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Summary: Fabrication of stimuli-responsive superstructure capable of delivering chemotherapeutics directly to the cancer cell by sparing healthy cells is crucial. Herein, we developed redox-responsive hollow spherical assemblies through self-assembly of disulfide-linked cysteine-diphenylalanine (SN). These fluorescent hollow spheres display intrinsic green fluorescence, are proteolytically stable and biocompatible, and allow for real-time monitoring of their intracellular entry. The disulfide bond facilitates selective degradation in the presence of high glutathione (GSH) concentrations, prevalent in cancer cells. We achieved efficient encapsulation (68.72%) of the anticancer drug doxorubicin (Dox) and demonstrated GSH-dependent, redox-responsive drug release within cancerous cells. SN-Dox exhibited a 20-fold lower effective concentration (2.5 μM) for compromising breast cancer cell viability compared to non-malignant cells (50 μM). The ability of SN-Dox to initiate DNA damage signaling and trigger apoptosis was comparable to that of the unencapsulated drug. Our findings highlight the potential of SN for creating site-specific drug delivery vehicles for sustained therapeutic release.

In the present study, we investigated whether treatment with KRG improve the parameters of immune activity such as the cytotoxicity, populations of CD4+ CD8+T cell, CD3−CD172−CD8+ NK cell and CD172+ monocyte as well as natural cytotoxicity receptors such as Nkp46, Nkp44, Nkp30. In results, KRG significantly increased these immune activities. These results indicate that KRG has distinct immune-enhancing effects by increasing the roles of T cells and NK cell in porcine.

Background Context: Both Transforaminal (TF) and Interlaminar (IL) endoscopic approaches are established techniques of decompression for lumbar compressive radiculopathy. In the absence of adequate literature, there is always some dilemma in selecting the approach for endoscopic decompression leading to long learning curves and high chances of inadequate decompression, iatrogenic instability, dural tear, or dysesthesia. Hence authors propose a new surgical nomenclature and algorithm for selection of endoscopic approach. Methods: This retrospective study included 396 of 626 consecutive patients who met the inclusion criteria, who underwent either TF (n=302) or IL (n=202) full endoscopic spine surgery. MRI findings of every patient were classified as per FAPDIS (Facet angle, Anterior pathology, Posterior pathology, Dorsal, Inferior, and Superior migration) algorithm. Inter-observer variations were calculated. The targeted nomenclature was used to define the selection of endoscopic TF or IL approach for symptomatic nerve root decompression. All patients were followed up for preop and postop 6 months VAS and Oswestry Disability Index score for validation of FAPDIS algorithm. Results: Median age: 46.8 years; Sides and levels operated 330 single-level ipsilateral, 54 multiple-level ipsilateral, 6 single-level bilateral, and 6 multiple-level bilateral. Interobserver agreement in the selection of TF approach was 0.873 and IL approach was 0.882. Interobserver variability was also calculated for each FAPDIS factor, selection of P3 and P4 pathology was the main reason for disagreement. All other FAPDIS factors show good to excellent correlation. The overall VAS score decreased from a preoperative value of 9 to 1 at 6 months follow-up (p-value < 0.001), and the overall Oswestry Disability Index score improved from 89 to 12 (p-value

Traditionally, Asian ginseng or Korean ginseng, Panax ginseng has long been used in Korea and China to treat various diseases. The main active components of Panax ginseng is ginsenoside, which is known to have various pharmacological treatment effects such as antioxidant, vascular easing, anti-allergic, anti-inflammatory, anti-diabetes, and anticancer. Most reactive oxygen species (ROS) cause chronic diseases such as myocardial symptoms and cause fatal oxidative damage to cell membrane lipids and proteins. Therefore, many studies that inhibit the production of oxidative stress have been conducted in various fields of physiology, pathophysiology, medicine and health, and disease. Recently, ginseng or ginsenosides have been known to act as antioxidants in vitro and in vivo results, which have a beneficial effect on preventing cardiovascular disease. The current review aims to provide mechanisms and inform precious information on the effects of ginseng and ginsenosides on the prevention of oxidative stress and cardiovascular disease in animals and clinical trials.

Intoduction: Mechanical complications from spinal fusion including implant loosening or junctional failure result in poor outcomes, particularly in osteoporotic patients. While the use of percutaneous vertebral augmentation with polymethylmethacrylate (PMMA) has been studied for augmentation of junctional levels to offset against kyphosis and failure, its deployment around existing loose screws or in failing surrounding bone as a salvage percutaneous procedure has been described in small case series and merits review. Research Question: How effective and safe is the use of PMMA as a salvage procedure for mechanical complications in failed spinal fusion?. Materials and Methods: Systematic search of online databases for clinical studies using this technique. Results: 11 studies were identified, only consisting of two case reports and nine case series. Consistent improvements were observed in pre- to post-operative VAS and with sustained improvements at final follow-up. The extra- or para-pedicular approach was the most frequent access trajectory. Most studies cited difficulties with visibility on fluoroscopy, using navigation or oblique views as a solution for this. Discussion and Conclusions: Percutaneous cementation at a failing screw-bone interface stabilises further micromotion with reductions in back pain. This rarely used technique is manifested by a low but increasing number of reported cases. The technique warrants further evaluation and is best performed within a multidisciplinary setting at a specialist centre. Notwithstanding that underlying pathology may not be addressed, awareness of this technique may allow an effective and safe salvage solution with minimal morbidity for older sicker patients.

Dose limiting cardiotoxicity remains a major limiting factor in the clinical use of several cancer chemotherapeutics including anthracyclines and the antimetabolite 5-fluorouracil (5-FU). Prior work has demonstrated that chemotherapeutics increase expression of R7 family regulator of G protein signaling (RGS) protein-binding partner Gβ5, which drives myocyte cytotoxicity. However, though several R7 family members are expressed in heart, the exact role of each protein in chemotherapy driven heart damage remains unclear. Here, we demonstrate that RGS11, downregulated in the human heart following chemotherapy exposure, possesses potent anti-apoptotic actions, in direct opposition to the actions of fellow R7 family member RGS6. RGS11 forms a direct complex with the apoptotic kinase CaMKII and stress responsive transcription factor ATF3 and acts to counterbalance the ability of CaMKII and ATF3 to trigger oxidative stress, mitochondrial dysfunction, cell death, and release of the cardiokine neuregulin-1 (NRG1), which mediates pathological intercommunication between myocytes and endothelial cells. Doxorubicin triggers RGS11 depletion in the murine myocardium, and cardiac-specific OE of RGS11 decreases doxorubicin-induced fibrosis, myocyte hypertrophy, apoptosis, oxidative stress, and cell loss and aids in the maintenance of left ventricular function. Conversely, RGS11 knockdown in heart promotes cardiac fibrosis associated with CaMKII activation and ATF3/NRG1 induction. Indeed, inhibition of CaMKII largely prevents the fibrotic remodeling resulting from cardiac RGS11 depletion underscoring the functional importance of the RGS11-CaMKII interaction in the pathogenesis of cardiac fibrosis. These data describe an entirely new role for RGS11 in heart and identify RGS11 as a potential new target for amelioration of chemotherapy-induced cardiotoxicity.

Objective: The gut hormone glucose-dependent insulinotropic polypeptide (GIP) stimulates beta cell function and improves glycemia through its incretin actions. GIP also regulates endothelial function and suppresses adipose tissue inflammation through control of macrophage activity. Activation of the GIP receptor (GIPR) attenuates experimental atherosclerosis and inflammation in mice, however whether loss of GIPR signaling impacts the development of atherosclerosis is uncertain. Methods: Atherosclerosis and related metabolic phenotypes were studied in Apoe−/−:Gipr−/− mice and in Gipr+/+ and Gipr−/− mice treated with an adeno-associated virus expressing PCSK9 (AAV-PCSK9). Bone marrow transplantation (BMT) studies were carried out using donor marrow from Apoe−/−:Gipr−/−and Apoe−/−:Gipr+/+mice transplanted into Apoe−/−:Gipr−/− recipient mice. Experimental endpoints included the extent of aortic atherosclerosis and inflammation, body weight, glucose tolerance, and circulating lipid levels, the proportions and subsets of circulating leukocytes, and tissue gene expression profiles informing lipid and glucose metabolism, and inflammation. Results: Body weight was lower, circulating myeloid cells were reduced, and glucose tolerance was not different, however, aortic atherosclerosis was increased in Apoe−/−:Gipr−/− mice and trended higher in Gipr−/− mice with atherosclerosis induced by AAV-PCSK9. Levels of mRNA transcripts for genes contributing to inflammation were increased in the aortae of Apoe−/−:Gipr−/− mice and expression of a subset of inflammation-related hepatic genes were increased in Gipr−/− mice treated with AAV-PCSK9. BMT experiments did not reveal marked atherosclerosis, failing to implicate bone marrow derived GIPR + cells in the control of atherosclerosis or aortic inflammation. Conclusions: Loss of the Gipr in mice results in increased aortic atherosclerosis and enhanced inflammation in aorta and liver, despite reduced weight gain and preserved glucose homeostasis. These findings extend concepts of GIPR in the suppression of inflammation-related pathophysiology beyond its classical incretin role in the control of metabolism.

A comprehensible, validated, and simple method was developed for the determination of Fe+3 ions in food samples. To accomplish this, Vitamin B12-functionalized biological silver nanoparticles (FAgNPs) were synthesised and employed. The test of sensitivity showed 2 mgL−1 as the limit of detection for Fe+3 ions by FAgNPs. The intra-day and inter-day recoveries of Fe+3 were observed in the range of 78–88% and 74–94%, respectively. Moreover, the procedure was successfully applied for Fe+3 ion detection in some cereals and commercially available baby food products. The application of FAgNPs-based methods showed high specificity and sensitivity, providing a promising strategy to detect low Fe+3 ion concentration in the range of 2–10 mgL−1. When compared to atomic absorption spectrophotometry, the detection efficiency of FAgNPs-based method was comparable and acceptable. The proposed methodology is a low-cost and portable nanoparticle-based technology for rapid assessment of Fe+3 ions with promising potential for practical implementation, beside being sustainable due to its biogenic nature.

Recently focus of studies on the periodic precipitation in gels is shifting from evaluation of its spatio-temporal characteristics of the self-organized patterns to that of as a novel and viable method of synthesis of hierarchical monodispersed micro and nanomaterials in a single reactor. One of the parameters that profoundly affect the morphology, shape, size, and self-organization in the chemical systems is the supersaturation of the participating species. The Matalon-Packter (MP) law correlates the effect of the concentration of invading electrolytes to the spatial patterning in the Liesegang system. Although concentration and supersaturation have quantitative relations, the implications of supersaturation on the spatial arrangement of the band are not entirely understood. The present paper deals with studies on the periodically precipitating Co(OH)2 in agar gel with respect to supersaturation of the participating reactants during the pattern formation. Varying inner and outer electrolytes concentrations were employed to determine spatial trends. Pattern image analysis was used to determine the precise location of the Liesegang bands. The supersaturation values showed a decreasing trend as the diffusion progressed outward. The present study led to the correlation between the supersaturation and the spacing coefficient.

The pathophysiological mechanism(s) driving non-alcoholic fatty liver disease, the most prevalent chronic liver disease globally, have yet to be fully elucidated. Here, we identify regulator of G protein signaling 6 (RGS6), up-regulated in the livers of NAFLD patients, as a critical mediator of hepatic steatosis, fibrosis, inflammation, and cell death. Human patients with high hepatic RGS6 expression exhibited a corresponding high inflammatory burden, pronounced insulin resistance, and poor liver function. In mice, liver-specific RGS6 knockdown largely ameliorated high fat diet (HFD)-driven oxidative stress, fibrotic remodeling, inflammation, lipid deposition and cell death. RGS6 depletion allowed for maintenance of mitochondrial integrity restoring redox balance, improving fatty acid oxidation, and preventing loss of insulin receptor sensitivity in hepatocytes. RGS6 is both induced by ROS and increases ROS generation acting as a key amplification node to exacerbate oxidative stress. In liver, RGS6 forms a direct complex with ATM kinase supported by key aspartate residues in the RGS domain and is both necessary and sufficient to drive hyperlipidemia-dependent ATM phosphorylation. pATM and markers of DNA damage (γH2AX) were also elevated in livers from NAFLD patients particularly in samples with high RGS6 protein content. Unsurprisingly, RGS6 knockdown prevented ATM phosphorylation in livers from HFD-fed mice. Further, RGS6 mutants lacking the capacity for ATM binding fail to facilitate palmitic acid-dependent hepatocyte apoptosis underscoring the importance of the RGS6-ATM complex in hyperlipidemia-dependent cell death. Inhibition of RGS6, then, may provide a viable means to prevent or reverse liver damage by mitigating oxidative liver damage.

Background and aim: Luteolin belongs to flavone group of flavonoids, present in many plants with potent antioxidant, anti-inflammatory and anti-proliferative effects. The objective of present study was to investigate protective effect of luteolin on injury induced inflammation via Monosodium urate (MSU) crystals induced and Acetaminophen (AMP) induced liver injury in rats. Experimental procedure: Protective effect of luteolin was observed by measurement of rat paw edema, lysosomal enzymes, antioxidants status and cytokine level. Measurement of uric acid level and neutrophil infiltration were done in AMP induced liver injury in rats. Luteolin was tested at 30 and 50 mg/kg doses and compare with colchicine. Results and conclusion: Luteolin significantly decreases paw edema in dose dependent manner compare to control group in MSU crystal-induced rats. Luteolin (50 mg/kg) was showed significant decrease in serum level of oxidative and lysosomal enzymes, proinflammatory cytokines i.e. tumor necrosis factor (TNF)-α (39.28 ± 3.17), interleukin (IL)-1β (12.07 ± 1.24), and IL-6 (24.72 ± 2.52) in MSU crystal-induced rats. In AMP induced liver injury, tissue uric acid level and myeloperoxidase were decreased significantly after treatment with luteolin as well as N-acetylcysteine. Serum level of liver enzymes was significantly reduced after treatment with luteolin. Histological observation of ankle joints and liver was support to protective effect of luteolin at both doses. In conclusion, luteolin showed anti-inflammatory effect through restoration of cytokine level, lysosomal enzymes level and antioxidants status. The reduction of liver tissue uric acid content may be one of the mechanisms for protective effect of luteolin. It can contribute to reduce injury induced inflammation. Keywords: Luteolin, Monosodium urate crystals, Acetaminophen, Colchicine, Anti-inflammatory

Objective: Glucose-dependent insulinotropic polypeptide (GIP) is secreted from the gut in response to nutrient ingestion and promotes meal-dependent insulin secretion and lipid metabolism. Loss or attenuation of GIP receptor (GIPR) action leads to resistance to diet-induced obesity through incompletely understood mechanisms. The GIPR is expressed in white adipose tissue; however, its putative role in brown adipose tissue (BAT) has not been explored. Methods: We investigated the role of the GIPR in BAT cells in vitro and in BAT-specific (GiprBAT−/−) knockout mice with selective elimination of the Gipr within the Myf5+ expression domain. We analyzed body weight, adiposity, glucose homeostasis, insulin and lipid tolerance, energy expenditure, food intake, body temperature, and iBAT oxygen consumption ex vivo. High-fat diet (HFD)-fed GiprBAT−/− mice were studied at room temperature (21 °C), 4 °C, and 30 °C ambient temperatures. Results: The mouse Gipr gene is expressed in BAT, and GIP directly increased Il6 mRNA and IL-6 secretion in BAT cells. Additionally, levels of thermogenic, lipid and inflammation mRNA transcripts were altered in BAT cells transfected with Gipr siRNA. Body weight gain, energy expenditure, and glucose and insulin tolerance were normal in HFD-fed GiprBAT−/− mice housed at room temperature. However, GiprBAT−/− mice exhibited higher body temperatures during an acute cold challenge and a lower respiratory exchange ratio and impaired lipid tolerance at 21 °C. In contrast, body weight was lower and iBAT oxygen consumption was higher in HFD-fed mice housed at 4 °C but not at 30 °C. Conclusions: The BAT GIPR is linked to the control of metabolic gene expression, fuel utilization, and oxygen consumption. However, the selective loss of the GIPR within BAT is insufficient to recapitulate the findings of decreased weight gain and resistance to obesity arising in experimental models with systemic disruption of GIP action. Keywords: Glucose-dependent insulinotropic polypeptide receptor, Brown adipose tissue, Thermogenesis, Energy expenditure, Obesity, Lipid metabolism

Objective: Administration of glucagon (GCG) or GCG-containing co-agonists reduces body weight and increases energy expenditure. These actions appear to be transduced by multiple direct and indirect GCG receptor (GCGR)-dependent mechanisms. Although the canonical GCGR is expressed in brown adipose tissue (BAT) the importance of BAT GCGR activity for the physiological control of body weight, or the response to GCG agonism, has not been defined. Methods: We studied the mechanisms linking GCG action to acute increases in oxygen consumption using wildtype (WT), Ucp1−/− and Fgf21−/− mice. The importance of basal GCGR expression within the Myf5+ domain for control of body weight, adiposity, glucose and lipid metabolism, food intake, and energy expenditure was examined in GcgrBAT−/− mice housed at room temperature or 4 °C, fed a regular chow diet (RCD) or after a prolonged exposure to high fat diet (HFD). Results: Acute GCG administration induced lipolysis and increased the expression of thermogenic genes in BAT cells, whereas knockdown of Gcgr reduced expression of genes related to thermogenesis. GCG increased energy expenditure (measured by oxygen consumption) both in vivo in WT mice and ex vivo in BAT and liver explants. GCG also increased acute energy expenditure in Ucp1−/− mice, but these actions were partially blunted in Ffg21−/− mice. However, acute GCG administration also robustly increased oxygen consumption in GcgrBAT−/− mice. Moreover, body weight, glycemia, lipid metabolism, body temperature, food intake, activity, energy expenditure and adipose tissue gene expression profiles were normal in GcgrBAT−/− mice, either on RCD or HFD, whether studied at room temperature, or chronically housed at 4 °C. Conclusions: Exogenous GCG increases oxygen consumption in mice, also evident both in liver and BAT explants ex vivo, through UCP1-independent, FGF21-dependent pathways. Nevertheless, GCGR signaling within BAT is not physiologically essential for control of body weight, whole body energy expenditure, glucose homeostasis, or the adaptive metabolic response to cold or prolonged exposure to an energy dense diet. Keywords: Glucagon, brown adipose tissue, Energy expenditure, Adiposity, Lipolysis, Thermogenesis

Excessive ingestion of the common analgesic acetaminophen (APAP) leads to severe hepatotoxicity. Here we identify G protein β5 (Gβ5), elevated in livers from APAP overdose patients, as a critical regulator of cell death pathways and autophagic signaling in APAP-exposed liver. Liver-specific knockdown of Gβ5 in mice protected the liver from APAP-dependent fibrosis, cell loss, oxidative stress, and inflammation following either acute or chronic APAP administration. Conversely, overexpression of Gβ5 in liver was sufficient to drive hepatocyte dysfunction and loss. In hepatocytes, Gβ5 depletion ameliorated mitochondrial dysfunction, allowed for maintenance of ATP generation and mitigated APAP-induced cell death. Further, Gβ5 knockdown also reversed impacts of APAP on kinase cascades (e.g. ATM/AMPK) signaling to mammalian target of rapamycin (mTOR), a master regulator of autophagy and, as a result, interrupted autophagic flux. Though canonically relegated to nuclear DNA repair pathways, ATM also functions in the cytoplasm to control cell death and autophagy. Indeed, we now show that Gβ5 forms a direct, stable complex with the FAT domain of ATM, important for autophosphorylation-dependent kinase activation. These data provide a viable explanation for these novel, G protein-independent actions of Gβ5 in liver. Thus, Gβ5 sits at a critical nexus in multiple pathological sequelae driving APAP-dependent liver damage.

Purpose: This study aimed to evaluate a combination of radiation therapy (RT), androgen deprivation therapy (ADT), and pexidartinib (colony-stimulating factor 1 receptor [CSF1R]) inhibitor in men with intermediate- and high-risk prostate cancer. CSF1R signaling promotes tumor infiltration and survival of tumor-associated macrophages, which in turn promote progression and resistance. Counteracting protumorigenic actions of tumor-associated macrophages via CSF1R inhibition may enhance therapeutic efficacy of RT and ADT for prostate cancer. Methods and Materials: In this phase 1 study, the treatment regimen consisted of pexidartinib (800 mg, administered as a split-dose twice daily) and ADT (both for a total of 6 months), and RT that was initiated at the start of month 3. RT volumes included the prostate and proximal seminal vesicles. The delivered dose was 7920 cGy (180 cGy per fraction) using intensity modulated RT with daily image guidance for prostate localization. The primary objective was to identify the maximum tolerated dose based on dose-limiting toxicities. Results: All 4 enrolled patients who were eligible to receive RT had T1 stage prostate cancer, 2 were intermediate risk, and 2 were high risk. The median age was 62.5 years, and the prostate-specific antigen levels were in the range 6.4 to 10.7 ng/mL. The patients’ individual Gleason scores were 3 + 3, 4 + 3, 4 + 4, and 4 + 5. All 4 patients reported ≥1 adverse events before RT. Grade 1 hypopigmentation was observed in 1 patient, and grade 3 pulmonary embolus in another. One patient experienced fatigue and joint pain, and another elevated amylase and pruritus (all grade 3 toxicities). Five of the 6 adverse events noted in 3 patients were all grade 3 toxicities attributable to pexidartinib, qualifying as dose-limiting toxicities and ultimately resulting in the study closure. Conclusions: The combination was not well tolerated and does not warrant further investigation in men with intermediate- and high-risk prostate cancer.

Social-cognitive difficulties can negatively impact interpersonal communication, shared social experience, and meaningful relationships. This pilot investigation examined the relationship between social-cognitive functioning and inflammatory markers in people with multiple sclerosis (MS) and demographically-matched healthy individuals. Additionally, we compared the immune marker profile in serum and urine-matched samples. Social cognitive functioning was objectively assessed using The Awareness of Social Inference Test – Short (TASIT-S) and subjectively assessed using self-reports of abilities in emotion recognition, emotional empathy, and cognitive theory of mind. In people with MS and healthy individuals, there were moderate-to-large negative relationships between pro-inflammatory biomarkers (serum IL-1β, IL-17, TNF-α, IP-10, MIP-1α, and urine IP-10, MIP-1β) of the innate immune system and social-cognitive functioning. In MS, a higher serum concentration of the anti-inflammatory marker IL-1ra was associated with better social-cognitive functioning (i.e., self-reported emotional empathy and TASIT-S sarcasm detection performance). However, there were mixed findings for anti-inflammatory serum markers IL-4 and IL-10. Overall, our findings indicate a relationship between pro-inflammatory cytokines and social-cognitive abilities. Future studies may provide greater insight into biologically-derived inflammatory processes, sickness behaviour, and their connection with social cognition.

Objective: Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-like peptide-1 (GLP-1) are incretin hormones that exert overlapping yet distinct actions on islet β-cells. We recently observed that GIP, but not GLP-1, upregulated islet expression of Transcription Factor 7 (TCF7), a gene expressed in immune cells and associated with the risk of developing type 1 diabetes. TCF7 has also been associated with glucose homeostasis control in the liver. Herein we studied the relative metabolic importance of TCF7 expression in hepatocytes vs. islet β-cells in mice. Methods: Tcf7 expression was selectively inactivated in adult mouse hepatocytes using adenoviral Cre expression and targeted in β-cells using two different lines of insulin promoter-Cre mice. Glucose homeostasis, plasma insulin and triglyceride responses, islet histology, hepatic and islet gene expression, and body weight gain were evaluated in mice fed regular chow or high fat diets. Tcf7 expression within pancreatic islets and immune cells was evaluated using published single cell RNA-seq (scRNA-seq) data, and in islet RNA from immunodeficient Rag2−/−Il2rg−/− mice. Results: Reduction of hepatocyte Tcf7 expression did not impair glucose homeostasis, lipid tolerance or hepatic gene expression profiles linked to control of metabolic or immune pathways. Similarly, oral and intraperitoneal glucose tolerance, plasma insulin responses, islet histology, body weight gain, and insulin tolerance were not different in mice with targeted recombination of Tcf7 in insulin-positive β-cells. Surprisingly, islet Tcf7 mRNA transcripts were not reduced in total islet RNA containing endocrine and associated non-endocrine cell types from Tcf7βcell−/− mice, despite Cre-mediated recombination of islet genomic DNA. Furthermore, glucose tolerance was normal in whole body Tcf7−/− mice. Analysis of scRNA-seq datasets localized pancreatic Tcf7 expression to islet progenitors during development, and immune cells, but not within differentiated islet β-cells or endocrine lineages within mature islets. Moreover, the expression of Tcf7 was extremely low in islet RNA from Rag2−/−Il2rg−/− mice and, consistent with expression within immune cells, Tcf7 was highly correlated with levels of Cd3g mRNA transcripts in RNA from wild type mouse islets. Conclusions: These findings demonstrate that Tcf7 expression is not a critical determinant of glucose homeostasis in mice. Moreover, the detection of Tcf7 expression within islet mRNA is attributable to the expression of Tcf7 RNA in islet-associated murine immune cells, and not in islet β-cells.

Both perchlorate and black carbon (BC) are known for their common source of origin (i.e. burning processes, especially fireworks display), yet to our knowledge no study has focused on the effect of perchlorate (ClO4-) on the mobility of black carbon. The present study focuses on the effect of presence of perchlorate at a concentration ranging from 0.1, 0.5, 1.0, 3.0 and 5.0 ​mg/L on the mobility and aggregation of black carbon (soot) particles in a porous medium. The hydrodynamic diameter of soot particles increased with increasing perchlorate concentration, and gradually decreased due to self-decay of perchlorate. The results are in accordance with coagulation theory, which suggest that above critical ionic strength, aggregation is independent of electrolyte concentration. Column-based microscopic transport studies simulating the mobility of soot particles in the presence of metals and perchlorate with varying environmental parameters will be helpful in development of the fate and transport models. Further, more precise observation with changing perchlorate concentrations is possible using Quartz Crystal Microbalance with Dissipation (QCM-D).

Disease detection is a time-consuming and essential task in the medical diagnosis system. Machine learning plays a vital role in predicting and identifying diseases at various stages. It is a very random and timely method for analyzing disease using clinical and laboratory signs and assists medical representatives in developing a more effective diagnostic strategy for such diseases. For example, swine flu, a contagious illness caused by influenza viruses, including the H1N1 virus, infects the respiratory tract of pigs, causing a barking cough, decreased appetite, nasal secretions, and uncontrollable behaviour. Cloud computing and the Internet of things help the medical sector by processing health information in ultra-low delay so that effective decisions can be taken timely. In this paper, a fog-centric IoT-based smart healthcare support service for monitoring and controlling the Swine Flu virus epidemic is proposed. The proposed framework utilizes the concept of fog computing for delay-sensitive applications. Furthermore, a hybrid classifier is used to classify the swine flu patient at an early stage and generate alerts to the health officials and patients' guardians. In the experimental setup, the iFogSim simulator is used to mimic the IoT devices and fog nodes for evaluating various parameters such as accuracy, energy, and Latency, whereas WEKA is used for developing a hybrid classifier. Results demonstrate the benefits of combining fog and cloud computing services to achieve higher network bandwidth reliability, a higher level of operation, and a shorter response time while generating real-time notifications, as compared to an existing cloud-only model.

In this work, Pseudomonas stutzeri was used for the optimum biogenic synthesis of antibacterial silver nanoparticles (AgNPs) which were applied for colorimetric detection of platinum ions (Pt+2). The optimum synthesis conditions were 2 mM AgNO3, pH 9 and incubation at 60 °C for 24 h. The FTIR spectra indicated that biomolecules such as amino acids, proteins or enzymes from P. stutzeri were involved in the synthesis of AgNPs in the size range of 10−50 nm. Among the various metal ions tested and screened initially, the colloidal AgNPs probe-based colorimetric assay selectively detected Pt+2 with 50 ppm as the limit of detection (LOD). The assay demonstrated in the present study quantitatively recovered Pt+2 in the range of 70–150 % with good accuracy and precision. Further, the test of antibacterial activity of AgNPs alone, and in combination with ampicillin showed excellent activity against four of the six tested bacteria. Keywords: Silver nanoparticles, Platinum, Colorimetric detection, Limit of detection, Antibacterial activity

Over expression of 11β-HSD 1 in key metabolic tissues is related to the development of type 2 diabetes, obesity, hypertension and metabolic syndrome. Nephrotoxicity of corosolic acid (selective inhibitor of 11β-HSD 1) is recently reported, which is one of the major drawback. Therefore, it is of great interest to find out the selective 11β-HSD 1 inhibitors without nephrotoxicity. Using crystal structures of 11β-HSD 1 in complex with inhibitors as a source of structural information, a combined structure-based virtual screening approach followed by PASS toxicity prediction, Lipinski’s rule and ADME prediction was implemented to find out the potent and selective 11 β-HSD 1 analog of corosolic acid without nephrotoxicity. Two compounds with NCBI compound identification number CID59752459 (Genins of Asiatic acid) and CID 119034 (Asiatic acid) were found to be selective for the 11β-HSD 1 enzyme without nephrotoxicity which comply with Lipinski’s rule and ADME parameter defined for human use. However, none of the hits inhibited 11β-HSD 2 at 100 μM indicating their selectivity against 11β-HSD 1.

Current medical countermeasures for organophosphate (OP)-induced status epilepticus (SE) are not effective in preventing long-term morbidity and there is an urgent need for improved therapies. Rat models of acute intoxication with the OP, diisopropylfluorophosphate (DFP), are increasingly being used to evaluate therapeutic candidates for efficacy in mitigating the long-term neurologic effects associated with OP-induced SE. Many of these therapeutic candidates target neuroinflammation and oxidative stress because of their implication in the pathogenesis of persistent neurologic deficits associated with OP-induced SE. Critical to these efforts is the rigorous characterization of the rat DFP model with respect to outcomes associated with acute OP intoxication in humans, which include long-term electroencephalographic, neurobehavioral, and neuropathologic effects, and their temporal relationship to neuroinflammation and oxidative stress. To address these needs, we examined a range of outcomes at later times post-exposure than have previously been reported for this model. Adult male Sprague-Dawley rats were given pyridostigmine bromide (0.1 mg/kg, im) 30 min prior to administration of DFP (4 mg/kg, sc), which was immediately followed by atropine sulfate (2 mg/kg, im) and pralidoxime (25 mg/kg, im). This exposure paradigm triggered robust electroencephalographic and behavioral seizures that rapidly progressed to SE lasting several hours in 90% of exposed animals. Animals that survived DFP-induced SE (~70%) exhibited spontaneous recurrent seizures and hyperreactive responses to tactile stimuli over the first 2 months post-exposure. Performance in the elevated plus maze, open field, and Pavlovian fear conditioning tests indicated that acute DFP intoxication reduced anxiety-like behavior and impaired learning and memory at 1 and 2 months post-exposure in the absence of effects on general locomotor behavior. Immunohistochemical analyses revealed significantly increased expression of biomarkers of reactive astrogliosis, microglial activation and oxidative stress in multiple brain regions at 1 and 2 months post-DFP, although there was significant spatiotemporal heterogeneity across these endpoints. Collectively, these data largely support the relevance of the rat model of acute DFP intoxication as a model for acute OP intoxication in the human, and support the hypothesis that neuroinflammation and/or oxidative stress represent potential therapeutic targets for mitigating the long-term neurologic sequelae of acute OP intoxication.

Statistically designed experiments were used to optimize the production of arginine deiminase (ADI) by Pseudomonas putida KT2440 in batch culture. A Plackett-Burman design involving eleven factors showed that ADI production was most influenced by the initial pH and the initial concentrations of glucose and yeast extract. A central composite experimental design showed that the optimal values of these factors were 8.0, 10 g/L and 12.5 g/L, respectively. The other components of the optimal culture medium were bacto peptone 7.5 g/L, Triton X–100 0.30% (v/v), and arginine 3 g/L, for a culture temperature of 25 °C. Compared with the basal medium, the ADI activity in the optimized medium had nearly 4.5-fold increase (4.31 U/mL). The optimized medium was then used for a further study of ADI production in a 14 L stirred tank bioreactor. The agitation speed and the aeration rates were varied to determine suitable values of these variables.

Background: Sleep disturbances and decline in the physical functionality are common conditions associated with aging. Pharmacological treatment of sleep disturbances can be associated with various adverse effects. Short term trials of Yoga on sleep have shown beneficial effects. Objectives: To evaluate the effect of long-term Yoga exercises on sleep quality and quality of life (QOL) in the elderly. Materials and Methods: This was a cross-sectional study in which data were collected from elderly people aged 60 years or more living in Nagpur city. We employed two types of survey questionnaires: Pittsburgh sleep quality index (PSQI) and QOL Leiden-Padua (LEIPAD) Questionnaire. A total of 65 elderly men and women who signed an informed consent and completed questionnaires were included in the study. Sleep quality score PSQI and QOL (LEIPAD Questionnaire) score of the study group were evaluated and compared with the control group using Mann-Whitney U test. Results: Total PSQI score in Yoga group was lower than that of the control group. Also various QOL scores of the Yoga groups were higher than the control group. Conclusion: Addition of regular Yoga exercises in the daily routine of elderly people can help to achieve good sleep quality as well as improve the QOL.

Gunshot injuries are rather serious but uncommon type of trauma in India. A 45-year-old male was presented with gunshot (pellets) embedded in the maxillofacial area for 22 years. There is no consensus in the literature whether to attempt their removal or leave them in situ. Our patient had no long-term sequela like infection, fistula formation, carcinogenesis or metal poisoning to date except for chill feeling on cold days. Management of this patient presented a dilemma in treatment in view of the effects of foreign bodies in the maxillofacial area. Key words: Maxillofacial injuries; Wounds, gunshot; Firearms