Alveolar bone atrophy after tooth extraction presents significant difficulties when planning delayed-immediate implant treatment to replace a lost tooth. Socket augmentation is an effective therapy that limits the post extraction volumetric changes and facilitates implant placement whilst reducing the need for staged grafting. However, socket augmentation and osteoconductive graft conversion is a slow process that could take 4-6 months. PRF and its variants have significant bio-enhancement effect on wound healing and regeneration through release of platelet drived growth factors, bioactive substances, cytokines. Leukocytes in PRF also play a significant role in enhancing tissue regeneration as part of osteo-immune response. Use of PRF during socket augmentation is highly effective in enhancing extraction site healing and graft integration by angiogenesis, cell proliferation, recruitment, and differentiation through release of growth factors and bioactive substances mediated by platelets and leukocytes. PRF with SA is recommended as an adjunct to SA as a sole biomaterial or in combination with xenograft or allograft bone substitutes to enhance tissue regeneration and to reduce risk of infection, osteitis and postoperative pain in extraction sockets

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disorder which is characterized by fibrofatty degeneration of cardiac muscles mainly in the right ventricular myocardium. It may cause tachyarrhythmias or right-heart failure or may cause sudden death, especially in young athletes. In our case report, we present a case of young age male patient who presented at a local community hospital with the complaint of atypical chest pain, palpitations, and vomiting and sustained ventricular tachycardia (VT) on electrocardiograph (ECG) showing sustained ventricular tachycardia, left bundle branch morphology with the superior axis. The normal sinus rhythm was achieved after multiple DC cardioversion attempts and he was referred to our tertiary care hospital. Later ECG demonstrated epsilon waves and T wave inversion in v1 to v4 and RBBB morphology. The echocardiography showed a severely dilated right ventricle with dysfunction and right ventricle ventricular apical aneurysm. The definitive diagnosis of ARVC was made as per Revised Task Force Criteria 2010 and the electrophysiology review suggested implantable cardiac defibrillator (ICD) device placement. The patient successfully received a dual-chamber ICD device and he remained asymptomatic.

The purpose of this study is to determine the relationship between grit and parenting style of mother among Indian rural adolescents. Parental Authority Questionnaire [1] and Short Grit Scale [2] was used to meet objectives of the paper. A sample of 60 adolescents was chosen from private institution located at Bathinda (Punjab) by using convenience sampling technique. Results of correlation analysis revealed that significant (negative) relationship exists between mother’s authoritarian parenting style (only) and grit. This is true for both genders and for adolescents who comes from joint families. Educational implication of the study signifies that the suitable informative and counseling sessions should be organised for the parents to make them conscious of the appropriate parenting style for the development of gritty adolescents.

Hypertrophic obstructive cardiomyopathy (HOCM) is an autosomal dominant disorder leading to left ventricular outflow tract obstruction (LVOTO). It can present with chest pain, syncope, breathlessness, or in some cases sudden cardiac death. Primarily, it is diagnosed based on echocardiographic findings but cardiac computed tomography (CT) or cardiac magnetic resonance imaging (MRI) can be helpful in selected cases. In this case report, we discuss a case of a young-aged female patient previously diagnosed as HOCM and presented with chest pain, shortness of breath, and palpitations. Her echocardiography revealed severe asymmetrically hypertrophied left ventricle (LV) with normal function and systolic anterior motion of the mitral valve was present and a subvalvular aortic membrane was also seen. The computed tomography (CT) was also performed showing severe asymmetrical hypertrophied and thickened trileaflet tricommissural aortic valve with no calcification or significant valvular aortic stenosis but there was a subaortic membrane (concentric only sparing anteriorly). The presence of subaortic membrane with HOCM is a rare finding and it can be a diagnostic challenge and untreated cases are susceptible to progressive heart failure and worsening of the symptoms by further increasing left ventricular outflow tract obstruction (LVOTO). A thorough investigation and planning before surgical intervention is required to achieve optimal results.

Micro-expression (ME) is one of the key psychological stress reactions. It is a modest, spontaneous facial mechanism. ME has significant applicability in a variety of psychologically-related sectors because to its precision and unpredictability with regard to psychological manifestations. Nevertheless, the current Micro-expression recognition (MER) algorithms have poor accuracy and a limited quantity of ME data, and this study issue has not been thoroughly investigated. Therefore, we present an approach for deep learning based on a Spatio-temporal capsule network (STCP-Net). STCP-Net has four components: a jitter reduction module, a differential feature extraction module, an STCP module, and a fully linked layer. The first two modules are aimed to extract diversifying differential features more precisely and to limit the influence of head jitter. The STCP module is used to extract Spatio-temporal features layer by layer, taking the temporal and geographical connection between features into account. This research runs sufficient trials using the Leave One Subject Out (LOSO) methodology for cross-validation using the CASMEII dataset. The conclusion and analysis demonstrate that the algorithm is innovative and efficient.

A huge number of applications available for Android-based smartphone devices have emerged over the past years. Due to which a huge number of malicious applications has been growing explosively. Many approaches have been proposed to ensure the security and quality of application in the markets. Usually, Machine Learning approaches are utilized in the classification process of malicious application detection. Calculating accurate results of characterizing applications behaviors, or other features, has a direct effect on the results with Machine Learning calculations. Android applications emerge so quickly. The behavior of current applications has gotten progressively malicious. The extraction of malware-infected features from applications is thus become a difficult task. According to our knowledge, a ton of features have been extricated in existing work however no survey has overviewed the features built for identifying malicious applications efficiently. In this paper, we will in general give an extensive review of such sort of work that identifies feature applications by describing various practices of uses with various kinds of features. In this survey we have discussed the following dimensions: extraction and selection of feature methods if any, methods of detection and evaluation performed. In light of our review, we notice the issues of investigating malware-affected features from applications, give the scientific categorization and demonstrate the future headings.

Among the leading causes of cancer mortality, prostatic adenocarcinoma (PaC) is at second to lung carcinoma, but it is the most commonly happening non-cutaneous malignancy in elderly men in the world. Therapeutic options for PaC depend on age, growth & stage of malignancy, the desired outcomes and shortcomings of available treatment, estimated cost and patient compliance. Patients older than 60 years with a sluggish localized tumor may be placed on active surveillance, otherwise go with transurethral resection of the prostate (TURP), prostate artery embolization (PAE) and pelvic lymphadenectomy with/without radiation therapy. For metastatic PC androgen-deprivation therapy is an option with or without surgery. These agents decline the body’s testosterone production or block its activity by gonadotropin- releasing hormone (GnRH) analogues including leuprolide acetate and goserelin acetate implant. The hormone’s activity can be stopped by androgens antagonist such as flutamide, bicalutamide and nilutamide along with chemotherapeutic agents, such as taxanes (e.g., docetaxel, paclitaxel) but after all the disease relapses in 20-30% of patients. So, new immunological or vaccine-based therapeutic moieties have been investigated to meet the objective of providing selectivity to cancerous cells and desired therapeutic outcomes with less/no harmful effects to normal cells. The chimeric version, oncolytic poliovirus and human rhinovirus i.e. PVSRIPO is most promising feature in cancer therapeutics and activate innate immunity by neutrophils infiltration via PAMP & DAMP pathways while Sipuleucel-T expresses major histocompatibility complex (MHC) which can stimulate CD4+ helper T-cells and CD8+ cytotoxic T-cells and ultimately activate the acquired immunity against cancer cells. In this article, we have discussed the role of genetic predisposition and chemotherapeutic approaches including oncolytic poliovirus for the treatment of PaC in order to better understanding of tumor biology and mechanisms involved in chemotherapeutic drugs based resistance.

Windup, a progressive increase in spinal response to repetitive stimulations of nociceptive peripheral fibres, is a useful model to study central sensitization to pain. Windup is expressed by neurons in of both dorsal and ventral horn of the spinal cord. In juvenile rats, it has been demonstrated both in vivo and in vitro that windup depends on calcium-dependent intrinsic properties and their modulation by synaptic components. However, the involvement of these two components in the adult remain controversial. In the present study, by means of electromyographic and extracellular recordings, we show that windup in adult, in vivo, depends on a synaptic balance between excitatory NMDA receptors and inhibitory glycinergic receptors. We also demonstrate the involvement of L-type calcium channels in both the dorsal and ventral horn of the spinal cord. These results indicate that windup in adults is similar to juveniles rats and that windup properties are the same regardless spinal network, i.e. sensory or motor.

A newly identified novel coronavirus named as severe acute respiratory syndrome-related coronavirus2 (SARS‐CoV 2) has given rise to the global pandemic. SARS-CoV2 which causes coronavirus disease 2019 (COVID-19), is a positive-stranded RNA virus with nucleocapsid. It binds to host angiotensin-converting enzyme2 (ACE2) receptor through surface glycoprotein (S protein). These ACE 2 receptors are attached to the cell membranes of many organs. Thus, COVID-19 does not only result in acute respiratory distress syndrome but also affects multiple organ systems, requiring a multidisciplinary approach to manage this disease. COVID-19 can damage the myocardial cells and result in fulminant myocarditis, acute cardiac injury, cardiomyopathy, heart failure, cardiogenic shock, or arrhythmia. COVID-19 seeds harmful immune response through cytokine storm leading to indirect organ damage. In this literature review, the available data is comprehended regarding cardiovascular complications in COVID-19, and the correlation of biomarkers with the disease activity is discussed. This literature review also highlights the important treatment options and outcomes of the individual study.

In the study of QSAR/QSPR, due to high degree of predictability of pharmaceutical properties, the eccentric-connectivity index has very important place among the other topological descriptors, In this paper, we compute the exact formulas of eccentric-connectivity index and its corresponding polynomial, total eccentric-connectivity index and its corresponding polynomial, first Zagreb eccentricity index, augmented eccentric-connectivity index, modified eccentric-connectivity index and its corresponding polynomial for a class of phosphorus containing dendrimers.

Covid-19 is an airborne disease, with the vast majority of infections occurring indoors. By comparison, little transmission occurs outdoors. Here, we investigate the airborne transmission pathways that differentiate the indoors from outdoors, and conclude that profound differences exist, which help to explain why SARS-CoV-2 transmission is much more prevalent indoors. Near and far-field transmission pathways are discussed along with factors that affect infection risk, with aerosol concentration, air entrainment, thermal plumes, and occupancy duration all identified as being influential. In particular, we present the fundamental equations that underpin the Wells-Riley model, and show the mathematical relationship between inhaled virus particles and quanta of infection. A simple model is also presented for assessing infection risk in spaces with incomplete air mixing. Transmission risk is assessed in terms of aerosol concentration using simple 1D equations, followed by a description of thermal plume-ceiling interactions. With respect to this, we present new experimental results using Schlieren-visualisation and Computational Fluid Dynamics (CFD) based on the Eulerian-Lagrangian approach. Pathways of airborne infection are discussed, with the key differences identified between indoors and outdoors. In particular, the contribution of thermal and exhalation plumes is evaluated, and the presence of near-field/far-field feedback loop postulated, which is absent outdoors.

The human respiratory syncytial virus (hRSV) poses a serious risk to global public health and is a significant cause of severe lower respiratory infections. There are currently only a few therapies available to treat RSV infections, as well as no RSV vaccinations. Therefore, there is an urgent demand for clinically feasible, safe, and affordable RSV prevention and treatment alternatives. In this study, an ion-activated in situ gel comprising broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) for antiviral action on RSV was developed. In this content, mechanical properties, sprayability, drug content, pH, ex vivo mucoadhesive strength, in vitro drug release pattern, and stability were all examined. Rheological properties were also tested by utilizing in vitro gelation capacity and rheological synergism tests. Finally, the optimized in situ gel's cytotoxic and antiviral activities on RSV cultured in human laryngeal epidermoid carcinoma (HEP-2) cell line were evaluated. In conclusion, the optimized in situ gel prepared with a combination of 0.5%w/w gellan gum and 0.5%w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between T0 and T14: 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53), mechanical characteristics (adhesiveness: 0.300 mJ ± 0.05), ex vivo bioadhesion force (19.67 g ± 1.90), drug content uniformity (RSD%: 0.494), and sustained drug release over period of 168 h (101.57% ± 0.53). The antiviral activity test results showed that the optimized in situ gel had strong anti-HRSV activity (EC50 simultaneous = 0.05 µg/ml, SI = 306; EC50 preinfection = 0.154 µg/ml, SI= 100) which was significantly higher than that of ribavirin (EC50 =4.189 µg/ml; SI= 28) used as a positive control against hRSV. In conclusion, this research has demonstrated the formulation of an effective antiviral nasal spray that has the ability to possess both prophylactic and virucidal activity.

Mercury (Hg (II)) contamination is indefatigable global hazard which causes severe permanent damages to human health. Extensive research has been carried out to produce mercury adsorbents however they are still facing certain challenges limiting their upscaling. Herein we reported the synthesis of novel amine impregnated inverse vulcanized copolymer for effective mercury removal. Poly(S-MA) was prepared using sulfur and methacrylic acid employing inverse vulcanization method following by functionalization. The polyethylenime (PEI) was impregnated on poly(S-MA) to increase the adsorption active sites. The developed adsorbent was then characterized using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). FTIR confirmed formation of copolymer and successful impregnation of PEI and SEM revealed composite porous morphology of the copolymer. Amine impregnated copolymer (amine@poly(S-MA)) outperformed poly(S-MA) in mercury as it showed 20 % superior performance with 44.7 mg/g maximum adsorption capacity. The adsorption data best fits the pseudo second order which indicates that the chemisorption is most influential mechanism in this case indicating the involvement of NH2 in mercury removal. The adsorption is mainly monolayer on homogenous surface as indicated by 0.76 value of Redlich-Peterson exponent (g) which describes the adsorption nature advent from R2 value of 0.99.

Diabetes mellitus leads to cardiovascular complications including impaired cardiac β-adrenoceptor (β-AR) function. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as empagliflozin (EMPA) improve outcomes in heart failure patients and animal models thereof. Therefore, we have investigated the effects of EMPA on in vivo cardiac function (pressure-volume loop analysis) and β-AR-mediated contractile responses (papillary strips) in streptozotocin (STZ; 40 mg/kg, i.p.)-induced diabes in male Sprague Dawley rats (control, EMPA-treated control, diabetic, EMPA-treated diabetic) in a design reflecting late-onset treatment. 13-16 weeks after STZ injection treatment with a low dose of EMPA (10 mg/kg/day, daily oral gavage) or vehicle was administered for another 8 weeks. EMPA did not change cardiac function in control rats. Diabetic rats had a reduced heart rate, cardiac output, stroke work, rate of contration and rate of relaxation and increased isovolumic relaxation, whereas in vitro responses were not markedly attenuated. Treatment with EMPA showed a trend for improvement of some but not all parameters. Our results indicate that low dose EMPA treatment had limited effects on cardiac impairment despite reducing blood glucose when initiated after diabetes is manifest. Future studies with a higher dose and greater sample sizes could help to clarify the possible benefits of EMPA on the diabetic heart.

The goal of the current study is to analyse several nonlinear two-dimensional time-fractional Rosenau Hymanequations. The two-dimensional fractional Rosenau-Hyman equation has extensive use in engineering and applied sciences. The fractional view analysis of two-dimensional time-fractional Rosenau-Hyman equations is discussed using the homotopy perturbation approach, adomian decomposition method, and Yang transformation. Some examples involving two-dimensional time-fractional Rosenau-Hyman equations are provided in order to better understand the suggested approaches. The solutions appear as infinite series. We offer a comparison between the accurate solutions and those that are generated employing the proposed approaches in order to demonstrate the effectiveness and applicability of the proposed techniques. The results are graphically illustrated using 2D and 3D graphs. It has been noted that the obtained results and the targeted problems real solutions are quite similar. Calculated solutions at various fractional levels describe some of the problems useful dynamics. Other fractional problems that arise in other fields of science and engineering can be solved using a modified version of the current techniques.

It is a challenging problem that air-written Arabic letters has received a lot of attention in the past decades when compared to commonly spoken languages like English languages. To fill this gap, we propose a strong model that brings together machine learning (ML) and optical character recognition (OCR) methods. The model applied several ML methods, (i.e., Neural Networks (NN), Random Forest (RF), K-Nearest Neighbors (KNN), and Support Vector Machine (SVM), with deep convolutional neural networks (CNNs) such as VGG16, VGG19, and SqueezeNet for effective feature extraction. Our study utilizes the AHAWP dataset, which consists of varied writing styles and variations in hand signs, to train and evaluate the model. Preprocessing systems are applied to improve data quality by reduction bias. Besides, OCR methods are combined into our model to sequestrate individual letters from continuous air-written gestures and refine recognition results. Results of this study show that the proposed model has achieved the extreme accuracy of 88.8% using NN with VGG16. This study presents an inclusive approach that combines ML, deep CNNs, and OCR methods to address the issue of Arabic in air writing recognition research.

Monkeypox virus belongs to the Orthopoxvirus genus, which belongs to the Poxviridae family. The Monkeypox virus is responsible to cause monkeypox, a developing zoonotic disease that has been identified as the most common orthopoxvirus infection in humans in the post-eradication era of smallpox. The virus can be transmitted by a variety of animals, including monkeys and rodents as well as person-to-person. Monkeypox has a clinical presentation that is quite similar to smallpox but mortality is low, in that the febrile prodrome is followed by a period of skin eruption. Monkeypox cases have extended outside the forests of central Africa, where they were first discovered, to other regions of the globe, where they have been imported. This pattern of transmission is most likely related to a global reduction in orthopoxvirus immunity following the discontinuation of smallpox vaccination in 1980, when smallpox was proclaimed eliminated. As a result, monkeypox might become the very common orthopoxvirus infection that affect humans. The emergence of epidemics outside of Africa emphasizes the disease's global significance. Increased monitoring and identification of monkeypox cases are critical tools for gaining a better knowledge of the disease's ever-changing epidemiology.

Cobalt (Co) is a transition metal and is classified as a beneficial metal for plants, but its benefits for plants remain obscure. Cobalt has been reported to negatively affect plant physiochemical processes both at higher (toxic) and lower (deficient) applied levels. High concentrations of cobalt in plant organs cause irreversible changes to the plant cells, mainly via enhanced production of reactive radicals. Moreover, Co and its compound play an essential role in humans as they are the central atoms of cobalamin, a co-enzyme precursor whose absence causes anemia. Hence, the optimum Co supply to plants is critical for customary plant metabolic workings. Henceforth, monitoring Co behavior in the soil-plant-human system is highly imperative. This review highlighted the latest literature on (i) Co in soil and plants; (ii) its mobility and phyto-availability in soil; (iii) phytouptake and translocation towards shoot tissues; (iv) toxic and deficient effects of Co on plants; (v) plant detoxification mechanisms under increased Co levels inside plants; and (v) its role in the human body. For this purpose, 1026 plant observations from literature data were analyzed related to Co biogeochemical behavior in the soil-plant system. The data analysis revealed an overall increase in 567 observations and a decrease in 381 observations. However, these general trends in plant responses vary significantly for different types of plant species and physiological attributes. Overall, the current review delineates an updated and critical representation of the biogeochemical behavior of Co in the soil-plant-human system, supported by up-to-date 9 main tables, 14 supporting tables, and 3 figures. The authors believe that the literature presented here can be of great interest to scientists, researchers, policymakers, and graduate-level students.

Seaweeds are considered as one of the largest biomass producers in marine environment that is rich in bioactive metabolites and a source of natural ingredients for functional foods. The potential antioxidant activity and the potential inhibition of Caco2 cell proliferation, of crude extracts of: Chlorophyta (Ulva lactuca, and Codium tomentosum), Phaeophyta (Cystoseira crinita, Cystoseira stricta, and Sargassum vulgare), and Rhodophyta (Gelidium latifolium, Hypnea musciformis, and Jania rubens) collected from western Libyan coast were evaluated in vitro. The antioxidant activity was determined by reducing power and DPPH assays while cell proliferation, morphological changes and the cell cycle arrest were assessed by MTT, inverted light microscope and flow cytometry methods respectively. The polyphenols and flavonoids rich extracts showed remarkable reducing power and antiradical properties. After exposure of Caco2 cells to; various concentrations of extracts (50, 100,150 and 200 µg/mL) especially from brown algae for 72 h, significantly reduced cell proliferation. The antiproliferative effect of algae extracts was correlated with their polyphenol and flavonoid contents. Cell cycle analysis further showed that cells were arrested in G phases along with an increment in sub-diploidal cell population (sub-G) after extract application. These results imply that seaweeds which are rich in bioactive compounds may be in anticancer drug research programs. However, further investigations are essential to reveal the molecular mechanisms of the anticancer activities of these algae.

Pathogenesis of aortic aneurysm and dissection continues to be under discussion. Extracellular matrix (ECM) remodeling processes in the aortic wall are hypothesized to be involved in the development of the disorders. Therefore, in a histological study, we investigated the expression of metalloproteases 1 and 9 (MMP1 and MMP9) and their inhibitors (TIMP 1 and TIMP 2) in cardiac surgery patients. In parallel, we studied the aortic roots by echocardiography. Clinical reports of 111 patients (30 women and 81 men) who suffered from aortic aneurysms and an aortic dissection were evaluated and studied by transesophageal echocardiography. Seven patients, who had coronary heart disease served as „healthy controls“ All patients were surgically operated in the period from 2007 to 2015. A tissue sample of the aortic biopsies was collected from each patient during surgery. Immunohistochemical staining was performed for MMP1, MMP9 and TIMP1, TIMP2 as well. Vascularization was monitored by an CD 31 antibody. In direct comparison, the expressions are not homogeneous. We found smallest changes in the intima area at all. An increase in MMP 1 and MMP 9 expression was detected in both media and adventitia in case of dissections. TIMP 1 and TIMP 2 distribution increases from the lumen of the vessel outward in the wall layers of the aorta. In case of arteriosclerotic changes, intima had a capillarization, but not in the media. Opposite pattern was found in the dissected aortas. Whereas the intima appears empty, vascularization was found in the media and adventitia layers, as well. There are differences in the vascularization between between the aneurysm and dissection and the different layers as well, respectively. A different remodeling process of the ECM in comparison of the vascular layers must be hypothesized. Reading the patterns of staining and with regard to the known inhibitory effect of MMP9 on ECM remodeling, but especially TIMP 2 on neoangiogenesis, a disturbed nutrition and a dysfunctional vasa vasorum remodeling must be assumed as cause of dissection.

Hydrogels can provide instant relief to pain and facilitate the fast recovery of wounds. Currently the incorporation of medicinal herbs/plants in polymer matrix is being investigated due to their anti-bacterial and wound healing properties. Herein, we investigated the novel combination of chitosan (CS), chondroitin sulfate (CHI) and garlic (Gar) to synthesize hydrogels through freeze gelation process for faster wound healing and resistance to microbial growth at the wound surface. The synthesized hydrogels were characterized via Fourier transform infrared spectroscopy (FTIR), which confirmed the presence of relevant functional groups. The scanning electron microscopy (SEM) images exhibited the porous structure of the hydrogels, which is useful for the sustained release of Gar from the hydrogels. The synthesized hydrogels showed significant inhibition zones against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, cell culture studies confirmed the cyto-compatibility of the synthesized hydrogels. Thus, the novel hydrogels presented in this study can offer antibacterial effect during wound healing and promote tissue regeneration.

Three-choice preferences for fermented sorghum teas (FST) were examined among 11 adult Ossabaw pigs. The objectives for experiments 1 and 2 (respectively) were to determine preference for: 1) one of three types of FST (white vs. sumac vs. roasted sumac), and 2) isocaloric control (+control; made isocaloric with sucrose), blended FST (3Tea; equal parts of white, sumac, and roasted-sumac), or a negative control (-control; distilled water; avoidance). Pigs were first conditioned to navigate a three-choice preference maze. For experiment 1, no clear preference behaviors for tea-type were observed. Pigs consumed nearly all the teas, but pigs consumed the least amount of tea in the first session. Pigs spent the most time with their heads in the bowl when 3Tea was offered, followed by +control, and the least time was -control.  Regardless of tea-type, adult pigs show a strong preference for FST, even over +control, which was sweetened water. Adult pigs likely prefer the complexity of flavors, rather than the sweetness alone.  Future projects that explore the health benefits of this sorghum formula will not be impeded by avoidance among adult pigs.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Aspalathin (ASP) can protect H9c2 cardiomyocytes against high glucose (HG)-induced shifts in myocardial substrate preference, oxidative stress and apoptosis. While the protective mechanism of aspalathin remains unknown, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has emerged as a key factor for intracellular responses against oxidative stress. Therefore, we hypothesized that aspalathin protects the myocardium against hyperglycemia-induced oxidative damage by up-regulating Nrf2 expression in H9c2 cardiomyocytes and diabetic (db/db) mice. Using an oxidative stress RT2 Profiler PCR array, ASP at a dose of 1 µM was demonstrated to protect H9c2 cardiomyocytes against HG-induced oxidative stress, but silencing of Nrf2 abolished this protective response of ASP and exacerbated cardiomyocyte apoptosis. Db/db mice and their non-diabetic (db/+) littermate controls were subsequently treated daily for 6 weeks with either a low (13 mg/kg) or high (130 mg/kg) ASP dose. Compared to nondiabetic mice the db/db mice presented increased cardiac remodeling and enlarged left ventricular wall that occurred concomitant to enhanced oxidative stress. Daily treatment of mice with ASP at a dose of 130 mg/kg for 6 weeks was more effective at reversing complications than both a low dose ASP or metformin, eliciting enhanced expression of Nrf2 and its downstream antioxidant genes. These results indicate that ASP maintains cellular homeostasis and protects the myocardium against hyperglycemia-induced stress through activation of Nrf2 and its downstream target genes.