In-vitro antioxidant and anti-inflammatory potential along with p.o. pharmacokinetic profile of key bioactive phytocompounds of Snow Mountain Garlic: a comparative analysis vis-à-vis normal garlic.

Snow mountain garlic (SMG) is a trans-Himalayan medicinal plant used in the traditional medicine system for several ailments, including inflammatory arthritis. Research studies are insufficient to validate its folk medicinal applications. In the present study, the comparative abundance of its key bioactive phytocompounds, viz., S-allyl-L-cysteine (SAC), alliin, and S-methyl-L-cysteine (SMC) against normal garlic were assessed using the LC-MS/MS-MRM method. In addition, the study also explored the antioxidant and anti-inflammatory potency of crude extract of SMG and purified signature phytocompounds (i.e., SMC, SAC, and alliin) in comparison with normal garlic and dexamethasone in LPS-stimulated RAW264.7 macrophage cells. The LC-MS/MS-MRM study revealed significant differences among SMG and normal garlic, viz., alliin 22.8-fold higher in SMG, and SMC could be detected only in SMG. In the bioassays, SMG extract and purified signature phytocompounds significantly downregulated oxidative damage in activated macrophages, boosting endogenous antioxidants' activity. SMG extract-treated macrophages significantly suppressed NF-κB expression and related inflammatory indicators such as cytokines, COX-2, iNOS, and NO. Notably, the observed anti-inflammatory and antioxidant bioactivities of SMG extract were comparable to signature phytocompounds and dexamethasone. In addition, SAC being uniformly found in SMG and normal garlic, its comparative pharmacokinetics was studied to validate the pharmacodynamic superiority of SMG over normal garlic. Significantly higher plasma concentrations (Cmax), half-life (t1/2), and area under curve (AUC) of SAC following SMG extract administration than normal garlic validated the proposed hypothesis. Thus, the abundance of bioactive phytocompounds and their better pharmacokinetics in SMG extract might be underlying its medicinal merits over normal garlic.

Validation of traditional claims of anti-arthritic efficacy of trans-Himalayan snow mountain garlic (Allium ampeloprasum L.) extract using adjuvant-induced arthritis rat model: A comparative evaluation with normal garlic (Allium sativum L.) and dexamethasone.

ETHNOPHARMACOLOGICAL RELEVANCE: Snow Mountain Garlic (SMG) (Allium ampeloprasum L.) is a wild trans-Himalayan member of the genus Allium, valued for its anti-inflammatory and anti-arthritic properties in the mountain folk medicinal system (Sowa-Rigpa). Despite its age-old medicinal usage by traditional therapists and the native population for various ailments including rheumatism, there is no scientific validation of its phyto-pharmaceutical merits. AIM OF THE STUDY: The present pre-clinical study compared the in-vivo anti-arthritic effects of SMG with reported efficacy doses of normal garlic (Allium sativum L.) extract and dexamethasone in a complete Freund's adjuvant (CFA)-induced arthritis rat model. MATERIALS AND METHODS: The female Wistar rats were immunized by the subplannter injection of CFA into the right hind footpad. Aqueous extracts of SMG and normal garlic were administered orally at a dose of 250 mg/kg and 500 mg/kg for 28 days. Dexamethasone was used as positive control drug. Behavioral parameters including paw markers, arthritis index, joint stiffness, body weight change, etc. were measured. Also, the changes in histopathological indices, hematological profile, inflammatory mediators, and serum cytokines level was determined. RESULTS: Treatment of rats with SMG extracts significantly (p < 0.001) prevented the reduction in body weight and hematological changes as well as ameliorated clinical symptoms such as arthritic index, joint stiffness, arthritis score, edema, hyperalgesia, and histopathological indices. This was associated with a significant reduction in the serum levels of RF, CRP, anti-CCP, and proinflammatory cytokines exhibiting strong anti-arthritic potential. SMG extracts could also significantly down regulate the NF-κB, COX-2, and iNOS expression in the ankle joint tissues. CONCLUSIONS: The present study is the first attempt to validate the phyto-pharmaceutical efficacy of this folk garlic variety from the trans-Himalayan region. Overall, SMG extract showed remarkable preventive anti-inflammatory and anti-arthritic activities which were closely comparable to therapeutic effects of dexamethasone and at par or even better than normal garlic w.r.t. several study parameters.

A comparative study of in-vitro and in-silico anti-candidal activity and GC-MS profiles of snow mountain garlic vs. normal garlic.

AIM: The study aimed to profile the volatile phytocomposition of snow mountain garlic (SMG) compared to normal garlic and investigate the anti-Candida efficacy against clinically relevant multi-drug resistant isolates of Candida species. METHODS AND RESULTS: Herein, SMG has shown significantly superior fungicidal power at 2x-MIC dose against C. albicans and C. glabrata in killing kinetic evaluation unlike the fungistatic effect of normal garlic. GC-MS headspace-based profiling of SMG showed 5 unique volatile compounds and a 5-fold higher content of saponins than normal garlic. In an in-silico analysis, cholesta-4,6-dien-3-ol,(3-beta) was uniquely identified in SMG as a potential inhibitor with high binding affinity to the active site of exo-1,3-betaglucan synthase, an established anti-candida drug target crucial for the biofilm matrix formation, thus suggesting a plausible anti-Candida mechanism. CONCLUSION: The in-vitro and in-silico studies have demonstrated the Candida-cidal and anti-biofilm activities of SMG, distinguishing it from the Candida-static efficacy of normal garlic. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report that identifies several phytochemical signatures of SMG along with a potential anti-Candida compound, that is cholesta-4,6-dien-3-ol,(3-beta)-, which appears worthy of detailed studies in the future to explore the utility of SMG as a fungal phytotherapy agent, especially against drug-resistant Candida sp.

Green synthesis of silver nanoparticles using Rhodiola imbricata and Withania somnifera root extract and their potential catalytic, antioxidant, cytotoxic and growth-promoting activities.

This study presents the development of a sustainable production process of environmentally benign silver nanoparticles (AgNPs) from aqueous root extract of Rhodiola imbricata (RI) and Withania somnifera (WS) for mitigating environmental pollution and investigating their potential applications in agriculture and biomedical industry. RIWS-AgNPs were characterized using several analytical techniques (UV-Vis, DLS, HR-TEM, SAED, EDX and FTIR). The antioxidant and anticancer activity of RIWS-AgNPs were estimated by DPPH and MTT assay, respectively. UV-Vis and DLS analysis indicated that equal ratio of RIWS-extract and silver nitrate (1:1) is optimum for green synthesis of well-dispersed AgNPs (λmax: 430 nm, polydispersity index: 0.179, zeta potential: - 17.9 ± 4.14). HR-TEM and SAED analysis confirmed the formation of spherical and crystalline RIWS-AgNPs (37-42 nm). FTIR analysis demonstrated that the phenolic compounds are probably involved in stabilization of RIWS-AgNPs. RIWS-AgNPs showed effective catalytic degradation of hazardous environmental pollutant (4-nitrophenol). RIWS-AgNPs treatment significantly increased the growth and photosynthetic pigments of Hordeum vulgare in a size- and dose-dependent manner (germination (77%), chlorophyll a (12.62 ± 0.07 µg/ml) and total carotenoids (7.05 ± 0.04 µg/ml)). The DPPH assay demonstrated that RIWS-AgNPs exert concentration-dependent potent antioxidant activity (IC50: 12.30 µg/ml, EC50: 0.104 mg/ml, ARP: 959.45). Moreover, RIWS-AgNPs also confer strong cytotoxic activity against HepG2 cancer cell line in dose-dependent manner (cell viability: 9.51 ± 1.55%). Overall, the present study for the first time demonstrated a green technology for the synthesis of stable RIWS-AgNPs and their potential applications in biomedical and agriculture industry as phytostimulatory, antioxidant and anticancer agent. Moreover, RIWS-AgNPs could potentially be used as a green alternative for environmental remediation.

ELONGATED HYPOCOTYL5 Negatively Regulates DECREASE WAX BIOSYNTHESIS to Increase Survival during UV-B Stress.

Understanding how the distinct cell types of the shoot apical meristem (SAM) withstand ultraviolet radiation (UVR) stress can improve cultivation of plants in high-UVR environments. Here, we show that UV-B irradiation selectively kills epidermal and niche cells in the shoot apex. Plants harboring a mutation in DECREASE WAX BIOSYNTHESIS (DEWAX) are tolerant to UV-B. Our data show that DEWAX negatively regulates genes involved in anthocyanin biosynthesis. ELONGATED HYPOCOTYL5 (HY5) binds to the DEWAX promoter elements and represses its expression to promote the anthocyanin biosynthesis. The HY5-DEWAX regulatory network regulates anthocyanin content in Arabidopsis (Arabidopsis thaliana) and influences the survivability of plants under UV-B irradiation stress. Our cell sorting-based study of the epidermal cell layer transcriptome confirms that core UV-B stress signaling pathway genes are conserved and upregulated in response to UV-B irradiation of the SAM. Furthermore, we show that UV-B induces genes involved in shoot development and organ patterning. We propose that the HY5-DEWAX regulatory relationship is conserved; however, changes in the expression levels of these genes can determine anthocyanin content in planta and, hence, fitness under UV-B irradiation stress.

Machine Learning Methods for Computer-Aided Breast Cancer Diagnosis Using Histopathology: A Narrative Review.

Histopathology is a method used for breast cancer diagnosis. Machine learning (ML) methods have achieved success for supervised learning tasks in the medical domain. In this article, we investigate the impact of ML for the diagnosis of breast cancer using histopathology images of conventional photomicroscopy. Cancer diagnosis is the identification of images as cancer or noncancer, and this involves image preprocessing, feature extraction, classification, and performance analysis. In this article, different approaches to perform these necessary steps are reviewed. We find that most ML research for breast cancer diagnosis has been focused on deep learning. Based on inferences from the recent research activities, we discuss how ML methods can benefit conventional microscopy-based breast cancer diagnosis. Finally, we discuss the research gaps of ML approaches for the implementation in a real pathology environment and propose future research guidelines.

Preventive preclinical efficacy of intravenously administered sphingosine-1-phosphate (S1P) in strengthening hypoxia adaptive responses to acute and sub-chronic hypobaric hypoxia.

Sphingosine-1-phosphate (S1P) is emerging as a hypoxia responsive bio-lipid; systemically raised levels of S1P are proposed to have potential hypoxia pre-conditioning effects. The study aims to evaluate the hypoxia pre-conditioning efficacy of exogenously administered S1P in rats exposed to acute (24-48 hs (h)) and sub-chronic (7 days) hypobaric hypoxia. Sprague-Dawley rats (200 ± 20 g) were preconditioned with 1 µg/kg body weight S1P intravenously for three consecutive days. On the third day, control and S1P preconditioned animals were exposed to hypobaric hypoxia equivalent to 7620 m for 24 h, 48 h and 7 days. Post exposure analysis included body weight quantitation, blood gas/chemistry analysis, vascular permeability assays, evaluation of oxidative stress/inflammation parameters, and estimation of hypoxia responsive molecules. S1P preconditioned rats exposed to acute HH display a significant reduction in body weight loss, as a culmination of improved oxygen carrying capacity, increased 2,3- diphosphoglycerate levels and recuperation from energy deficit. Pathological disturbances such as vascular leakage in the lungs and brain, oxidative stress, pro-inflammatory milieu and raised level of endothelin-1 were also reined. The adaptive and protective advantage conferred by S1P in the acute phase of hypobaric hypoxia exposure, is observed to precipitate into an improved sustenance even after sub-chronic (7d) hypobaric hypoxia exposure as indicated by decreased body weight loss, lower edema index and improvement in general pathology biomarkers. Conclusively, administration of 1 µg/kg body weight S1P, in the aforementioned schedule, confer hypoxia pre-conditioning benefits, sustained up to 7 days of hypobaric hypoxia exposure.

Acute Hypobaric Hypoxia-Mediated Biochemical/Metabolic Shuffling and Differential Modulation of S1PR-SphK in Cardiac and Skeletal Muscles.

AIM: High altitude exposure alters biochemical, metabolic, and physiological features of heart and skeletal muscles, and hence has pathological consequences in these tissues. Central to these hypoxia-associated biochemical/metabolic shuffling are energy deficit accumulation of free radicals and ensuing oxidative damage in the tissue. Recent preclinical/clinical studies indicate sphingosine-1-phosphate (S1P) axis, comprising S1P G protein coupled receptors (S1PR1-5) and its synthesizing enzyme-sphingosine kinase (SphK) to have key regulatory roles in homeostatic cardiac and skeletal muscle biology. In view of this, the aim of the present study was to chart the initiation and progression of biochemical/metabolic shuffling and assess the coincident differential modulation of S1PR(1-5) expression and total SphK activity in cardiac and skeletal muscles from rats exposed to progressive hypobaric hypoxia (HH; 21,000 feet for 12, 24, and 48 hours). RESULTS: HH-associated responses were evident as raised damage markers in plasma, oxidative stress, decreased total tissue protein, imbalance of intermediate metabolites, and aerobic/anaerobic enzyme activities in cardiac and skeletal muscles (gastrocnemius and soleus) culminating as energy deficit. CONCLUSION: Cardiac and gastrocnemius muscles were more susceptible to hypoxic environment than soleus muscle. These differential responses were directly and indirectly coincident with temporal expression of S1PR(1-5) and SphK activity.

Enhanced Production of Phenolic Compounds in Compact Callus Aggregate Suspension Cultures of Rhodiola imbricata Edgew.

Rhodiola imbricata is a rare medicinal plant of the trans-Himalayan region of Ladakh. It is used for the treatment of numerous health ailments. Compact callus aggregate (CCA) suspension cultures of Rhodiola imbricata were established to counter extinction threats and for production of therapeutically valuable phenolic compounds to meet their increasing industrial demands. The present study also investigated the effect of jasmonic acid (JA) on production of phenolic compounds and bioactivities in CCA suspension cultures. CCA suspension cultures established in an optimized Murashige and Skoog medium supplemented with 30 g/l sucrose, 3 mg/l NAA, and 3 mg/l BAP showed maximum biomass accumulation (8.43 g/l DW) and highest salidroside production (3.37 mg/g DW). Upon 100 µM JA treatment, salidroside production (5.25 mg/g DW), total phenolic content (14.69 mg CHA/g DW), total flavonoid content (4.95 mg RE/g DW), and ascorbic acid content (17.93 mg/g DW) were significantly increased in cultures. In addition, DPPH-scavenging activity (56.32%) and total antioxidant capacity (60.45 mg QE/g DW) were significantly enhanced upon JA treatment, and this was positively correlated with increased accumulation of phenolic compounds. JA-elicited cultures exhibited highest antimicrobial activity against Escherichia coli. This is the first report describing the enhanced production of phenolic compounds and bioactivities from JA-elicited CCA suspension cultures of Rhodiola imbricata.

Influence of light quality on growth, secondary metabolites production and antioxidant activity in callus culture of Rhodiola imbricata Edgew.

Rhodiola imbricata is a rare medicinal herb well-known for its adaptogenic and antioxidant properties due to the presence of a diverse array of secondary metabolites, including phenylethanoids and phenylpropanoids. These secondary metabolites are generating considerable interest due to their potential applications in pharmaceutical and nutraceutical industries. The present study investigated the influence of light quality on growth, production of industrially important secondary metabolites and antioxidant activity in callus cultures of Rhodiola imbricata. Callus cultures of Rhodiola imbricata were established under different light conditions: 100% red, 100% blue, 100% green, RGB (40% red: 40% green: 20% blue) and 100% white (control). The results showed that the callus cultures grown under red light accumulated maximum amount of biomass (7.43 g/l) on day 21 of culture, as compared to other light conditions. Maximum specific growth rate (0.126 days-1) and doubling time (132.66 h) was observed in callus cultures grown under red light. Reverse phase-high performance liquid chromatographic (RP-HPLC) analysis revealed that the callus cultures exposed to blue light accumulated maximum amount of Salidroside (3.12 mg/g DW) on day 21 of culture, as compared to other light conditions. UV-Vis spectrophotometric analysis showed that the callus cultures exposed to blue light accumulated maximum amount of total phenolics (11.84 mg CHA/g DW) and total flavonoids (5.53 mg RE/g DW), as compared to other light conditions. Additionally, callus cultures grown under blue light displayed enhanced DPPH free radical scavenging activity (53.50%). Callus cultures grown under different light conditions showed no significant difference in ascorbic acid content (11.05-13.90 mg/g DW) and total antioxidant capacity (27.37-30.17 mg QE/g DW). The correlation analysis showed a positive correlation between total phenolic content and DPPH free radical scavenging activity in callus cultures (r = 0.85). Taken together, these results demonstrate the remarkable potential of light quality on biomass accumulation and production of industrially important secondary metabolites in callus cultures of Rhodiola imbricata. This study will open new avenues and perspectives towards abiotic elicitation strategies for sustainable growth and enhanced production of bioactive compounds in in-vitro cultures of Rhodiola imbricata.

The MAPK-activator protein-1 signaling regulates changes in lung tissue of rat exposed to hypobaric hypoxia.

This study reports the role of MAPKs (JNK, ERK, and p38), and activator protein-1 (AP-1) transcription factor in the hypobaric hypoxia induced change in lung tissue. Healthy male Sprague-Dawley rats were exposed to hypobaric hypoxia for 6, 12, 24, 48, 72, and 120 hr. Hypoxia resulted in significant increase in reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and decreased nitric oxide (NO), these act as signaling molecules for activation of MAPK and also contribute in development of vascular leakage (an indicator of pulmonary edema) as confirmed by histological studies. Our results confirmed JNK activation as an immediate early response (peaked at 6-48 hr), activation of ERKs (peaked at 24-72 hr) and p38 (peaked at 72-120 hr) as a secondary response to hypoxia. The MAPK pathway up regulated its downstream targets phospho c-Jun (peaked at 6-120 hr), JunB (peaked at 24-120 hr) however, decreased c-Fos, and JunD levels. DNA binding activity also confirmed activation of AP-1 transcription factor in lung tissue under hypobaric hypoxia. Further, we analyzed the proliferative and inflammatory genes regulated by different subunits of AP-1 to explore its role in vascular leakage. Increased expression of cyclin D1 (peaked at 12-72 hr) and p16 level (peaked at 48-120 hr) were correlated to the activation of c-jun, c-Fos and JunB. Administration of NFκB inhibitor caffeic acid phenethyl ester (CAPE) and SP600125 (JNK inhibitor) had no effect on increased levels of Interferon-γ (IFN-γ), Interleukin-1 (IL-1), and Tumor Necrosis Factor-α (TNF-α) thereby confirming the involvement of AP-1 as well as NFκB in inflammation. Expression of c-jun, c-Fos were correlated with activation of proliferative genes and JunB, Fra-1 with pro-inflammatory cytokines. In conclusion immediate response to hypobaric hypoxia induced c-Jun:c-Fos subunits of AP-1; responsible for proliferation that might cause inhomogeneous vasoconstriction leading to vascular leakage and inflammation at increased duration of hypobaric hypoxia exposure.

Sphingosine-1-phosphate pretreatment amends hypoxia-induced metabolic dysfunction and impairment of myogenic potential in differentiating C2C12 myoblasts by stimulating viability, calcium homeostasis and energy generation.

Sphingosine-1-phosphate (S1P) has a role in transpiration in patho-physiological signaling in skeletal muscles. The present study evaluated the pre-conditioning efficacy of S1P in facilitating differentiation of C2C12 myoblasts under a normoxic/hypoxic cell culture environment. Under normoxia, exogenous S1P significantly promoted C2C12 differentiation as evident from morphometric descriptors and differentiation markers of the mature myotubes, but it could facilitate only partial recovery from hypoxia-induced compromised differentiation. Pretreatment of S1P optimized the myokine secretion, intracellular calcium release and energy generation by boosting the aerobic/anaerobic metabolism and mitochondrial mass. In the hypoxia-exposed cells, there was derangement of the S1PR1-3 expression patterns, while the same could be largely restored with S1P pretreatment. This is being proposed as a plausible underlying mechanism for the observed pro-myogenic efficacy of exogenous S1P preconditioning. The present findings are an invaluable addition to the existing knowledge on the pro-myogenic potential of S1P and may prove beneficial in the field of hypoxia-related myo-pathologies.

S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.

Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 µg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 µg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016.

Comparative Analysis of the Molecular Adjuvants and Their Binding Efficiency with CR1.

There are so many obstacles in developing a vaccine or vaccine technology for diseases like cancer and human immunodeficiency virus infection. While developing vaccines that target specific infection, molecular adjuvants are indispensable. These molecular adjuvants act as a vaccine delivery vehicle to the immune system to increase the effectiveness of the specific antigens. In the present work, a computational study has been done on molecular adjuvants like IgGFc, GMCSF and C3d to find out how efficiently they are binding to CR1. Sequence, structure and mutational analysis are performed on the molecular adjuvants to understand the features important for their binding with the receptor. Results obtained from our study indicate that the adjuvant IgGFc complexed with the receptor CR1 has the best binding efficiency, which can be used further to develop better vaccine technologies.

Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and apoptosis by improving oxidative balance

Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct molecular mechanism underlying the oxidative stress-mediated damages to cardiomyocytes remains unknown. Curcumin(diferuloylmethane) is known for anti-hypertrophic effects, but low bioavailability makes it unsuitable to exploit its pharmacological properties. We assessed the efficacy of nanotized curcumin, i.e. nanocurcumin, in ameliorating hypoxia-induced hypertrophy and apoptosis in H9c2 cardiomyoblasts and compared it to curcumin. H9c2 cardiomyoblasts were challenged with 0.5 % oxygen, for 24 h to assess hypoxia-induced oxidative damage, hypertrophy and consequent apoptosis. The molecular mechanism underlying the protective efficacy of nanocurcumin was evaluated in regulating Raf-1/Erk-1/2 apoptosis by caspase-3/-7 pathway and oxidative stress. Nanocurcumin ameliorated hypoxia-induced hypertrophy and apoptosis in H9c2 cells significantly (p ≤ 0.01), by downregulating atrial natriuretic factor expression, caspase-3/-7 activation, oxidative stress and stabilizing hypoxia-inducible factor-1alfa (HIF-1alfa) better than curcumin. Nanocurcumin provides insight into its use as a potential candidate in curing hypoxia-induced cardiac pathologies by restoring oxidative balance

Nanocurcumin protects cardiomyoblasts H9c2 from hypoxia-induced hypertrophy and apoptosis by improving oxidative balance.

Hypoxia-induced cardiomyocyte hypertrophy is evident; however, the distinct molecular mechanism underlying the oxidative stress-mediated damages to cardiomyocytes remains unknown. Curcumin (diferuloylmethane) is known for anti-hypertrophic effects, but low bioavailability makes it unsuitable to exploit its pharmacological properties. We assessed the efficacy of nanotized curcumin, i.e. nanocurcumin, in ameliorating hypoxia-induced hypertrophy and apoptosis in H9c2 cardiomyoblasts and compared it to curcumin. H9c2 cardiomyoblasts were challenged with 0.5 % oxygen, for 24 h to assess hypoxia-induced oxidative damage, hypertrophy and consequent apoptosis. The molecular mechanism underlying the protective efficacy of nanocurcumin was evaluated in regulating Raf-1/Erk-1/2 apoptosis by caspase-3/-7 pathway and oxidative stress. Nanocurcumin ameliorated hypoxia-induced hypertrophy and apoptosis in H9c2 cells significantly (p ≤ 0.01), by downregulating atrial natriuretic factor expression, caspase-3/-7 activation, oxidative stress and stabilizing hypoxia-inducible factor-1α (HIF-1α) better than curcumin. Nanocurcumin provides insight into its use as a potential candidate in curing hypoxia-induced cardiac pathologies by restoring oxidative balance.

Comparative analysis of the molecular adjuvants and their binding efficiency with CR1.

There are so many obstacles in developing a vaccine or vaccine technology for diseases like Cancer and Human Immunodeficiency Virus (HIV) infection. While developing vaccines that targets specific infection, molecular adjuvants are indispensable. These molecular adjuvants act as a vaccine delivery vehicle to the immune system to increase the effectiveness of the specific antigens. In the present work, a computational study has been done on molecular adjuvants like IgGFc, GMCSF and C3d to find out how efficiently they are binding to CR1. Sequence, structure and mutational analysis are performed on the molecular adjuvants to understand the features important for their binding with the receptor. Results obtained from our study indicate that the adjuvant IgGFc complexed with the receptor CR1 has the best binding efficiency, which can be used further to develop better vaccine technologies.