Connexin40 regulates platelet function

The presence of multiple connexins was recently demonstrated in platelets, with notable expression of Cx37. Studies with Cx37-deficient mice and connexin inhibitors established roles for hemichannels and gap junctions in platelet function. It was uncertain, however, whether Cx37 functions alone or in collaboration with other family members through heteromeric interactions in regulation of platelet function. Here we report the presence and functions of an additional platelet connexin, Cx40. Inhibition of Cx40 in human platelets or its deletion in mice reduces platelet aggregation, fibrinogen binding, granule secretion and clot retraction. The effects of the Cx37 inhibitor 37,43Gap27 on Cx40-/- mouse platelets and of the Cx40 inhibitor 40Gap27 on Cx37-/- mouse platelets revealed that each connexin is able to function independently. Inhibition or deletion of Cx40 reduces haemostatic responses in mice, indicating the physiological importance of this protein in platelets. We conclude that multiple connexins are involved in regulating platelet function, thereby contributing to haemostasis and thrombosis

Influence of different types of soils on the growth and yield of Quinoa (Chenopodium quinoa Wild.)

Quinoa is a resilient high-yielding pseudo cereal, gaining attention because of its high nutritional value, strong growth potential, and tremendous source of essential amino acids, micronutrients, vitamins, phenolic compounds, and minerals. The main aim of this investigation was to find the best suitable soil type for maximizing the growth and yield of Quinoa. The pot study was undertaken at the Department of Agronomy, Tamil Nadu Agricultural University, Coimbatore, during the Kharif 2022 season. Eight soil samples (clay loam soils of wetlands of TNAU, sandy loam soils of eastern block of TNAU, sandy loam soils of Mettupalayam, sandy clay loam soils of 36 B eastern block of TNAU, sandy clay loam soils of 37 B eastern block of TNAU, clay loam soils of Ooty, sandy clay loam soils of Govindanaickenpalayam and sandy clay loam soils of Annur) were collected round Coimbatore in Tamil Nadu and tested in a complete randomized design with three replications. The pot study results revealed that growth parameters viz. Plant height (81.5 cm), number of leaves plant-1 (164.8), leaf area (317.7 cm2), number of branches plant-1 (38.0) and dry matter production (22.78 g) were significantly higher in the clay loam soils of Ooty than all other soil types. Similarly, yield attributes such as the number of panicles plant-1 (21.7), panicle length (13.08 cm), number of grains panicle-1 (3050) and grain yield plant-1 (9.60 g) of Quinoa were also higher in the same clay loam soils followed by that in sandy clay loam soils of Govindanaickenpalayam. Red soils of Mettupalayam had shown the lowest growth, yield and yield attributes of Quinoa. Based on the above results, it was concluded that the clay loam soil of Ooty was the best suited for cultivating Quinoa crops

Development and characterisation of a novel NF-κB reporter cell line for investigation of neuroinflammation

Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation has been linked to autoimmune diseases, development and progression of cancer and neurological disorders like Alzheimer’s disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not yet been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of pro-inflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals. We used lentivirus to transduce the glioma cell line U251-MG with a tandem NF-κB reporter construct containing GFP and firefly luciferase allowing an assessment of NF-κB activity via fluorescence microscopy, flow cytometry and luminometry. We observed a robust activation of NF-κB after exposure of the reporter cell line to Tumour 2 necrosis factor alpha (TNFα) and amyloid-β peptide [1-42] as well as to LPS derived from Salmonella minnesota and Escherichia coli. Finally, we demonstrate that the U251-NF-κB-GFP-Luc reporter cells can be used for assessing the anti-inflammatory potential of pharmaceutical compounds using Bay11-7082 and IMD0354. In summary, our newly generated cell line is a robust and cost-efficient tool to study pro- and anti-inflammatory potential of drugs and biologicals in neural cells

Chloroform Extract of Rasagenthi Mezhugu, a Siddha Formulation, as an Evidence-Based Complementary and Alternative Medicine for HPV-Positive Cervical Cancers

Rasagenthi Mezhugu (RGM) is a herbomineral formulation in the Siddha system of traditional medicine and is prescribed in the southern parts of India as a remedy for all kinds of cancers. However, scientific evidence for its therapeutic efficacy in cervical cancer is lacking, and it contains heavy metals. To overcome these limitations, RGM was extracted, and the fractions were tested on HPV-positive cervical cancer cells, ME-180 and SiHa. The extracts, free from the toxic heavy metals, affected the viability of both the cells. The chloroform fraction (cRGM) induced DNA damage and apoptosis. Mitochondria-mediated apoptosis was indicated. Though both the cells responded to the treatment, ME-180 was more responsive. Thus, this study brings up scientific evidence for the efficacy of RGM against the HPV-mediated cervical cancer cells and, if the toxic heavy metals are the limitation in its use, cRGM would be a suitable candidate as evidence-based complementary and alternative medicine for HPV-positive cervical cancers

Early treatment with intranasal neostigmine reduces mortality in a mouse model of Naja naja (Indian Cobra) envenomation

Objective. Most snakebite deaths occur prior to hospital arrival; yet inexpensive, effective, and easy to administer out-of-hospital treatments do not exist. Acetylcholinesterase inhibitors can be therapeutic in neurotoxic envenomations when administered intravenously, but nasally delivered drugs could facilitate prehospital therapy for these patients. We tested the feasibility of this idea in experimentally envenomed mice. Methods. Mice received intraperitoneal injections of Naja naja venom 2.5 to 10 times the estimated LD50 and then received

Tangeretin regulates platelet function through inhibition of phosphoinositide 3-Kinase and cyclic nucleotide signaling

OBJECTIVE: Dietary flavonoids have long been appreciated in reducing cardiovascular disease risk factors, but their mechanisms of action are complex in nature. In this study, the effects of tangeretin, a dietary flavonoid, were explored on platelet function, signaling, and hemostasis. APPROACH AND RESULTS: Tangeretin inhibited agonist-induced human platelet activation in a concentration-dependent manner. It inhibited agonist-induced integrin αIIbβ3 inside-out and outside-in signaling, intracellular calcium mobilization, and granule secretion. Tangeretin also inhibited human platelet adhesion and subsequent thrombus formation on collagen-coated surfaces under arterial flow conditions in vitro and reduced hemostasis in mice. Further characterization to explore the mechanism by which tangeretin inhibits platelet function revealed distinctive effects of platelet signaling. Tangeretin was found to inhibit phosphoinositide 3-kinase-mediated signaling and increase cGMP levels in platelets, although phosphodiesterase activity was unaffected. Consistent with increased cGMP levels, tangeretin increased the phosphorylation of vasodilator-stimulated phosphoprotein at S239. CONCLUSIONS: This study provides support for the ability and mechanisms of action of dietary flavonoids to modulate platelet signaling and function, which may affect the risk of thrombotic disease

Ruthenium-conjugated chrysin analogues modulate platelet activity, thrombus formation and haemostasis with enhanced efficacy

The constant increase in cardiovascular disease rate coupled with significant drawbacks of existing therapies emphasise the necessity to improve therapeutic strategies. Natural flavonoids exert innumerable pharmacological effects in humans. Here, we demonstrate the effects of chrysin, a natural flavonoid found largely in honey and passionflower on the modulation of platelet function, haemostasis and thrombosis. Chrysin displayed significant inhibitory effects on isolated platelets, however, its activity was substantially reduced under physiological conditions. In order to increase the efficacy of chrysin, a sulfur derivative (thio-chrysin), and ruthenium-complexes (Ru-chrysin and Ru-thio-chrysin) were synthesised and their effects on the modulation of platelet function were evaluated. Indeed, Ru-thio-chrysin displayed a 4-fold greater inhibition of platelet function and thrombus formation in vitro than chrysin under physiologically relevant conditions such as in platelet-rich plasma and whole blood. Notably, Ru-thio-chrysin exhibited similar efficacy to chrysin in the modulation of haemostasis in mice. Increased bioavailability and cell permeability of Ru-thio-chrysin compared to chrysin were found to be the basis for its enhanced activity. Together, these results demonstrate that Ru-thio-coupled natural compounds such as chrysin may serve as promising templates for the development of novel anti-thrombotic agents

Exotic snakebites reported to Pennsylvania poison control centers: lessons learned on the demographics, clinical effects, and treatment of these cases

Exotic snakebites are a rare occurrence but they present a unique challenge to clinicians treating these patients. Poison control centers are often contacted to assist in the management and care of these medical emergencies. In this study, we analyzed case records of the two Pennsylvania poison control centers from 2004-2018 to describe clinical features reported as a result of exotic snakebite envenomation. For the 15-year period reviewed, 18 exotic snakebites were reported with effects ranging from mild local tissue injury to patients who were treated with mechanical ventilation due to respiratory failure. The mean age of the patients was 35 years-old and males accounted for 88% of the cases. Antivenom, the only specific treatment, was administered in seven of 18 patients within an average of four hours of envenomation. The procurement of antivenom against these exotic specific may require substantial logistical efforts due to limited stocking of this rarely used treatment. Newer, targeted, small molecule treatments that are being currently investigated may aid in the treatment of snakebites in general. However, people should be cautious when handling these exotic species and clinicians should be aware of these bites and relevant clinical effects in order to manage these when reported

Red Fox Optimizer with Data-Science-Enabled Microarray Gene Expression Classification Model

Microarray data examination is a relatively new technology that intends to determine the proper treatment for various diseases and a precise medical diagnosis by analyzing a massive number of genes in various experimental conditions. The conventional data classification techniques suffer from overfitting and the high dimensionality of gene expression data. Therefore, the feature (gene) selection approach plays a vital role in handling a high dimensionality of data. Data science concepts can be widely employed in several data classification problems, and they identify different class labels. In this aspect, we developed a novel red fox optimizer with deep-learning-enabled microarray gene expression classification (RFODL-MGEC) model. The presented RFODL-MGEC model aims to improve classification performance by selecting appropriate features. The RFODL-MGEC model uses a novel red fox optimizer (RFO)-based feature selection approach for deriving an optimal subset of features. Moreover, the RFODL-MGEC model involves a bidirectional cascaded deep neural network (BCDNN) for data classification. The parameters involved in the BCDNN technique were tuned using the chaos game optimization (CGO) algorithm. Comprehensive experiments on benchmark datasets indicated that the RFODL-MGEC model accomplished superior results for subtype classifications. Therefore, the RFODL-MGEC model was found to be effective for the identification of various classes for high-dimensional and small-scale microarray data