed 4 weeks after osteotomy and bone architecture analysed by micro-CT in the right tibia while fracture healing and callus volume were determined in the left femur by X-ray analysis and micro-CT, respectively. Results: In both models, our results show no significant differences in cortical and trabecular bone architecture in metformin-treated rodents compared to saline. Metformin had no effect on bone resorption but reduced bone formation rate in trabecular bone. Mean X-ray scores assessed on control and metformin fractures showed no significant differences of healing between the groups. Fracture callus volume and mineral content after 4 weeks were similar in both groups. Conclusions: Our results indicate that metformin has no effect on bone mass in vivo or fracture healing in rodents. [ABSTRACT FROM AUTHOR]

In the present investigation, we described herein the molecular properties prediction by Molinspiration () and synthesized a series of 17 2-(substituted benzylidene/ethylidene)- N-(substituted phenyl)hydrazinecarboxamide analogues. All the title compounds ( 4a- q) followed the Lipinski 'Rule of Five.' The synthesized compounds were characterised by elemental analyses and spectral data followed by anticonvulsant activity according to the Antiepileptic Drug Development Programme Protocol. 2-(4-Hydroxybenzylidene)- N-(2-chlorophenyl)hydrazinecarboxamide ( 4j) was found to be the most active compound of the series showing protection at 4.0 h at a dose of 100 mg/kg against maximal electroshock seizure test and 50 % (2/4, 0.25, 1-2 h) and 100 % (4/4, 0.5 h) protection in 6 Hz psychomotor seizure test without showing any neurotoxicity. N-(2-chlorophenyl)hydrazine carboxamide ( 3b) showed 100 % (4/4, 0.25-2 h) and 66.6 % (2/3, 4 h) protection in 6 Hz psychomotor seizure test. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Curcumin, an anti-oxidant, anti-inflammatory, and anti-neoplastic agent, exhibited limited oral efficacy due to its poor bioavailability. To overcome this limitation, polymeric implants for continuous systemic delivery of curcumin were developed and tested for their safety and biocompatibility. Two 2-cm polycaprolactone implants containing polyethylene glycol and 20% ( w/ w) curcumin were grafted subcutaneously at the back of the Augustus Copenhagen Irish rats. Rats were euthanized and blood was analyzed for various hematological parameters; biochemical markers of liver/kidney function and local tissues were analyzed for local inflammatory reactions. Curcumin implants exhibited biphasic release kinetics with ∼3.6 + 0.8, 5.8 ± 1.1, 13.1 ± 2.1, 21.8 ± 0.3, 38.1 ± 0.6, and 47.2 ± 1.6 mg cumulative curcumin being released from both the implants after 1, 4, 12, 25, and 90 days. No significant differences in various hematological parameters (like white blood cells, red blood cells, hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin), liver enzymes (like aspartate transaminase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, amylase, or lipase), or biochemical parameters of kidney function (like blood urea nitrogen, creatinine, Ca, Na, and Cl levels) were observed at any of these time points. However, a significant increase in serum phosphorus levels was observed at all the time points in sham implants as well as in curcumin diet and implant groups. Local implantation site showed foreign body granulomatous reaction with influx of histiocytes and occasional multi-nucleated giant cells with sham implants and was minimal around the curcumin implants. These polymeric implants were found to have little or no systemic toxicity with an acute reaction at local site which was reduced significantly by curcumin implants. [ABSTRACT FROM AUTHOR]

The article discusses a study on the identification of intragenic FOXL2 mutations in Indian families with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). It is a genetic condition characterized by eyelid malformation. The researchers reported a nonsense mutation in a BPES type I family and a recurrent duplication leading to a polyalanine expression in a BPES type II family. It was found that the genotype-phenotype correlations are in agreement with previous mutation studies in BPES.

The blepharophimosis syndrome (BPES) is an autosomal dominant developmental disorder in which craniofacial/eyelid malformations are associated (type I) or not (type II) with premature ovarian failure (POF). Mutations in the FOXL2 gene, encoding a forkhead transcription factor, are responsible for both types of BPES. Heterozygous polyalanine expansions of +10 residues (FOXL2–Ala24) account for 30% of FOXL2 mutations and are fully penetrant for the eyelid phenotype. Here we describe the first homozygous FOXL2 mutation leading to a polyalanine expansion of +5 residues (FOXL2–Ala19). This novel mutation segregates in an Indian family where heterozygous mutation carriers are unaffected whereas homozygous individuals have the typical BPES phenotype, with proven POF in one female. Expression of the FOXL2–Ala19 protein in COS-7 cells revealed a significantly higher cytoplasmic retention compared to the wild-type protein. This is the first study providing genetic evidence for a recessive inheritance of BPES associated with ovarian dysfunction. [ABSTRACT FROM AUTHOR]

Interaction of 12-B heteropolyanions, [XMoO], where X=Ce, Th and U, with tetravalent transition metal ions Mn and V results in the formation of three well defined complexes, viz., (NH)[MnThMoO]·10HO (I), (NH)[MnUMoO]·8HO (II) and (NH)[VCeMoO]·8HO (III), which are characterised by IR, Raman and EPR spectroscopies. Negative shift in the stretching frequency of Mo-O bond in IR spectra and appearance of a strong band at 818 cm in Raman spectra support the formation of these complexes. EPR spectra of complexes (I) and (II) show a predominant signal at g=4 and a weak signal at g=2 (with hyperfine coupling fromMn), characteristic of d system, ( S=3/2 and I=5/2) with large zero field splitting, showing distortion from octahedral symmetry. EPR parameters of the vanadium complex (III) show the d-electron to be more localised on vanadium(IV) supporting the formulation of vanadium not to be a part of the 'Mo' unit. The oxidising property of complexes (I) and (II) is studied using glucose as the substrate. [ABSTRACT FROM AUTHOR]

Bonding and redox properties of mono- and dititanium substituted 12-heteropolytungsto-phosphates and their complexes with bivalent Mn, Co, Ni and Cu are studied by UV-Vis, ESR and cyclicvoltammetric techniques. The heteropoly blue analogue [TiTiWPO] is unstable and its presence in solution is proved by optical and ESR spectroscopy. ESR results reveal that the odd electron is trapped on the titanium atom at 77 K. The optical electronegativity of Ti(III) in this heteropoly blue is estimated to be 2.4 from the intervalence charge transfer (IVCT) bands. X-ray powder diffraction results show that the complexes KM[TiWPO].xHO(M = Cu or Mn) are isomorphous with K[TiWPO].6HO. Electronic spectroscopy indicates very high symmetry around the bivalent metal ion M in the KM[TiWPO].xHO complexes. This high symmetry is confirmed in KCu[TiWPO] by the observation of dynamic Jahn-Teller (JT) distortion at 300 K and static JT distortion at 77 K. [ABSTRACT FROM AUTHOR]

The Ti-substituted heteropolytungstates K7[TiIVW11–BO40] and K6[VVTiIVW10PO40] have been synthesized and characterized by elemental analyses and spectroscopic techniques. Their redox properties have been studied by cyclic voltammetry, and the compounds were found to be more difficult to reduce than the unsubstituted heteropolyanion. The one- and two-electron reduced heteropoly blues of [VVTiIVW10PO40]6−, namely [VIVTiIVW10PO40]7− and [VIVTiIIIW10PO40]8−, have also been prepared by chemical methods. Their optical spectra show low-energy intervalence charge-transfer bands as well as the expected d–d transitions. The optical and e.s.r. investigations indicate that VIV and TiIII are not vicinal in [VIVTiIIIW10PO40]8−. [ABSTRACT FROM AUTHOR]