Community-developed checklists for publishing images and image analyses.

Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data.

Antifibrotic effect of the P2X7 receptor antagonist A740003 against acute myocardial infarction-induced fibrotic remodelling.

Post-acute myocardial infarction (AMI) fibrosis is a pathophysiologic process characterised by activation of the profibrotic mediator, transforming growth factor-ß (TGF-ß). AMI is associated with a substantial increase in the levels of extracellular adenosine triphosphate (eATP), which acts on the purinergic P2X7-receptor (P2X7-R) and triggers an inflammatory response that contributes to myocardial fibrotic remodelling. P2X7-R has been implicated in several cardiovascular diseases; however, its role in the regulation of cardiac fibrosis remains unclear. Therefore, the current study aimed to determine the effect of the P2X7-R antagonist, A740003, on post-AMI fibrosis, via the profibrotic TGF-ß1/Smad signalling pathway, and elucidate whether its effect is mediated via the modulation of GSK-3ß. AMI was induced by surgical ligation of the left anterior descending coronary artery, Thereafter, animals were divided into groups: sham control, MI-untreated, MI-vehicle, and MI-A740003 (50 mg/kg/day) and treated for seven days accordingly. The heart weight/body weight ratio of untreated-ligated rats significantly increased by 15.1 %, creatine kinase-MB (CK-MB) significantly increased by 40 %, troponin-I levels significantly increased by 25.4 %, and lactate dehydrogenase significantly increased by 47.2 %, indicating myocardial damage confirmed by morphological changes and massive cardiac fibrosis. The protein expression of cardiac fibronectin, TGF-ß1, and p-Smad2 were also upregulated by 143 %, 40 %, and 8 %, respectively, indicating cardiac fibrosis. The treatment of ligated rats with A740003 led to improvement in all the above-mentioned parameters. Overall, A740003 exhibits potential cardio-protective effects on post-AMI fibrotic remodelling in the animal model of AMI through P2X7-R blockade, possibly by downregulating the profibrotic TGF-ß1/Smad signalling pathway and restoring GSK-3ß phosphorylation. Altogether, treatment with A740003 could serve as a new cardioprotective strategy to attenuate post-AMI fibrotic remodelling.

Transcriptomic and Proteomic Analysis Reveals the Potential Role of RBMS1 in Adipogenesis and Adipocyte Metabolism.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. The dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA-binding motif single-stranded interacting protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. RBMS1 polymorphism has been shown to be associated with obesity and type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of the differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in the adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

Distinct Mechanisms of Cytotoxicity in Novel Nitrogenous Heterocycles: Future Directions for a New Anti-Cancer Agent.

Electron-rich, nitrogenous heteroaromatic compounds interact more with biological/cellular components than their non-nitrogenous counterparts. The strong intermolecular interactions with proteins, enzymes, and receptors confer significant biological and therapeutic properties to the imidazole derivatives, giving rise to a well-known and extensively used range of therapeutic drugs used for infections, inflammation, and cancer, to name a few. The current study investigates the anti-cancer properties of fourteen previously synthesized nitrogenous heterocycles, derivatives of imidazole and oxazolone, on a panel of cancer cell lines and, in addition, predicts the molecular interactions, pharmacokinetic and safety profiles of these compounds. METHOD: The MTT and CellTiter-Glo® assays were used to screen the imidazole and oxazolone derivatives on six cancer cell lines: HL60, MDA-MB-321, KAIMRC1, KMIRC2, MCF-10A, and HCT8. Subsequently, in vitro tubulin staining and imaging were performed, and the level of apoptosis was measured using the Promega ApoTox-Glo® triplex assay. Furthermore, several computational tools were utilized to investigate the pharmacokinetics and safety profile, including PASS Online, SEA Search, the QikProp tool, SwissADME, ProTox-II, and an in silico molecular docking study on tubulin to identify the critical molecular interactions. RESULTS: In vitro analysis identified compounds 8 and 9 to possess the most significant potent cytotoxic activity on the HL60 and MDA-MB-231 cell lines, supported by PASS Online anti-cancer predictions with pa scores of 0.413 and 0.434, respectively. In addition, compound 9 induced caspase 3/7 dependent-apoptosis and interfered with tubulin polymerization in the MDA-MB-231 cell line, consistent with in silico docking results, identifying binding similarity to the native ligand colchicine. All the derivatives, including compounds 8 and 9, had acceptable pharmacokinetics; however, the safety profile was suboptimal for all the tested derivates except compound 4. CONCLUSION: The imidazole derivative compound 9 is a promising anti-cancer agent that switches on caspase-dependent apoptotic cell death and modulates microtubule function. Therefore, it could be a lead compound for further drug optimization and development.

Surfactant modified waste ash for the removal of chloro and nitro group substituted benzene from wastewater.

A surfactant-modified coal fly ash was developed as a multifunctional adsorbent for the removal of organic pollutants from wastewater. Sodium dodecyl sulfate (SDS) was used to modify the surface of coal fly ash (CFA). The modified CFA was characterized using scanning electron microscopy (SEM), surface porosity analyzer, thermogravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy. The results showed that loading CFA with SDS not only improved the functionality and surface morphology of the raw ash for the adsorption of organic pollutants, but also enhanced its thermal stability. The efficiency of the modified fly ash was tested in terms of removal of two non-polar organic pollutants namely chlorobenzene (CB) and nitrobenzene (NB) from aqueous phase. The maximum uptake capacity of chlorobenzene and nitrobenzene with SDS-modified coal fly ash (SCFA) was 225 mg/g and 90 mg/g, respectively. The kinetic analysis was done by controlled kinetic models, i.e., pseudo first and second order kinetic models. The results showed that adsorption of CB and NB onto SCFA followed a pseudo second order kinetic model. The adsorption of chlorobenzene was exothermic over the modified adsorbent while nitrobenzene showed an endothermic behavior. The isotherm analysis depicted the multilayer adsorption of both pollutants onto the surface of the surfactant modified adsorbent. This work has shown that surface modification using surfactants can be a viable option to enhance the adsorption capacity of fly ash for pollutants removal.

Proteomics Profiling of KAIMRC1 in Comparison to MDA-MB231 and MCF-7.

Proteomics characterization of KAIMRC1 cell line, a naturally immortalized breast cancer cells, is described in comparison to MCF-7 and MDA-MB-231 breast cancer cells. Quantitative proteomics analysis using the tandem mass tag (TMT)-labeled technique in conjunction with the phosphopeptide enrichment method was used to perform comparative profiling of proteins and phosphoproteins in the three cell lines. In total, 673 proteins and 33 Phosphoproteins were differentially expressed among these cell lines. These proteins are involved in several key cellular pathways that include DNA replication and repair, splicing machinery, amino acid metabolism, cellular energy, and estrogen signaling pathway. Many of the differentially expressed proteins are associated with different types of tumors including breast cancer. For validation, 4 highly significant expressed proteins including S-methyl-5'-thioadenosine phosphorylase (MTAP), BTB/POZ domain-containing protein (KCTD12), Poly (ADP-ribose) polymerase 1 (PARP 1), and Prelamin-A/C were subjected to western blotting, and the results were consistent with proteomics analysis. Unlike MCF-7 and MDA-MB-231, KAIMRC1 showed different phospho- and non-phosphoproteomic phenotypes which make it a potential model to study breast cancer.

Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model.

The axon initial segment (AIS), the site of action potential initiation in neurons, is a critical determinant of neuronal excitability. Growing evidence indicates that appropriate recruitment of the AIS macrocomplex is essential for synchronized firing. However, disruption of the AIS structure is linked to the etiology of multiple disorders, including autism spectrum disorder (ASD), a condition characterized by deficits in social communication, stereotyped behaviors, and very limited interests. To date, a complete understanding of the molecular components that underlie the AIS in ASD has remained elusive. In this research, we examined the AIS structure in a BTBR T+Itpr3tf/J mouse model (BTBR), a valid model that exhibits behavioral, electrical, and molecular features of autism, and compared this to the C57BL/6J wild-type control mouse. Using Western blot studies and high-resolution confocal microscopy in the prefrontal frontal cortex (PFC), our data indicate disrupted expression of different isoforms of the voltage-gated sodium channels (NaV) at the AIS, whereas other components of AIS such as ankyrin-G and fibroblast growth factor 14 (FGF14) and contactin-associated protein 1 (Caspr) in BTBR were comparable to those in wild-type control mice. A Western blot assay showed that BTBR mice exhibited a marked increase in different sodium channel isoforms in the PFC compared to wild-type mice. Our results provide potential evidence for previously undescribed mechanisms that may play a role in the pathogenesis of autistic-like phenotypes in BTBR mice.

Nuclear Receptors Are Differentially Expressed and Activated in KAIMRC1 Compared to MCF7 and MDA-MB231 Breast Cancer Cells.

We recently established a KAIMRC1 cell line that has unique features compared to the known breast cancer cell lines, MCF7 and MDA-MB231. To characterize it further, we investigated the expression profile of nuclear receptors and their respective co-factors in these cell lines. We confirm that in contrast to the triple negative cell line MDA-MB231, the MCF7 and KAIMRC1 are estrogen receptor alpha (ERa) and progesterone receptor alpha (PRa) positive, with significant lower expression of these receptors in KAIMRC1. KAIMRC1 cell is a vitamin D receptor (VDR) negative and V-ErbA-Related Protein 2 (EAR2) positive in contrast to MCF7 and MDA-MB231. Remarkably, the histone deacetylases (HDACs) are highly expressed in KAIRMC1 with HDAC6 and HDAC 7 are exclusively expressed in KAIMRC1 while thyroid hormone receptor-associated protein 80 (TRAP80), telomeric DNA binding protein 1 (TBP1) and TGF-beta receptor interacting protein (TRIP1) are absent in KAIMRC1 but present in MCF7 and MDA-MB231. In a luciferase reporter assay, the ERa coexpression is needed for estrogen receptor element (ERE)-luciferase activation by estradiol in KAIMRC1 but not in MCF7. The co-expression of exogenous Liver X receptor alpha (LXRa)/retinoid X receptor alpha (RXRa) are necessary for LXR responsive element (LXRE) activation by the GW3696 in the three cell lines. However, the activity of peroxisome proliferator-activated receptor response element (PPARE)-tk-luciferase reporter increased when peroxisome proliferator-activated receptors alpha (PPARa)/RXRa were coexpressed but the addition of PPARa agonist (GW7647) did not stimulate further the reporter. The signal of the PPARE reporter increased in a dose-dependent manner with rosiglitazone (PPARg agonist) in KAIMRC1, MCF7, and MDA-MB231 when the proliferator-activated receptors gamma (PPARg)/RXRa receptors were cotransfected. Retinoic acid-induced activation of retinoic acid receptor response element (RARE)-tk-luciferase is dependent on exogenous expression of retinoic acid receptor alpha (RARa)/RXRa heterodimer in MDA-MB 231 but not in MCF7 and KAIMRC1 cell lines. In the three cell lines, Bexarotene-induced retinoid X receptor response element (RXRE)-luciferase reporter activation was induced only if the RXRa/LXRa heterodimer were co-expressed. The vitamin D receptor response element (VDRE)-luciferase reporter activity showed another distinct feature of KAIMRC1, where only co-expression of exogenous vitamin D receptor (VDR)/RXRa heterodimer was sufficient to reach the maximum rate of activation of VDRE reporter. In the proliferation assay, nuclear receptors ligands showed a distinct effect on KAIMRC1 compared to MCF7 and MDA-MB231. Growth inhibition effects of used ligands suggest that KAIMRC1 correlate more closely to MDA-MB231 than MCF7. Vitamin D3, rosiglitazone, novel RXR compound (RXRc) and PPARa compound (GW6471) have the most profound effects. In conclusion, we showed that nuclear receptors are differentially expressed, activated and also their ligand produced distinct effects in KAIMRC1 compared to MCF7 and MDA-MB231. This finding gives us confidence that KAIMRC1 has a unique biological phenotype.

Characterization and hepatoprotective evaluation of sesquiterpenes and diterpenes from the aerial parts of Juniperus sabina L.

Previously, we reported on the hepatoprotective activity of the total extract of Juniperus sabina L. against CCl4 induced liver toxicity in experimental animals. Biologically directed phytochemical study was conducted to identify the active compounds. Male Wistar rats and the standard drug silymarin were used in the study. Hepatoprotective activity was evaluated via serum biochemical parameters such as aspartate amino transferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin. Tissue parameters including non-protein sulfhydryl groups (NP-SH), malonaldehyde (MDA) and total protein (TP) were also determined. Histopathological study was conducted utilizing Mayer's hematoxylin stain, Periodic Acid Schiff - Hematoxylin (PAS-H) and Masson trichrome technique on light microscope. Electron microscope images were also generated for the study. The activity of the total extract was trapped to the petroleum ether fraction after liquid-liquid fractionation where 51% reduction in the levels of AST, bilirubin and 44% in the levels of ALT were observed. Chromatographic purification of the petroleum ether fraction resulted in the isolation of nine compounds namely: trans-calamenene (1), cadalene (cadalin) (2), epi-cubenol (3), manool (4), calamenene-10ß-ol (5), calamenene-10α-ol (6), 4-epi-abietic acid (7), sandaracopimaric acid (8) and isopimaric acid (9). Compounds 1-3, 5 and 6 are belonging to cadinane sesquiterepenes, while compounds 4, 7-9 were of diterpene skeleton. The major compounds were tested for their hepatoprotective effect. Compounds 3 showed marked improvement in the levels of AST and ALT, compound 4 was effective in improving the levels of AST, ALT, GGT, ALP and bilirubin, while compound 7 showed significant improvement in GGT, ALP and bilirubin levels.

Quantitative MR thermometry based on phase-drift correction PRF shift method at 0.35 T.

BACKGROUND: Noninvasive magnetic resonance thermometry (MRT) at low-field using proton resonance frequency shift (PRFS) is a promising technique for monitoring ablation temperature, since low-field MR scanners with open-configuration are more suitable for interventional procedures than closed systems. In this study, phase-drift correction PRFS with first-order polynomial fitting method was proposed to investigate the feasibility and accuracy of quantitative MR thermography during hyperthermia procedures in a 0.35 T open MR scanner. METHODS: Unheated phantom and ex vivo porcine liver experiments were performed to evaluate the optimal polynomial order for phase-drift correction PRFS. The temperature estimation approach was tested in brain temperature experiments of three healthy volunteers at room temperature, and in ex vivo porcine liver microwave ablation experiments. The output power of the microwave generator was set at 40 W for 330 s. In the unheated experiments, the temperature root mean square error (RMSE) in the inner region of interest was calculated to assess the best-fitting order for polynomial fit. For ablation experiments, relative temperature difference profile measured by the phase-drift correction PRFS was compared with the temperature changes recorded by fiber optic temperature probe around the microwave ablation antenna within the target thermal region. RESULTS: The phase-drift correction PRFS using first-order polynomial fitting could achieve the smallest temperature RMSE in unheated phantom, ex vivo porcine liver and in vivo human brain experiments. In the ex vivo porcine liver microwave ablation procedure, the temperature error between MRT and fiber optic probe of all but six temperature points were less than 2 °C. Overall, the RMSE of all temperature points was 1.49 °C. CONCLUSIONS: Both in vivo and ex vivo experiments showed that MR thermometry based on the phase-drift correction PRFS with first-order polynomial fitting could be applied to monitor temperature changes during microwave ablation in a low-field open-configuration whole-body MR scanner.

P19 Cells as a Model for Studying the Circadian Clock in Stem Cells before and after Cell Differentiation.

In mammals, circadian rhythmicity is sustained via a transcriptional/translational feedback loop referred to as the canonical molecular circadian clock. Circadian rhythm is absent in undifferentiated embryonic stem cells; it begins only after differentiation. We used pluripotent P19 embryonal carcinoma stem cells to check the biological clock before and after differentiation into neurons using retinoic acid. We show that the central clock genes ARNTL (Bmal), Per2 and Per3, and the peripheral clock genes Rev-erb-α and ROR-α, oscillate before and after differentiation, as does the expression of the neuronal differentiation markers Hes5, ß-3-tubulin (Tubb3) and Stra13, but not Neurod1. Furthermore, the known clock-modulating compounds ERK, EGFR, Pi3K, p38, DNA methylation and Sirtiun inhibitors, in addition to Rev-erb-α ligands, modulate the expression of central and peripheral clock genes. Interestingly Sirtinol, Sirt1 and Sirt2 inhibitors had the greatest significant effect on the expression of clock genes, and increased Hes5 and Tubb3 expression during neuronal differentiation. Our findings reveal a new frontier of circadian clock research in stem cells: contrary to what has been published previously, we have shown the clock to be functional and to oscillate, even in undifferentiated stem cells. Modulating the expression of clock genes using small molecules could affect stem cell differentiation.

Evaluation of the hepatoprotective effect of combination between hinokiflavone and Glycyrrhizin against CCl4 induced toxicity in rats.

Liver diseases are one of the fatal syndromes due to the vital role of the liver. Most of the effective treatment of liver conditions are of natural origin. Silymarin (SI) is the standard drug used for treatment of impaired liver functions. Two natural compounds possessing promising liver protection and with different chemical structures namely; the bioflavonoid hinokiflavone (HF) isolated from Junipers phoenicea family Cupressaceae and the sweet saponin Glycyrrhizin (GL) present in Glycyrrhiza glabra (liquorice) were selected for the current study. Since the two compounds are of different nature, they may act by different mechanisms and express synergistic effect. Combination of the two compounds using to dose levels were challenged with single doses of HF, GL and SI as well. The comparison was monitored via measuring serum biochemical parameters including, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltranspeptidase (GGT), alkaline phosphatase (ALP) and total bilirubin, tissue parameters such as MDA, NP-SH and TP, histopathological study using light and electron microscope. Protective effect on kidney was also monitored histopathologically and biochemically through observing the levels of LDH, creatinine, creatinine-kinase, urea and uric acid. The combinations of HF and GL showed protective effect more than the used single doses of HF and GL alone. However, SI was superior to the used combination in the two used doses in all the measured parameters. The liver and kidney cells appearance under normal and electron microscope showed that SI treated groups showed almost normal cells with slight toxic signs. Cells from group treated with the higher doses of the combination of HF and GL showed slight signs of intoxication under light and electron microscope indicating good level of protection. Although the combination of HF and GL expressed good protection in the higher dose, however, the combination did not exceed the protective effect of SI.

Biological impact of advanced glycation endproducts on estrogen receptor-positive MCF-7 breast cancer cells.

Diabetes mellitus potentiates the risk of breast cancer. We have previously described the pro-tumorigenic effects of advanced glycation endproducts (AGEs) on estrogen receptor (ER)-negative MDA-MB-231 breast cancer cell line mediated through the receptor for AGEs (RAGE). However, a predominant association between women with ER-positive breast cancer and type 2 diabetes mellitus has been reported. Therefore, we have investigated the biological impact of AGEs on ER-positive human breast cancer cell line MCF-7 using in vitro cell-based assays including cell count, migration, and invasion assays. Western blot, FACS analyses and quantitative real time-PCR were also performed. We found that AGEs at 50-100µg/mL increased MCF-7 cell proliferation and cell migration associated with an enhancement of pro-matrix metalloproteinase (MMP)-9 activity, without affecting their poor invasiveness. However, 200µg/mL AGEs inhibited MCF-7 cell proliferation through induction of apoptosis indicated by caspase-3 cleavage detected using Western blotting. A phospho-protein array analysis revealed that AGEs mainly induce the phosphorylation of extracellular-signal regulated kinase (ERK)1/2 and cAMP response element binding protein-1 (CREB1), both signaling molecules considered as key regulators of AGEs pro-tumorigenic effects. We also showed that AGEs up-regulate RAGE and ER expression at the protein and transcript levels in MCF-7 cells, in a RAGE-dependent manner after blockade of AGEs/RAGE interaction using neutralizing anti-RAGE antibody. Throughout the study, BSA had no effect on cellular processes. These findings pave the way for future studies investigating whether the exposure of AGEs-treated ER-positive breast cancer cells to estrogen could lead to a potentiation of breast cancer development and progression.

Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1.

BACKGROUND: Breast cancer is one of the most common cancer and a leading cause of death in women. Up to date the most commonly used breast cancer cell lines are originating from Caucasians or Afro-Americans but rarely cells are being derived from other ethnic groups. Here we describe for the first time the establishment of a naturally transformed breast cancer cell line, KAIMRC1 from an Arab woman of age 62 suffering from stage IIB breast cancer (T2N1M0). Moreover, we have characterized these cells for the biological and molecular markers, induction of MAPK pathways as well as its response to different commercially available drugs and compounds. METHODS: Breast cancer tissue sections were minced and cultured in media for several weeks. KAIMRC1 cells were successfully isolated from one of the primary breast tumor tissue cultures without any enzymatic digestion. To study the growth characteristics of the cells, wound healing assay, clonogenic assay, cell proliferation assays and live cell time-lapse microscopy was performed. Karyotyping, Immunophenotyping and molecular pathway specific compound treatment was also performed. A selective breast cancer gene expression panel was used to identify genes involved in the signal transduction dysregulation and malfunction of normal biological processes during breast carcinogenesis. RESULTS: These cells are ER/PR-positive and HER2-negative. The epithelial nature of these cells was confirmed by flow cytometry analysis using epithelial cell markers. They are cuboidal in shape and relatively smaller in size as compared to established cell lines, MCF-7, MDA MB-231 and the normal breast cell line, MCF-10A. In normal cell culture conditions these cells showed the capability of growing both in monolayer as well as in 3-D conformation. They showed a doubling time in vitro of approximately 24 h. They exhibit a modal karyotype of 58-63,X with abnormalities in a couple of chromosomes. KAIMRC1 cells were found to be more responsive to drug treatment in vitro in comparison to the established MDA MB-231 and MCF-7 cell lines. CONCLUSIONS: In conclusion we have isolated and characterized a new naturally immortalized breast cell line, KAIMRC1 with a potential to play a key role in opening up novel avenues towards the understanding of breast carcinoma.

Motor-related brain abnormalities in HIV-infected patients: a multimodal MRI study.

PURPOSE: It is generally believed that HIV infection could cause HIV-associated neurocognitive disorders (HAND) across a broad range of functional domains. Some of the most common findings are deficits in motor control. However, to date no neuroimaging studies have evaluated basic motor control in HIV-infected patients using a multimodal approach. METHODS: In this study, we utilized high-resolution structural imaging and task-state functional magnetic resonance imaging (fMRI) to assess brain structure and motor function in a homogeneous cohort of HIV-infected patients. RESULTS: We found that HIV-infected patients had significantly reduced gray matter (GM) volume in cortical regions, which are involved in motor control, including the bilateral posterior insula cortex, premotor cortex, and supramarginal gyrus. Increased activation in bilateral posterior insula cortices was also demonstrated by patients during hand movement tasks compared with healthy controls. More importantly, the reduced GM in bilateral posterior insula cortices was spatially coincident with abnormal brain activation in HIV-infected patients. In addition, the results of partial correlation analysis indicated that GM reduction in bilateral posterior insula cortices and premotor cortices was significantly correlated with immune system deterioration. CONCLUSION: This study is the first to demonstrate spatially coincident GM reduction and abnormal activation during motor performance in HIV-infected patients. Although it remains unknown whether the brain deficits can be recovered, our findings may yield new insights into neurologic injury underlying motor dysfunction in HAND.

Magnetic Fluorescent Nanoformulation for Intracellular Drug Delivery to Human Breast Cancer, Primary Tumors, and Tumor Biopsies: Beyond Targeting Expectations.

We report the development of a chemotherapeutic nanoformulation made of polyvinylpyrrolidone-stabilized magnetofluorescent nanoparticles (Fl-PMNPs) loaded with anticancer drugs as a promising drug carrier homing to human breast cancer cells, primary tumors, and solid tumors. First, nanoparticle uptake and cell death were evaluated in three types of human breast cells: two metastatic cancerous MCF-7 and MDA-MB-231 cells and nontumorigenic MCF-10A cells. While Fl-PMNPs were not toxic to cells even at the highest concentrations used, Dox-loaded Fl-PMNPs showed significant potency, effectively killing the different breast cancer cells, albeit at different affinities. Interestingly and superior to free Dox, Dox-loaded Fl-PMNPs were found to be more effective in killing the metastatic cells (2- to 3-fold enhanced cytotoxicities for MDA-MB-231 compared to MCF-7), compared to the normal noncancerous MCF-10A cells (up to 8-fold), suggesting huge potentials as selective anticancer agents. Electron and live confocal microscopy imaging mechanistically confirmed that the nanoparticles were successfully endocytosed and packaged into vesicles inside the cytoplasm, where Dox is released and then translocated to the nucleus exerting its cytotoxic action and causing apoptotic cell death. Furthermore, commendable and enhanced penetration in 3D multilayered primary tumor cells derived from primary lesions as well as in patient breast tumor biopsies was observed, killing the tumor cells inside. The designed nanocarriers described here can potentially open new opportunities for breast cancer patients, especially in theranostic imaging and hyperthermia. While many prior studies have focused on targeting ligands to specific receptors to improve efficacies, we discovered that even with passive-targeted tailored delivery system enhanced toxic responses can be attained.

N-Acetylcysteine and metabotropic glutamate receptors: implications for the treatment of schizophrenia: a literature review.

The objective of this study is to review the available data regarding metabotropic glutamate receptors in the pathology of Schizophrenia. Further, to investigate the potential utility of N-acetylcysteine as it relates to metabotropic glutamate receptors. A PubMed based literature review was conducted using keywords related to glutamate receptors, Schizophrenia and N-acetylcysteine from June 2012 through August of 2012. Relevant cited references of selected articles were also reviewed. The knowledge base regarding glutamate receptors, both ionotropic and metabotropic is rapidly expanding. New agonists of various subsets of metabotropic glutamate receptors are available and have demonstrated potential utility in animal models. N-acetylcysteine indirectly stimulates presynaptic metabotropic glutamate receptors and has shown efficacy in two double-blind randomized controlled trials. Metabotropic glutamate receptors contribute to an understanding of glutamate dysfunction in Schizophrenia. Agents which lead to stimulation of metabotropic glutamate receptors, inclusive of N-acetylcysteine show promise as novel agents in the treatment of this disorder. An understanding of the various metabotropic glutamate receptors will be a growing necessity as agents which target them continue to emerge and enter clinical trials.

A novel SpaSA based hyper-parameter optimized FCEDN with adaptive CNN classification for skin cancer detection.

Skin cancer is the most prevalent kind of cancer in people. It is estimated that more than 1 million people get skin cancer every year in the world. The effectiveness of the disease's therapy is significantly impacted by early identification of this illness. Preprocessing is the initial detecting stage in enhancing the quality of skin images by removing undesired background noise and objects. This study aims is to compile preprocessing techniques for skin cancer imaging that are currently accessible. Researchers looking into automated skin cancer diagnosis might use this article as an excellent place to start. The fully convolutional encoder-decoder network and Sparrow search algorithm (FCEDN-SpaSA) are proposed in this study for the segmentation of dermoscopic images. The individual wolf method and the ensemble ghosting technique are integrated to generate a neighbour-based search strategy in SpaSA for stressing the correct balance between navigation and exploitation. The classification procedure is accomplished by using an adaptive CNN technique to discriminate between normal skin and malignant skin lesions suggestive of disease. Our method provides classification accuracies comparable to commonly used incremental learning techniques while using less energy, storage space, memory access, and training time (only network updates with new training samples, no network sharing). In a simulation, the segmentation performance of the proposed technique on the ISBI 2017, ISIC 2018, and PH2 datasets reached accuracies of 95.28%, 95.89%, 92.70%, and 98.78%, respectively, on the same dataset and assessed the classification performance. It is accurate 91.67% of the time. The efficiency of the suggested strategy is demonstrated through comparisons with cutting-edge methodologies.

Moringa oleifera Gum-Assisted Synthesis and Characterization of CoAgxFe2-xO4: Insight into Structural, Magnetic, Optical, and Biomedical Properties.

The sol-gel method was employed to prepare nano CoFe2O4 and silver-substituted CoFe2O4 nanohybrids (CoAgxFe2-xO4, x = 0, 0.1, 0.2, 0.3, 0.4) utilizing Moringa oleifera gum as biofuel. The morphology, size, shape, magnetic, optical, and functional groups of the crystallites were determined using various techniques such as UV-visible, Fourier transform infrared, X-ray diffraction, Rietveld, scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and photoluminescence. The produced nanoferrite has a spherical shape with cubic spinal structures. The optical properties were investigated in two different bands in the photoluminescence emission spectra at 469 and 493 nm. Saturation magnetization (Ms) and coercivity (Hc) decrease as the Ag content increases significantly. Furthermore, antibacterial (Gram-positive bacteria bacterial strains, Bacillus subtilis and Staphylococcus aureus, and Gram-negative bacterial strains, Pseudomonas aeruginosa, and Escherichia coli), antibiofilm activity (E. coli), and antioxidant (DPPH) activities were investigated. The substantial increase in the silver content offers a constructive impact on studied biomedical activities. These findings encourage additional research into the use of hybrid nanoparticles (an amalgamation of ferrite and a noble metal) in biomedical and pharmaceutical applications.

Preparation and characterization of various PVPylated divalent metal-doped ferrite nanoparticles for magnetic hyperthermia.

There is an incessant demand to keep improving on the heating responses of polymeric magnetic nanoparticles (MNPs) under magnetic excitation, particularly in the pursuit for them to be utilized for clinical hyperthermia applications. Herein, we report the fabrication of a panel of PVP-capped divalent metal-doped MFe2O4 (M ≅ Co, Ni, Zn, Mg, and Sn) MNPs prepared via the Ko-precipitation Hydrolytic Basic (KHB) methodology and assess their magneto-thermal abilities. The physiochemical, structural, morphological, compositional, and magnetic properties of the doped ferrites were fully characterized using various techniques mainly TEM, XRD, EDX, FTIR, and VSM. The obtained doped MNPs exhibited stabilized quasi-spherical sized particles (10-17 nm), pure well-crystallized cubic spinel phases, and high saturation magnetizations (Ms = 26-81 emu g-1). In response to a clinically-safe alternating magnetic field (AMF) (f = 332.8 kHz and H = 170 Oe), distinctive heating responses of these doped ferrites were attained. Hyperthermia temperatures of 42 °C can be reached very fast in only ∼5 min, with heating temperatures slowly increasing to reach up to 55 °C. The highest heating performance was observed for PVP-NiFe2O4 and the lowest for PVP-Sn-doped NPs (SAR values: PVP-NiFe2O4 > PVP-CoFe2O4 > PVP-ZnFe2O4 > PVP-MgFe2O4 > PVP-SnFe2O4). This trend was found to be directly correlated to their observed magnetic saturation and anisotropy. Heating efficiencies and specific SAR values as functions of concentration, frequency, and amplitude were also systematically investigated. Finally, cytotoxicity assay was conducted on aqueous dispersions of the doped ferrite NPs, proving their biocompatibility and safety profiles. The PVPylated metal-doped ferrite NPs prepared here, particularly Ni- and Co-doped ferrites, are promising vehicles for potential combined magnetically-triggered biomedical hyperthermia applications.