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Curcumin, a major bioactive component of turmeric (Curcuma longa), is known for its multiple health benefits. Curcumin as such is a mixture of its analogs: bisdemethoxycurcumin (BDMC)-3%, and demethoxycurcumin (DMC)-17%. Although the effect of curcumin on platelets is documented, the effect of BDMC and DMC on platelets is less studied. Considering the indispensable role played by platelets in hemostasis, thrombosis, inflammation, and immunity, the present study evaluates the effect of curcumin, DMC and BDMC on platelet apoptosis. The components of curcumin were purified by silica-gel column chromatography. The purity and mass analysis of the purified curcuminoids was determined by RP-HPLC and LC-MS respectively. When analyzed for platelet apoptotic markers, only BDMC demonstrated increased incidence of platelet apoptotic markers including increase in intracellular Ca2+, decrease in ∆ψm, alteration in BCl-2 family proteins, the release of cytochrome c, caspase activation, and PS externalization via activation of ERK activation. ERK inhibitor PD98059 significantly alleviated BDMC induced decrease in ∆ψm, alteration in BCl-2, caspase-8 activation and PS externalization. Our results demonstrate that curcumin, DMC and BDMC differentially act on platelet in inducing apoptosis and the study highlights that the toxicity associated with curcumin therapy might be attributed to BDMC in the mammalian system.

Leishmaniasis is an endemic parasitic disease, predominantly found in the poor locality of Africa, Asia and Latin America. It is associated with malnutrition, weak immune system of people and their housing locality. At present, it is diagnosed by microscopic identification, molecular and biochemical characterisation or serum analysis for parasitic compounds. In this study, we present a new approach for diagnosing Leishmaniasis using cognitive computing. The Genetic datasets of leishmaniasis are collected from Gene Expression Omnibus database and it’s then processed. The algorithm for training and developing a model, based on the data is prepared and coded using python. The algorithm and their corresponding datasets are integrated using TensorFlow dataframe. A feed forward Artificial Neural Network trained model with multi-layer perceptron is developed as a diagnosing model for Leishmaniasis, using genetic dataset. It is developed using recurrent neural network. The cognitive model of the trained network is interpreted using the maps and mathematical formula of the influencing parameters. The credit of the system is measured using the accuracy, loss and error of the system. This integrated system of the leishmaniasis genetic dataset and neural network proved to be the good choice for diagnosis with higher accuracy and lower error. Through this approach, all records of the data are effectively incorporated into the system. The experimental results of feed forward multilayer perceptron model after normalization; mean square error (219.84), loss function (1.94) and accuracy (85.71%) of the model, shows good fit of model with the process and it could possibly serve as a better solution for diagnosing Leishmaniasis in future, using genetic datasets.The code is available in Github repository:https://github.com/shailzasingh/Machine-Learning-code-for-analyzing-genetic-dataset-in-Leishmaniasis

In the past decade, arboviruses - arthropod-borne viruses - have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus (CHIKV), an arbovirus that belongs to the alphavirus genus, is a re-emerging arthritogenic virus that has caused explosive outbreaks since 2006, notably in the Reunion Island, and more recently in the Caribbean, South America, India and South-East Asia. The severity of arthritic disease caused by CHIKV has prompted public health authorities of affected countries to develop specific guidelines to tackle this pathogen. CHIKV disease (CHIKVD) manifests first as an acute stage of severe joint inflammation and febrile illness, which later progresses to a chronic stage, where patients can experience debilitating and persisting articular pain for extended periods. This review aims to provide a broad perspective on current knowledge of CHIKV pathogenesis by identifying key clinical and experimental studies that have contributed to our understanding of CHIKVD to date. In addition, this review explores the practical aspects treatment and management of both acute and chronic CHIKVD patients based on clinical experience during CHIKV outbreaks. Finally, recent findings on potential therapeutic solutions - from antivirals to immunomodulatory drugs - are reviewed to provide both viral immunologists and clinical rheumatologists with a balanced perspective on the nature of a re-emerging arboviral disease of significant public health concern, and an insight into future therapeutic approaches to better address the treatment and management of CHIKVD patients.

Oxidative stress-induced methemoglobinemia remained an untouched area in venom pharmacology till date. This study for the first time explored the potential of animal venoms to oxidize hemoglobin to methemoglobin. In in vitro whole-blood assay, methemoglobin forming ability of venoms varied as Naja naja > Ophiophagus hannah > Echis carinatus > Daboia russellii > Apis mellifera > Mesobuthus tamulus > Hippasa partita. Being highly potential, N. naja venom was further studied to observe methemoglobin formation in RBCs and in combinations with PMNs and PBMCs, where maximum effect was observed in RBCs + PMNs combination. Naja naja venom/externally added methemoglobin-induced methemoglobin formation was in parallel with ROS generation in whole blood/RBCs/RBCs + PMNs/RBCs + PBMCs. In in vivo studies, the lethal dose (1 mg/kg body weight, i.p.) of N. naja venom readily induced methemoglobin formation, ROS generation, expression of inflammatory markers, and hypoxia-inducible factor-3α. Although the mice administered with three effective doses of antivenom recorded zero mortality; the methemoglobin and ROS levels remained high. However, one effective dose of antivenom when administered along with melatonin (1:50; venom/melatonin, w/w), not only offered 100% survival of experimental mice, but also significantly reduced methemoglobin level, and oxidative stress markers including hypoxia-inducible factor-3α. This study provides strong drive that, complementing melatonin would not only reduce the antivenom load, but for sure greatly increase the success rate of antivenom therapy and drastically minimize the global incidence of snakebite deaths. However, further detailed investigations are needed before translating the combined therapy towards the bed side.

Highly stretchable and highly resilient polymer-clay nanocomposite hydrogels were synthesized by in situ polymerization of acrylamide in the presence of pristine montmorillonite (MMT) or chitosan-treated MMT nanoplatelets at an elevated temperature. Both nanocomposite hydrogels can be stretched to a strain of no less than 1290%. The treatment of clay with chitosan improves the tensile strength, elongation at break, and energy at break of the nanocomposite hydrogel by 237%, 102%, and 389%, respectively, due to the strong chitosan-MMT electrostatic interaction and the grafting of polyacrylamide onto chitosan chains. Both hydrogels display excellent resilience with low hysteresis; with a maximum tensile strain of 50%, ultralow hysteresis is found, while, with a maximum strain of 500%, both hydrogels fully recover their original state in just 1 min. The superb resilience of the nanocomposite hydrogels is attributed to the strong interactions within the hydrogels brought by chain branching, multiple hydrogen bonding, covalent bonding, and/or electrostatic force. The hydrogels can be fabricated into different shapes and forms, including microfibers spun using pressurized gyration, which may find a variety of potential applications in particular in healthcare.

Chronic hyperglycemia is one of the characteristic conditions associated with Diabetes Mellitus (DM), which often exerts deleterious effects on erythrocyte morphology and hemodynamic properties leading to anemia and diabetes-associated vascular complications. High glucose-induced over production of reactive oxygen species (ROS) can alter the blood cell metabolism and biochemical functions subsequently causing eryptosis (red blood cell death), yet another complication of concern in DM. Therefore, blocking high glucose-induced oxidative damage and subsequent eryptosis is of high importance in the better management of DM and associated vascular complications. In this study, we synthesized an oxolane derivative 1-(2,2-dimethyltetrahydrofuro[2,3][1,3]dioxol-5-yl)ethane-1,2-diol (DMTD), and demonstrated its efficacy to mitigate hyperglycemia-induced ROS generation and subsequent eryptosis. We showed that DMTD effectively inhibits high glucose-induced ROS generation, intracellular calcium levels, phosphaditylserine (PS) scrambling, calpain and band 3 activation, LDH leakage, protein glycation and lipid peroxidation, meanwhile enhances the antioxidant indices, osmotic fragility and Na+/K+-ATPase activity in erythrocytes. DMTD dose dependently decreased the glycated hemoglobin level and enhances the glucose utilization by erythrocytes in vitro. Further, DMTD alleviated the increase in ROS production, intracellular Ca2 + level and PS externalization in the erythrocytes of human diabetic subjects and enhanced the Na+/K+-ATPase activity. Taken together, the synthesized oxolane derivative DMTD could be a novel synthetic inhibitor of high glucose-induced oxidative stress and eryptosis. Considering the present results DMTD could be a potential therapeutic to treat DM and associated complications and open new avenues in developing synthetic therapeutic targeting of DM-associated complications.

Based on a case study of India's downstream hydrocarbon regulator, this article argues that the success or failure of independent regulation in industries supplying basic goods and services is determined by the politico-economic context in which the regulator functions. In a developing country with a large number of poor people without access to basic necessities such as water, energy, or roads, independent economic regulation by itself can deliver little, unless backed by a strong political will.

Recent studies have reported the platelet proapoptotic propensity of plant-derived molecules such as, resveratrol, thymoquinone, andrographolide and gossypol. Meanwhile, there were also reports of phytochemicals such as cinnamtannin B1, which shows antiapoptotic effect towards platelets. Platelets are mainly involved in hemostasis, thrombosis and wound healing. However, altered platelet functions can have serious pathological outcomes that include cardiovascular diseases. Platelets are sensitive to external and internal stimuli including therapeutic and dietary components. The anuclear platelets do undergo apoptosis via mitochondrial pathway. However, exaggerated rate of platelet apoptosis could lead to thrombocytopenia and other bleeding disorders. The present study deals with ameliorative efficacy of crocin on sesamol-induced platelet apoptosis. The antiapoptotic property of crocin and the proapoptotic tendency of sesamol in platelets were previously demonstrated. Therefore, it was interesting to see how these two compounds would interact and wield their effects on human platelets. Crocin effectively inhibited sesamol-induced oxidative stress on platelets, which was evidenced by the measurement of endogenously generated reactive oxygen species, particularly hydrogen peroxide, and changes in thiol levels. Further, crocin abrogated sesamol-induced biochemical events of apoptosis in platelets, which include intracellular calcium mobilization, changes in mitochondrial membrane integrity, cytochrome c release, caspase activity and phosphatidylserine externalization. Even though sesamol has proapoptotic effects on platelets, its anti-platelet activity cannot be neglected. Thus, the study proposes that sesamol could be supplemented with crocin, an approach that could not only abolish the toxic effects of sesamol on platelets, but also enhance the quality of treatment due to their synergistic action.

Background Arthritis is a common degenerative joint disease characterized by deterioration of articular cartilage, subchondral bone, and associated with immobility, pain and inflammation. The incessant action of reactive oxygen species (ROS) during progressive arthritis causes severe oxidative damage to vital organs and circulatory system. Purpose In this study we investigated the ability of guggulipid (GL), a lipid rich extract from the gum resin of the plant Commiphora whighitii to suppress the progressive arthritis and associated liver oxidative stress both in vivo and in vitro. Study design/Methods The anti-arthritic ability of GL was demonstrated in vitro using IL-1β stimulated bovine nasal cartilage model and in vivo Freund's complete adjuvant-induced arthritic rat model. Collagen/proteoglycan degradation and pro-inflammatory mediators were monitored in the harvested culture medium of nasal cartilage by estimating the levels of matrix metalloproteinases (MMPs), hydroxy proline, glycosaminoglycans and inflammatory mediators. Further, anti-arthritic ability of GL was evaluated in vivo by measuring enzymatic and non-enzymatic mediators of cartilage degradation, inflammation and oxidative stress markers. Results GL significantly inhibited the IL-1β stimulated cartilage degradation in vitro by mitigating the MMPs activity, collagen degradation and secretion of pro-inflammatory mediators. Further, GL significantly reduced the adjuvant-induced paw swelling and body weight loss in vivo. GL remarkably reduced the MMPs and hyaluronidases activities in serum and bone homogenate along with altered hematological parameters. GL also mitigated the elevated bone resorbing enzymes cathepsins, exoglycosidases and phosphatases. Additionally, GL effectively mitigated ROS and oxidative stress-mediators recuperating the altered serum/liver oxidative stress and liver damage incurred during arthritic progression. Conclusion In summary, the study clearly demonstrates the protective efficacy of GL against arthritis and its associated oxidative stress, particularly, liver oxidative damage. Hence, GL could be a potential alternative and complementary medicine to treat inflammatory joint diseases.

Chikungunya virus, a re-emerging mosquito-borne alphavirus, causes fever, rash and persistent arthralgia/arthritis in humans. Severe outbreaks have occurred resulting in infections of millions of people in Southeast Asia and Africa. Currently there are no antiviral drugs or vaccines for prevention and treatment of chikungunya infections. Herein we report the current status of research on antiviral drugs and vaccines for chikungunya virus infections.