Comparative analysis of parametric B-spline and Hermite cubic spline based methods for accurate ECG signal modeling.

Analyzing Electrocardiogram (ECG) signals is imperative for diagnosing cardiovascular diseases. However, evaluating ECG analysis techniques faces challenges due to noise and artifacts in actual signals. Machine learning for automatic diagnosis encounters data acquisition hurdles due to medical data privacy constraints. Addressing these issues, ECG modeling assumes a crucial role in biomedical and parametric spline-based methods have garnered significant attention for their ability to accurately represent the complex temporal dynamics of ECG signals. This study conducts a comparative analysis of two parametric spline-based methods-B-spline and Hermite cubic spline-for ECG modeling, aiming to identify the most effective approach for accurate and reliable ECG representation. The Hermite cubic spline serves as one of the most effective interpolation methods, while B-spline is an approximation method. The comparative analysis includes both qualitative and quantitative evaluations. Qualitative assessment involves visually inspecting the generated spline-based models, comparing their resemblance to the original ECG signals, and employing power spectrum analysis. Quantitative analysis incorporates metrics such as root mean square error (RMSE), Percentage Root Mean Square Difference (PRD) and cross correlation, offering a more objective measure of the model's performance. Preliminary results indicate promising capabilities for both spline-based methods in representing ECG signals. However, the analysis unveils specific strengths and weaknesses for each method. The B-spline method offers greater flexibility and smoothness, while the cubic spline method demonstrates superior waveform capturing abilities with the preservation of control points, a critical aspect in the medical field. Presented research provides valuable insights for researchers and practitioners in selecting the most appropriate method for their specific ECG modeling requirements. Adjustments to control points and parameterization enable the generation of diverse ECG waveforms, enhancing the versatility of this modeling technique. This approach has the potential to extend its utility to other medical signals, presenting a promising avenue for advancing biomedical research.

Exploring a new frontier in cardiac diagnosis: ECG analysis enhanced by machine learning and parametric quartic spline modeling.

The heart's study holds paramount importance in human physiology, driving valuable research in cardiovascular health. However, assessing Electrocardiogram (ECG) analysis techniques poses challenges due to noise and artifacts in authentic recordings. The advent of machine learning systems for automated diagnosis has heightened the demand for extensive data, yet accessing medical data is hindered by privacy concerns. Consequently, generating artificial ECG signals faithful to real ones is a formidable task in biomedical signal processing. This paper introduces a method for ECG signal modeling using parametric quartic splines and generating a new dataset based on the modeled signals. Additionally, it explores ECG classification using three machine learning techniques facilitated by Orange software, addressing both normal and abnormal sinus rhythms. The classification enables early detection and prediction of heart-related ailments, facilitating timely clinical interventions and improving patient outcomes. The assessment of synthetic signal quality is conducted through power spectrum analysis and cross-correlation analysis, power spectrum analysis of both real and synthetic ECG waves provides a quantitative assessment of their frequency content, aiding in the validation and evaluation of synthetic ECG signal generation techniques. Cross-correlation analysis revealing a robust correlation coefficient of 0.974 and precise alignment with a negligible time lag of 0.000 s between the synthetic and real ECG signals. Overall, the adoption of quartic spline interpolation in ECG modeling enhances the precision, smoothness, and fidelity of signal representation, thereby improving the effectiveness of diagnostic and analytical tasks in cardiology. Three prominent machine learning algorithms, namely Decision Tree, Logistic Regression, and Gradient Boosting, effectively classify the modeled ECG signals with classification accuracies of 0.98620, 0.98965, and 0.99137, respectively. Notably, all models exhibit robust performance, characterized by high AUC values and classification accuracy. While Gradient Boosting and Logistic Regression demonstrate marginally superior performance compared to the Decision Tree model across most metrics, all models showcase commendable efficacy in ECG signal classification. The study underscores the significance of accurate ECG modeling in health sciences and biomedical technology, offering enhanced accuracy and flexibility for improved cardiovascular health understanding and diagnostic tools.

Chain length effect of spiro-ring N-alkylation on photophysical signalling parameters in Fe(III) selective rhodamine probes.

Manifestation of photophysical signalling parameters in rhodamine derivatives exhibiting complexation induced spiro-ring opening is crucial for the realization of selective metal ion detection at trace levels. Substitution of various functional groups, such as alkylation to the core architecture, modulates the physico-chemical properties of such molecular probes. Despite a few studies, relationships between the extent of photophysical signal modulations and the chain lengths of n-alkyl substituents are still elusive. In this investigation, a few molecular probes based on the rhodamine B (1-5) and rhodamine 6G (6-10) platform were synthesized by their derivatization with n-alkyl substituents of varying chain lengths at the amino-donor of their spiro-ring end, which exhibited Fe(III)-selective absorption and fluorescence 'off-on' signal transduction along with colorization of solution. The Fe(III)-selectivity in these probes remained the same despite their structural distinctions through varied n-alkyl chain lengths of the substituents; however, the quantifiable signalling parameters such as spectroscopic enhancement factors, sensitivity, the kinetics of spiro-ring opening and effectiveness of probe-Fe(III) interactions were analyzed. These parameters were also correlated in terms of the influence of different chain lengths of n-alkyl substituents that efficiently contributed to their inter-componential interactive stereo-electronic environment.

A rapid method for solubilization of chimeric human interferon regulatory factor-1 (IRF-1) protein in Escherichia coli.

Interferon regulatory factor-1 (IRF-1) is a vertebrate transcription factor that plays significant roles in cell cycle regulation, anti-viral response, tumor suppression and immune response. High-level expression of recombinant IRF-1 at 37 °C leads to the formation of insoluble aggregates (insoluble fraction) in Escherichia coli (E. coli), which usually devoid of biological activity. In this study, we use chemical additives such as mannitol, proline, L-arginine and CTAB (cetyl trimethly ammonium bromide) at the recommended concentration during cell lysis to aid in solubility at 37 °C. The use of additives resulted in the increased solubility of the recombinant glutathione S-transferase-linked human IRF-1, with L-arginine being most effective. Here, we developed an efficient process for the manufacturing of soluble IRF-1 with the aid of minimizing the formation of degradation products and optimizing protein purification conditions. This result was further confirmed by western blot with anti-GST and anti-IRF-1 polyclonal antibodies. The functionality of GST-huIRF-1 was attained by elerophoretic mobility shift assay study as a clear band shifting showed with virus response element-Interferon beta (VRE-IFNß) promoter region. Taken together, the biological activity of purified GST-huIRF-1 was also optimized and confirmed by supershift assay concluded that GST-huIRF-1 interacts with the VRE motif of IFNß promoter that reflected to require for IFNß gene regulation. We describe a straightforward approach for the production of absolutely soluble and biologically active IRF-1 in E. coli. This method can be further used for the study of other recombinant proteins and this study will pave way for the analysis of IRF-1 function in vitro.

Effect of n-alkyl substitution on Cu(ii)-selective chemosensing of rhodamine B derivatives.

Rhodamine B hydrazide-based molecular probes (1-10) were synthesized by derivatization with n-alkyl chains of different lengths at the hydrazide amino end. These probes exhibited selective absorption (A∼557) and fluorescence (I∼580) 'off-on' signal transduction along with a colourless → magenta colour transition in the presence of Cu(ii) ions among all the competitive metal ions investigated. The effective coordination of these probes to Cu(ii) ions under the investigated environment forming [Cu·L]2+ (L = 1-5) and [Cu·L2]2+ (L = 6-10) complexes led to their spiro-ring opening, which in turn was expressed through signatory spectral peaks of ring-opened rhodamine. All these probes exhibited Cu(ii) selectivity in signalling despite structural modifications to the core receptor unit through variation of the nature of the alkyl substituents. However, the sensitivity of the signalling and kinetics of the spiro-ring opening varied and could be correlated with the number of carbon atoms present in the n-alkyl substituents. Structural elucidation with X-ray diffraction and X-ray photoemission spectroscopic analyses provided further insight into the structure-function correlation in their Cu(ii) complexes. These probes with Cu(ii) coordination showed selectivity in signalling, high complexation affinity (log Ka = 4.8-8.8), high sensitivity (LOD = 4.1-80 nM), fast response time (rate = 0.0017-0.0159 s-1) and reversibility with counter anions, which ascertained their potential utility as chemosensors for Cu(ii) ion detection.

Reduced-sodium cheeses: Implications of reducing sodium chloride on cheese quality and safety.

Sodium chloride (NaCl) universally well-known as table salt is an ancient food additive, which is broadly used to increase the storage stability and the palatability of foods. Though, in recent decades, use of table salt in foods is a major concern among the health agencies of the world owing to ill effects of sodium (Na) that are mostly linked to hypertension and cardiovascular diseases. As a result, food scientists are working to decrease the sodium content in food either by decreasing the rate of NaCl addition or by partial or full replacement of NaCl with other suitable salts like potassium chloride (KCl), calcium chloride (CaCl2 ), or magnesium chloride (MgCl2 ). However, in cheese, salt reduction is difficult to accomplish owing to its multifaceted role in cheese making. Considering the significant contribution in dietary salt intake (DSI) from cheese, researchers across the globe are exploring various technical interventions to develop reduced-sodium cheeses (RSCs) without jeopardizing the quality and safety of cheeses. Thus, the purpose of this study is to provide an insight of NaCl reduction on sensory, physicochemical, and technofunctional attributes of RSCs with an aim to explore various strategies for salt reduction without affecting the cheese quality and safety. The relationship between salt reduction and survival of pathogenic and spoilage-causing microorganisms and growth of RSCs microflora is also discussed. Based on the understanding of conceptual and applied information on the complex changes that occur in the development of RSCs, the quality and safety of RSCs can be accomplished effectively in order to reduce the DSI from cheese.

Brain natriuretic peptide (BNP) expressing sensory neurons are not involved in acute, inflammatory or neuropathic pain.

Background: We recently demonstrated that brain natriuretic peptide is expressed in the dorsal root ganglia, and that brain natriuretic peptide is required for normal detection of pruritogens. We further showed that the receptor for brain natriuretic peptide, natriuretic peptide receptor A, is present in the spinal cord, and elimination of these neurons profoundly attenuates scratching to itch-inducing compounds. However, the potential modulatory roles of brain natriuretic peptide in nociception, inflammation, and neuropathic mechanisms underlying the sensation of pain have not been investigated in detail. Findings: To demonstrate the involvement of brain natriuretic peptide in pain, we compared the behavioral responses of brain natriuretic peptide knockout mice with their wild-type littermates. First, we showed that brain natriuretic peptide is not required in chemically induced pain responses evoked by the administration of capsaicin, allyl isothiocyanate, adenosine 5'-triphosphate, or inflammatory soup. We further measured pain behaviors and found no involvement of brain natriuretic peptide in hot, cold, or mechanical nociceptive responses in mice, nor did we find evidence for the involvement of brain natriuretic peptide in neuroinflammatory sensitization elicited by complete Freund's adjuvant or in neuropathic pain. Conclusions: These results demonstrate that brain natriuretic peptide is not essential for pain-related behaviors.

Oral administration of veratric acid, a constituent of vegetables and fruits, prevents cardiovascular remodelling in hypertensive rats: a functional evaluation.

In our previous studies, veratric acid (VA) shows beneficial effect on hypertension and its associated dyslipidaemia. In continuation, this study was designed to investigate the effect of VA, one of the major benzoic acid derivatives from vegetables and fruits, on cardiovascular remodelling in hypertensive rats, primarily assessed by functional studies using Langendorff isolated heart system and organ bath system. Hypertension was induced in male albino Wistar rats by oral administration of N ω -nitro-l-arginine methyl ester hydrochloride (l-NAME) (40 mg/kg body weight (b.w.)) in drinking water for 4 weeks. VA was orally administered at a dose of 40 mg/kg b.w. l-NAME-treated rats showed impaired cardiac ventricular and vascular function, evaluated by Langendorff isolated heart system and organ bath studies, respectively; a significant increase in the lipid peroxidation products such as thiobarbituric acid-reactive substances and lipid hydroperoxides in aorta; and a significant decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase and levels of GSH, vitamin C and vitamin E in aorta. Fibrotic remodelling of the aorta and heart were assessed by Masson's Trichrome staining and Van Gieson's staining, respectively. In addition, l-NAME rats showed increased heart fibronectin expression assessed by immunohistochemical analysis. VA supplementation throughout the experimental period significantly normalised cardiovascular function, oxidative stress, antioxidant status and fibrotic remodelling of tissues. These results of the present study conclude that VA acts as a protective agent against hypertension-associated cardiovascular remodelling.

Protective effect of alcoholic extract of stem of Entada pursaetha in dextran sulphate sodium-induced colitis in mice.

Oxidative stress has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). Entada pursaetha has been demonstrated to have antioxidant and anti-inflammatory effects. In this study, we investigated the effects of stem of alcoholic extract of E. pursaetha (PSE) in dextran sodium sulfate (DSS)-induced colitis in mice. The protective effect of PSE was determined at three different doses of 30, 100 and 300 mg/kg body weight by oral gavage for 7 days. Morphological (colon length and colon weight/length ratio), clinical (disease activity index) and macroscopic (damage score) features were determined using standard criteria. Lipid peroxides (determined as malonaldehyde; MDA), enzymatic (superoxide dismutase; SOD and catalase; CAT) and non- enzymatic antioxidants (reduced glutathione; GSH), nitrate and nitrite (NOx) levels and myeloperoxidase (PO) activity in colon tissues were determined. The DSS damaged the colonic tissue, increased MPO activity, lipid peroxidation and NOx levels, reduced the antioxidant enzymes and glutathione and lowered the body weight. PSE significantly reduced the inflammation of colon and reversed the increase in MPO activity induced by DSS. It also significantly increased the SOD and catalase activities and did not elicit any effect on depleted levels of GSH in the colonic tissue. In addition, PSE also significantly decreased colonic NOx and MDA levels compared to DSS-treated mice; reduced both infiltration of inflammatory cells and the mucosal damage in colon on histopathological examination. The results suggested the protective potential of PSE in DSS-induced colitis and this might be attributed to its anti-inflammatory and antioxidant activities.

Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats.

Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100ppm) through drinking water for 90 consecutive days. Atorvastatin (10mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis.

Atorvastatin restores arsenic-induced vascular dysfunction in rats: modulation of nitric oxide signaling and inflammatory mediators.

We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100ppm) through drinking water for 90 consecutive days. Atorvastatin (10mg/kg bw, orally) was administered once daily during the last 30days of arsenic exposure. On the 91(st) day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited Emax of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1ß, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules.

A virus inhibitory protein isolated from Cyamopsis tetragonoloba (L.) Taub. upon induction of systemic antiviral resistance shares partial amino acid sequence homology with a lectin.

KEY MESSAGE: Two virus inhibitory proteins were purified from Cyamopsis tetragonoloba , induced to resist virus infections by CIP-29, a systemic resistance inducing protein from Clerodendrum inerme, and characterized. One of them shared homology with a lectin. CIP-29, a known 29 kDa systemic antiviral resistance inducing protein isolated from Clerodendrum inerme, has been used to induce systemic resistance in Cyamopsis tetragonoloba against Sunn-hemp rosette virus (SRV). Paper reports the detection of virus inhibitory activity in induced-resistant leaf sap of C. tetragonoloba, and the purification of two virus inhibitory agents (VIAs) thereof. VIA activity was recorded as a reduction in lesion number of SRV, Tobacco mosaic virus, and Papaya ringspot virus, when they were incubated separately with resistant sap and inoculated onto susceptible C. tetragonoloba, Nicotiana tabacum cv. Xanthi-nc, and Chenopodium quinoa, respectively. The two VIAs were isolated from resistant C. tetragonoloba plant leaves using combinations of column chromatography. Both were basic proteins, and since their M r was 32 and 62 kDa, these VIAs were called CT-VIA-32 and CT-VIA-62, respectively, on the basis of their molecular mass and the host. CT-VIA-62 displayed better activity, and was thus studied further. It tested positive for a glycoprotein, and was serologically detected only in leaf tissue post-induction. Tryptic peptides generated in-gel, post SDS-PAGE of CT-VIA-62, were sequenced through LC/MS/MS. All CT-VIA-62 peptides were found to share homologies with proteins from Medicago truncatula that possess a mannose-binding lectin domain.

Protective effect of alcoholic extract of Entada pursaetha DC. against CCl4-induced hepatotoxicity in rats.

The alcoholic extract of stem of E. pursaetha (PSE, 30, 100, 300 mg/kg body weight, po for 7 days) showed hepatoprotective activity against CCl4 (2 mL/kg body weight, ip)-induced hepatotoxicity. The extract exhibited a significant dose-dependent hepatoprotective effect comparable to standard drug silymarin, by preventing increase in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total protein, and total bilirubin, lactate dehydrogenase; by lowering hepatic levels of malonaldehyde, nitrate-nitrite, myeloperoxidase activity; enhancing activities of antioxidant enzymes, superoxide dismutase, catalase and increasing reduced glutathione levels in liver, which suggests the antioxidant property of PSE. Histopathological studies also supported the above biochemical parameters. The results suggested that alcoholic extract of E. pursaetha possesses significant hepatoprotective activity in CCl4-induced acute hepatotoxicity in rats and this is likely to be mediated through its antioxidant activities.

Glucoconjugated Dinuclear Copper(II) Complex: An Efficient Catalyst for Stereoselective Synthesis of Trisubstituted Propargylamines via Solvent-free A3 Coupling Reaction.

Development of catalytic systems using nontoxic natural precursors is the need of the era, and along this line, we have synthesized a new D-glucose derived ligand (4,6-O-ethylidene-N-(2-hydroxy-4-(octyloxy)benzylidene)-ß-D-glucopyranosylamine) and its dinuclear copper(II) complex. The molecular structure of the complex has been established by single-crystal X-ray diffraction studies and detailed noncovalent intermolecular interactions present in it has been explored by Hirshfeld surface analysis. Further, the complex has been used as catalyst in the enantioselective (87-99% ee) synthesis of propargylamines in good to excellent yield (82-95%) via aldehyde-amines-alkynes (A3) coupling reaction under solvent-free condition. The formation of aminal intermediate during the reaction has been confirmed by 1H-NMR and single-crystal X-ray diffraction studies. The catalytic system is reusable without any appreciable loss in the enantioselectivity or product yield.

TRPV4 channel activation leads to endothelium-dependent relaxation mediated by nitric oxide and endothelium-derived hyperpolarizing factor in rat pulmonary artery.

The purpose of the present study was to characterize TRPV4 channels in the rat pulmonary artery and examine their role in endothelium-dependent relaxation. Tension, Real-Time polymerase chain reaction (Real-Time PCR) and Western blot experiments were conducted on left and right branches of the main pulmonary artery from male Wistar rats. TRPV4 channel agonist GSK1016790A (GSK) caused concentration-related robust relaxation (Emax 88.6±5.5%; pD2 8.7±0.2) of the endothelium-intact pulmonary artery. Endothelium-denudation nearly abolished the relaxation (Emax 5.6±1.3%) to GSK. TRPV4 channel selective antagonist HC067047 significantly attenuated GSK-induced relaxation (Emax 56.2±6.6% vs. control Emax 87.9±3.3%) in endothelium-intact vessels, but had no effect on either ACh-induced endothelium-dependent or SNP-induced endothelium-independent relaxations. GSK-induced relaxations were markedly inhibited either in the presence of NO synthase inhibitor L-NAME (Emax 8.5±2.7%) or sGC inhibitor ODQ (Emax 28.1±5.9%). A significant portion (Emax 30.2±4.4%) of endothelium-dependent relaxation still persisted in the combined presence of L-NAME and cyclooxygenase inhibitor indomethacin. This EDHF-mediated relaxation was sensitive to inhibition by 60mM K(+) depolarizing solution or K(+) channel blockers apamin (SKCa; KCa2.3) and TRAM-34 (IKCa; KCa3.1). GSK (10(-10)-10(-7)M) caused either modest decrease or increase in the basal tone of endothelium-intact or denuded rings, respectively. We found a greater abundance (>1.5 fold) of TRPV4 mRNA and protein expressions in endothelium-intact vs. denuded vessels, suggesting the presence of this channel in pulmonary endothelial and smooth muscle cells as well. The present study demonstrated that NO and EDHF significantly contributed to TRPV4 channel-mediated endothelium-dependent relaxation of the rat pulmonary artery.

Phage for drug delivery vehicles.

Viruses being the natural carriers of gene have been widely used as drug delivery systems. However, the commonly used eukaryotic viruses such as adenoviruses, retroviruses, and lentiviruses, besides efficiently targeting the cells, can also stimulate immunological response or disrupt tumour suppressor genes leading to cancer. Consequently, there has been an increase interest in the scientific fraternity towards exploring other alternatives, which are safer and equally efficient for drug delivery. Bacteriophages, in this context have been at the forefront as an efficient, reliable, and safer choice. Novel phage dependent technologies led the foundation of peptide libraries and provides way to recognising abilities and targeting of specific ligands. Hybridisation of phage with inorganic complexes could be an appropriate strategy for the construction of carrying bioinorganic carriers. In this chapter, we have tried to cover major advances in the phage species that can be used as drug delivery vehicles.

Current status and applications of genus Geobacillus in the production of industrially important products-a review.

The genus Geobacillus is one of the most important genera which mainly comprises gram-positive thermophilic bacterial strains including obligate aerobes, denitrifiers and facultative anaerobes having capability of endospore formation as well. The genus Geobacillus is widely distributed in nature and mostly abundant in extreme locations such as cool soils, hot springs, hydrothermal vents, marine trenches, hay composts and dairy plants. Due to plasticity towards environmental adaptation, the Geobacillus sp. shows remarkable genome diversification and acquired many beneficial properties, which facilitates their exploitation for many biotechnological applications. Many thermophiles are of biotechnological importance and having considerable interest in commercial applications for the production of industrially important products. Recently, due to catabolic versatility especially in the degradation of hemicellulose and starch containing agricultural waste and rapid growth rates, these microorganisms show potential for the production of biofuels, thermostable enzymes and bioremediation. This review mainly summarizes the status of Geobacillus sp. including its notable properties, biotechnological studies and its potential application in the production of industrially important products.

Development and evaluation of mucoadhesive buccal patches of flurbiprofen.

In the present study, an attempt was made to formulate mucoadhesive buccal patches of flurbiprofen (FBN) in order to enhance solubility. Solubity enhancement was attempted by making solid dispersion of drug with beta-CD (cyclodextrin). Initially preformulation were carried out using reported methods. Buccal patches were prepared by solvent casting technique using polymers like polyvinyl alcohol (PVA), sodium carboxymethyl cellulose (SCMC), and hydroxypropyl methylcellulose (HPMC). The prepared patches were evaluated for their weight variation, thickness, folding endurance, surface pH, swelling index, in vitro residence time, in vitro permeation studies, drug content uniformity and bioadhesion test.

Role of TRP Channels in Shaping the Gut Microbiome.

Transient receptor potential (TRP) channel family proteins are sensors for pain, which sense a variety of thermal and noxious chemicals. Sensory neurons innervating the gut abundantly express TRPA1 and TRPV1 channels and are in close proximity of gut microbes. Emerging evidence indicates a bi-directional gut-brain cross-talk in several entero-neuronal pathologies; however, the direct evidence of TRP channels interacting with gut microbial populations is lacking. Herein, we examine whether and how the knockout (KO) of TRPA1 and TRPV1 channels individually or combined TRPA1/V1 double-knockout (dKO) impacts the gut microbiome in mice. We detect distinct microbiome clusters among the three KO mouse models versus wild-type (WT) mice. All three TRP-KO models have reduced microbial diversity, harbor higher abundance of Bacteroidetes, and a reduced proportion of Firmicutes. Specifically distinct arrays in the KO models are determined mainly by S24-7, Bacteroidaceae, Clostridiales, Prevotellaceae, Helicobacteriaceae, Rikenellaceae, and Ruminococcaceae. A1KO mice have lower Prevotella, Desulfovibrio, Bacteroides, Helicobacter and higher Rikenellaceae and Tenericutes; V1KO mice demonstrate higher Ruminococcaceae, Lachnospiraceae, Ruminococcus, Desulfovibrio and Mucispirillum; and A1V1dKO mice exhibit higher Bacteroidetes, Bacteroides and S24-7 and lower Firmicutes, Ruminococcaceae, Oscillospira, Lactobacillus and Sutterella abundance. Furthermore, the abundance of taxa involved in biosynthesis of lipids and primary and secondary bile acids is higher while that of fatty acid biosynthesis-associated taxa is lower in all KO groups. To our knowledge, this is the first study demonstrating distinct gut microbiome signatures in TRPA1, V1 and dKO models and should facilitate prospective studies exploring novel diagnostic/ therapeutic modalities regarding the pathophysiology of TRP channel proteins.

Atorvastatin restores the impaired vascular endothelium-dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis.

Sepsis has been reported to impair endothelium-dependent vasodilations mediated by nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Although some studies demonstrate that statins can improve NO-mediated response in septic animals, little is known about its effect on the EDHF response. The present study examined the effects of atorvastatin pretreatment on sepsis-induced endothelial dysfunctions and hypotension in rats. Eighteen hours after the induction of sepsis by cecal ligation and puncture, thoracic aorta and second generation pulmonary arteries were isolated to examine acetylcholine-induced endothelium-dependent dilations mediated by NO and EDHF, respectively. The messenger RNA (mRNA) expression for endothelial NO synthase (eNOS) and inducible NO synthase (iNOS) was done by real-time polymerase chain reaction. NO was measured as nitrate/nitrite release using Griess method. Mean arterial pressure was measured by the invasive method. Sepsis significantly decreased (26%) the relaxation response to acetylcholine in the rat aorta. It also markedly inhibited the eNOS mRNA expression and acetylcholine-stimulated NO release in this vessel. Pretreatment of the rats with atorvastatin (10 mg/kg, orally) 48, 24, and 2 hours before induction of sepsis preserved acetylcholine-induced relaxation, eNOS mRNA expression, acetylcholine-stimulated NO release, and attenuated increase in the inducible NO synthase mRNA expression and basal NO production in the aorta. The maximal EDHF response mediated by acetylcholine was 25.30% +/- 3.00% in the pulmonary artery. Sepsis abolished this response but atorvastatin restored it (22.55% +/- 2.50%). Atorvastatin, however, failed to prevent sepsis-induced hypotension. These results suggest that atorvastatin can restore impaired endothelium-dependent vasodilations mediated by NO and EDHF but not hypotension in sepsis.