A photothermal driven chemotherapy for the treatment of metastatic melanoma.

Solid tumors are abnormal mass of tissue, which affects the organs based on its malignancy and leads to the dysfunction of the affected organs. The major problem associated with treatment of solid tumors is delivering anticancer therapeutics to the deepest layers/core of the solid tumor. Deposition of excessive extracellular matrix (ECM) hinders the therapeutics to travel towards the core of the tumor. Therefore, conventional anticancer therapeutics can only reduce the tumor size and that also for a limited duration, and tumor recurrence occurs once the therapy is discontinued. Additionally, by the time the cancer is diagnosed, the cancer cells already started affecting the major organs of the body such as lung, liver, spleen, kidney, and brain, due to their ability to metastasize and lung is the primary site for them to be infiltrated. To facilitate the anticancer therapeutics to penetrate the deeper layers of tumor, and to provide concurrent treatment of both the solid tumor and metastasis, we have designed and developed a Bimodal Light Assisted Skin Tumor and Metastasis Treatment (BLAST), which is a combination of photothermal and chemotherapeutic moieties. The BLAST is composed of 2D boron nitride (BN) nanosheet with adsorbed molecules of BCL-2 inhibitor, Navitoclax (NAVI) on its surface, that can breakdown excessive ECM network and thereby facilitate dissociation of the solid tumor. The developed BLAST was evaluated for its ability to penetrate solid tumors using 3D spheroids for the uptake, cytotoxicity, growth inhibition, reactive oxygen species (ROS) detection, penetration, and downregulation of proteins upon laser irradiation. The in vivo therapeutic studies on a skin cancer mice model revealed that the BLAST with and without laser were able to penetrate the solid tumor, reduce tumor volume in mice, dissociate the protein network, and prevent lung metastasis as confirmed by immunohistochemistry and western blot analysis. Post analysis of serum and blood components revealed the safety and efficacy of BLAST in mice. Hence, the developed BLAST holds strong promise in solid tumor treatment and metastasis prevention simultaneously.

Photoperiod-driven concurrent changes in hypothalamic and brainstem transcription of sleep and immune genes in migratory redheaded bunting.

The molecular regulation of sleep in avian migrants is still obscure. We thus investigated this in migratory redheaded buntings, where four life-history states (LHS; i.e. non-migratory, pre-migratory, migratory and refractory states) were induced. There was increased night-time activity (i.e. Zugunruhe) during the migratory state with reduced daytime activity. The recordings of the sleep-wake cycle in buntings showed increased night-time active wakefulness coupled with drastically reduced front and back sleep during migratory phase. Interestingly, we found the buntings to feed and drink even after lights-off during migration. Gene expression studies revealed increased hypothalamic expression of glucocorticoid receptor (nr3c1), and pro-inflammatory cytokines (il1b and il6) in pre-migratory and migratory states, respectively, whereas in brainstem Ca2+/calmodulin-dependent protein kinase 2 (camk2) was upregulated during the migratory state. This suggested a heightened pro-inflammatory state during migration which is a feature of chronic sleep loss, and a possible role of Ca2+ signalling in promoting wakefulness. In both the hypothalamus and brainstem, the expression of melatonin receptors (mel1a and mel1b) was increased in the pre-migratory state, and growth hormone-releasing hormone (ghrh, known to induce sleep) was reduced during the migratory state. The current results demonstrate key molecules involved in the regulation of sleep-wake cycle across LHS in migratory songbirds.

Dynamic change in optical properties of a nanoparticle embedded tumor phantom for plasmonic photothermal cancer therapeutics.

In this study, the temporal dynamic changes in optical properties of gold nanorods (GNR) embedded tumor phantom, during photothermal interaction, are reported for plasmonic photothermal therapeutics. Tumor mimicking bilayer phantoms were prepared by using 1% agarose incorporated with 0.1% coffee powder, 0.3% intralipid solution as epidermis layer; 3% intralipid solution and 0.3% human hemoglobin (Hb) powder as dermis layer. On incorporating GNRs of concentrations 10, 20, and 40 µg/ml within the phantom, the absorption coefficients increases 4-8 times, while there is minimal change in the reduced scattering coefficients. Further the absorption coefficient increased by ~8% with the incorporation of GNRs of concentration 40 µg/ml, while no considerable dynamic change in the optical properties is observed for the phantom embedded with GNRs of concentrations 10, and 20 µg/ml. The discussed results are useful for the selection of GNRs dose for pre-treatment planning of plasmonic photothermal cancer therapeutics.

Agronomic biofortification of food crops: An emerging opportunity for global food and nutritional security.

Fortification of food with mineral micronutrients and micronutrient supplementation occupied the center stage during the two-year-long Corona Pandemic, highlighting the urgent need to focus on micronutrition. Focus has also been intensified on the biofortification (natural assimilation) of mineral micronutrients into food crops using various techniques like agronomic, genetic, or transgenic. Agronomic biofortification is a time-tested method and has been found useful in the fortification of several nutrients in several crops, yet the nutrient use and uptake efficiency of crops has been noted to vary due to different growing conditions like soil type, crop management, fertilizer type, etc. Agronomic biofortification can be an important tool in achieving nutritional security and its importance has recently increased because of climate change related issues, and pandemics such as COVID-19. The introduction of high specialty fertilizers like nano-fertilizers, chelated fertilizers, and water-soluble fertilizers that have high nutrient uptake efficiency and better nutrient translocation to the consumable parts of a crop plant has further improved the effectiveness of agronomic biofortification. Several new agronomic biofortification techniques like nutripriming, foliar application, soilless activation, and mechanized application techniques have further increased the relevance of agronomic biofortification. These new technological advances, along with an increased realization of mineral micronutrient nutrition have reinforced the relevance of agronomic biofortification for global food and nutritional security. The review highlights the advances made in the field of agronomic biofortification via the improved new fertilizer forms, and the emerging techniques that achieve better micronutrient use efficiency of crop plants.

Pulmonary Dysfunction in Transfusion-Dependent Thalassemia and Response to Intensive Chelation Therapy.

OBJECTIVE: To evaluate pulmonary functions in children with transfusion-dependent thalassemia, and its reversal (lung dysfunction) using intensive intravenous chelation with desferrioxamine (DFO) (4 weeks). METHODS: This descriptive study enrolled 77 children with transfusion-dependent thalassemia. Pulmonary function test (PFT) and iron load (serum ferritin (SF) and T2* MRI of heart and liver) were done. PFT included spirometry, total lung capacity (TLC) by helium dilution test and diffusion capacity by carbon monoxide (DLCO). Follow-up PFT was available for 13 children with moderate to severe lung dysfunction given intravenous DFO. RESULTS: 50 (68.8%) patients had lung dysfunction, most commonly diffusional impairment (48; 96%), and reduced TLC (11; 22%); and none had obstructive pattern. 9 (81.8%) patients with restrictive defect had moderate to severely deranged DLCO. PFT and T2* MRI values were inversely correlated with serum ferritin. Among 13 patients receiving intensive chelation for 4 weeks, significant improvement was noticed in forced expiratory volume in one minute/ forced vital capacity ratio (DFEV1/FVC) (P=0.009), DDLCO (P=0.006) and DSF (P=0.01). CONCLUSIONS: Pulmonary dysfunction is common in children with multi-transfused thalassemia, and routine screening by PFT needs to be part of the management guidelines.

Effect of Astaxanthin and Copper Supplementation on Growth, Immunity, Antioxidant, and Blood Biochemical Status of Growing Murrah Buffalo Heifers.

This study was aimed to explore the effect of astaxanthin (ASTX) and copper (Cu) supplementation on the growth, immunity, antioxidant, and blood biochemical status of growing Murrah buffalo heifers. Twenty-eight Murrah buffalo heifers were selected and randomly divided into 4 groups (n = 7) after blocking by body weight (BW) (129.86 ± 5.37 kg) and age (9.05 ± 1.02 months). The heifers were fed basal total mixed ration diet without supplementation (CON) or with ASTX (0.20 mg/kg BW; AX), Cu (10 mg/kg DM; CU), or ASTX + Cu (0.20 mg/kg BW + 10 mg/kg DM; AX + CU) for 90 days of study period. The result showed that BW and dry matter intake (DMI) were significantly higher (P < 0.05) in AX + CU than that in other groups. The average daily gain (ADG) and feed conversion efficiency (FCE) were statistically higher (P < 0.05) in treatments than the values observed in CON. The feed conversion ratio (FCR) was reported significantly lower (P < 0.05) in the AX + CU group followed by AX, CU, and CON groups. The total leukocytes count (TLC), lymphocytes, and total immunoglobulin (TIG) were statistically higher (P < 0.05) in AX + CU groups than that found in other groups. However, neutrophil % decreased (P < 0.05) in the AX + CU group than its level in other groups. Superoxide dismutase (SOD), catalase (CAT), and total antioxidant (TAA) levels were observed higher (P < 0.05) in treatments supplemented with ASTX, Cu, or both than CON group. Thiobarbituric acid reactive substance (TBARS) concentration was lower (P < 0.05) in treatments than its level found in the CON group. Glucose level was higher (P < 0.05); however, non-esterifies fatty acid (NEFA) was lower (P < 0.05) in AX + CU than that in others groups. The level of cholesterol (CH), HDL cholesterol (HDL-CH), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were reported lower (P < 0.05) in the AX + CU group followed by CU, AX, and CON groups. The copper (Cu) level was higher (P < 0.05) in CU and AX + CU than AX and CON groups. The result of the present study indicated that the supplementation of ASTX, Cu alone, or their combination improved the growth, immunity, antioxidant status, and liver function of growing heifers.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study.

OBJECTIVE: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life. DESIGN: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis. SETTING: Community-based integrated health care delivery system. PARTICIPANTS: Participants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ADL difficulties at baseline and accumulation during follow-up. RESULTS: TBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. CONCLUSIONS: Further investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted.

Biomedical potential of Anabaena variabilis NCCU-441 based Selenium nanoparticles and their comparison with commercial nanoparticles.

Selenium nanoparticles (SeNPs) are gaining importance in the field of medicines due to their high surface area and unique properties than their other forms of selenium. In this study, biogenic selenium nanoparticles (B-SeNPs) were synthesized using cyanobacteria and their bioactivities (antioxidant, antimicrobial, anticancer and biocompatibility) were determined for comparison with commercially available chemically synthesized selenium nanoparticles (C-SeNPs). Color change of reaction mixture from sky blue to orange-red indicated the synthesis of biogenic SeNPs (B-SeNPs). UV-Vis spectra of the reaction mixture exhibited peak at 266 nm. During optimization, 30 °C of temperature, 24 h of time and 1:2 concentration ratio of sodium selenite and cell extract represented the best condition for SeNPs synthesis. Various functional groups and biochemical compounds present in the aqueous extract of Anabaena variabilis NCCU-441, which may have possibly influenced the reduction process of SeNPs were identified by FT-IR spectrum and GC-MS. The synthesized cyanobacterial SeNPs were orange red in color, spherical in shape, 10.8 nm in size and amorphous in nature. The B-SeNPs showed better anti-oxidant (DPPH, FRAP, SOR and ABTS assays), anti-microbial (antibacterial and antifungal) and anti-cancer activitities along with its biocompatibility in comparison to C-SeNPs suggesting higher probability of their biomedical application.

A rapid and non-destructive ATR-FTIR spectroscopy method supported by chemometrics for discriminating between facial creams and the classification into herbal and non-herbal brands.

Facial creams are considered to be essential beauty items and are used by both females and males on an everyday basis. These can be encountered as an evidentiary material in criminal investigations, particularly in cases related to sexual and physical assaults against women. These are found in trace amounts and therefore their analysis is difficult and also, it must be through non-destructive methods. In the present work ATR-FTIR spectroscopy was employed for the discrimination of 57 samples of face creams out of which 31 were non-herbal and 26 were from herbal category. Visual analysis of the obtained Spectra was done for discrimination purposes but the method was prone to human error and laborious too. The spectroscopic results were analyzed with PCA (Principal Component Analysis) and PLS-DA (Partial least square discriminant analysis) methods. A segregation of samples was seen in the PCA plots to some extent. The class separation and prediction of the samples was performed using PLS-DA method. A good classification was achieved between herbal and non-herbal samples using PLS-DA method. Further, validation of the model was also performed by testing 10 unknown samples.

Neural tube defects: Different types and brief review of neurulation process and its clinical implication.

Neural Tube Defects are the most typical congenital malformations, with almost 300,000 cases annually worldwide. The incidence varies amongst geographical ranges from 0.2 to up to 11 per 1000 live births. In India, incidence is reportedly higher in north than south and can be attributable to diet and genetic variances. Etiology is multifactorial. Severe forms of whitethorn are allied with syndromes. Primary neurulation and secondary neurulation are the most crucial steps in the formation and closure of the neural tube; any interruption can lead to mild to severe NTDs depending on the level of insult during embryogenesis. Various molecular and cellular events take place simultaneously for neural tube bending and closure of the neural tube. Neurological deficit in the newborn is contingent on the level of defect and severity of the structures affected. Survival of the newborn also depends on the severity of the lesion. Folic acid supplementation in all prospective mothers, preferably 4 weeks before conception and at least 12 weeks after conception, can prevent NTDs in folic responsive groups. But there is a significant number of other causes leading to neural tube defects apart from folic acid. Hydrocephalus is the commonest abnormality allied with NTDs in syndromic cases. Conclusion: NTDs are a frequent cause of stillbirths, infant mortality, and palsies in children. There are various reasons for NTDs, but the process of neurulation points towards some factors of NTC, which can be taken care of to lessen the burden of NTDs.

The role of Yoga in working from home during the COVID-19 global lockdown.

BACKGROUND: The COVID-19 pandemic has become a major cause of stress and anxiety worldwide. Due to the global lockdown, work, employment, businesses and the economic climate have been severely affected. It has generated stress among people from all sections of society, especially to workers who have been assigned to cater to healthcare service or those constrained to secure daily essential items. It is widely perceived that elderly or those affected by diabetes, hypertension and other cardiovascular diseases are prone to COVID-19. As per an ongoing survey, the initial data shows that the above-mentioned anxiety and stress cause insomnia, and has the considerable potential to weaken the immune system, the sole protection against the virus. OBJECTIVE: This study focuses on the need of Yoga practice at work places and at home during the global lockdown due to the COVID-19 pandemic. METHODS: Literature was searched using PubMed and Google Scholar for COVID-19-related stress and anxiety at work and society due to the worldwide lockdown. The predisposing comorbidities, viral mechanism of action and treatment regimen were also searched. Yoga-based intervention studies and online programs were also searched. RESULTS: As the lockdown cannot last forever and workplaces will have to be functional soon, there is an increased possibility of recurrent infection. Therefore, Yoga can provide the necessary tool for risk reduction, amelioration of stress and anxiety and strengthening of the immune function. The online platforms provide a good media for Yoga training at work places and homes. CONCLUSION: Due to social distancing norms, the availability of Yoga trainers has become restricted. Yoga practice is actively sought to achieve reduced anxiety and stress so that improved sleep may positively impact immunity. As a consequence, there is a spurt in social media, catering to daily online Yoga sessions which apparently prove useful in providing accessible means to achieve mental as well as physical well-being.

Anti-Pituitary and Anti-Hypothalamus Autoantibody Associations with Inflammation and Persistent Hypogonadotropic Hypogonadism in Men with Traumatic Brain Injury.

Traumatic brain injury (TBI) and can lead to persistent hypogonadotropic hypogonadism (PHH) and poor outcomes. We hypothesized that autoimmune and inflammatory mechanisms contribute to PHH pathogenesis. Men with moderate-to-severe TBI (n = 143) were compared with healthy men (n = 39). The TBI group provided blood samples 1-12 months post-injury (n = 1225). TBI and healthy control (n = 39) samples were assayed for testosterone (T) and luteinizing hormone (LH) to adjudicate PHH status. TBI samples 1-6 months post-injury and control samples were assayed for immunoglobulin M (IgM)/immunoglobulin G (IgG) anti-pituitary autoantibodies (APA) and anti-hypothalamus autoantibodies (AHA). Tissue antigen specificity for APA and AHA was confirmed via immunohistochemistry (IHC). IgM and IgG autoantibodies for glial fibrillary acid protein (GFAP) (AGA) were evaluated to gauge APA and AHA production as a generalized autoimmune response to TBI and to evaluate the specificity of APA and AHA to PHH status. An inflammatory marker panel was used to assess relationships to autoantibody profiles and PHH status. Fifty-one men with TBI (36%) had PHH. An age-related decline in T levels by both TBI and PHH status were observed. Injured men had higher APA IgM, APA IgG, AHA IgM, AHA IgG, AGA IgM, and AGA IgG than controls (p < 0.0001 all comparisons). However, only APA IgM (p = 0.03) and AHA IgM (p = 0.03) levels were lower in the PHH than in the non-PHH group in multivariate analysis. There were no differences in IgG levels by PHH status. Multiple inflammatory markers were positively correlated with IgM autoantibody production. PHH was associated with higher soluble tumor-necrosis-factor receptors I/II, (sTNFRI, sTNFRII), regulated on activation, normal T-cell expressed and secreted (RANTES) and soluble interleukin-2-receptor-alpha (sIL-2Rα) levels. Higher IgM APA, and AHA, but not AGA, in the absence of PHH may suggest a beneficial or reparative role for neuroendocrine tissue-specific IgM autoantibody production against PHH development post-TBI.

Naringenin Suppresses Chemically Induced Skin Cancer in Two-Stage Skin Carcinogenesis Mouse Model.

Background: Naringenin, a flavonoid present in citrus fruits has many health promoting activities. It has been reported to protect skin from UV radiation, thermal damage and atopic allergies. Despite many skin protective effects, in vivo effect of naringenin on skin cancer has not been reported so far.Objective: The present work was designed to study the chemo preventive effect of naringenin on chemically induced skin cancer in mice.Methods: Two stage model of skin papillomagenesis, using DMBA plus croton oil, was used to study the effect of naringenin in Swiss albino mice. The chemo preventive effect was evaluated using morphological, histopathological and biochemical features.Results: Oral administration of naringenin reduced the skin papilloma in both pre-treatment as well as post-treatment groups of mice. The number as well as size of papilloma was significantly reduced in the treated groups. Histopathological studies showed that naringenin treatment suppressed papillomagenesis. Biochemical studies further revealed decrease in the activity of glyoxalase-1 enzyme and an increase in carbonyl content. The effect was more pronounced in ant-initiation group.Conclusion: Naringenin exhibited anti-tumor effect in two stage carcinogenesis mouse skin tumor model. This study revealed that consumption of citrus fruits and the naringenin therein may be helpful in suppression of skin cancer.

Pharmacotherapeutics and Molecular Mechanism of Phytochemicals in Alleviating Hormone-Responsive Breast Cancer.

Breast cancer (BC) is the leading cause of death among women worldwide devoid of effective treatment. It is therefore important to develop agents that can reverse, reduce, or slow the growth of BC. The use of natural products as chemopreventive agents provides enormous advantages. The aim of the current investigation is to determine the efficacy of the phytochemicals against BC along with the approved drugs to screen the most desirable and effective phytocompound. In the current study, 36 phytochemicals have been evaluated against aromatase to identify the potential candidate drug along with the approved drugs employing the Cdocker module accessible on the Discovery Studio (DS) v4.5 and thereafter analysing the stability of the protein ligand complex using GROningen MAchine for Chemical Simulations v5.0.6 (GROMACS). Additionally, these compounds were assessed for the inhibitory features employing the structure-based pharmacophore (SBP). The Cdocker protocol available with the DS has computed higher dock scores for the phytochemicals complemented by lower binding energies. The top-ranked compounds that have anchored with key residues located at the binding pocket of the protein were subjected to molecular dynamics (MD) simulations employing GROMACS. The resultant findings reveal the stability of the protein backbone and further guide to comprehend on the involvement of key residues Phe134, Val370, and Met374 that mechanistically inhibit BC. Among 36 compounds, curcumin, capsaicin, rosmarinic acid, and 6-shogaol have emerged as promising phytochemicals conferred with the highest Cdocker interaction energy, key residue interactions, stable MD results than reference drugs, and imbibing the key inhibitory features. Taken together, the current study illuminates the use of natural compounds as potential drugs against BC. Additionally, these compounds could also serve as scaffolds in designing and development of new drugs.

Ginger (Zingiber officinale) phytochemicals-gingerenone-A and shogaol inhibit SaHPPK: molecular docking, molecular dynamics simulations and in vitro approaches.

BACKGROUND: Antibiotic resistance is a defense mechanism, harbored by pathogens to survive under unfavorable conditions. Among several antibiotic resistant microbial consortium, Staphylococcus aureus is one of the most havoc microorganisms. Staphylococcus aureus encodes a unique enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (SaHPPK), against which, none of existing antibiotics have been reported. METHODS: Computational approaches have been instrumental in designing and discovering new drugs for several diseases. The present study highlights the impact of ginger phytochemicals on Staphylococcus aureus SaHPPK. Herein, we have retrieved eight ginger phytochemicals from published literature and investigated their inhibitory interactions with SaHPPK. To authenticate our work, the investigation proceeds considering the known antibiotics alongside the phytochemicals. Molecular docking was performed employing GOLD and CDOCKER. The compounds with the highest dock score from both the docking programmes were tested for their inhibitory capability in vitro. The binding conformations that were seated within the binding pocket showing strong interactions with the active sites residues rendered by highest dock score were forwarded towards the molecular dynamic (MD) simulation analysis. RESULTS: Based on molecular dock scores, molecular interaction with catalytic active residues and MD simulations studies, two ginger phytochemicals, gingerenone-A and shogaol have been proposed as candidate inhibitors against Staphylococcus aureus. They have demonstrated higher dock scores than the known antibiotics and have represented interactions with the key residues within the active site. Furthermore, these compounds have rendered considerable inhibitory activity when tested in vitro. Additionally, their superiority was corroborated by stable MD results conducted for 100 ns employing GROMACS package. CONCLUSIONS: Finally, we suggest that gingerenone-A and shogaol may either be potential SaHPPK inhibitors or can be used as fundamental platforms for novel SaHPPK inhibitor development.

Quinoline-based Protein-protein Interaction Inhibitors of LEDGF/p75 and HIV Integrase: An In Silico Study.

The failure of the Integrase Strand Transfer Inhibitors (INSTIs) due to the mutations occurring at the catalytic site of HIV integrase (IN) has led to the design of allosteric integrase inhibitors (ALLINIs). Lens epithelium derived growth factor (LEDGF/p75) is the host cellular cofactor which helps chaining IN to the chromatin. The protein-protein interactions (PPIs) were observed at the allosteric site (LEDGF/p75 binding domain) between LEDGF/p75 of the host cell and IN of virus. In recent years, many small molecules such as CX04328, CHIBA-3053 and CHI-104 have been reported as LEDGF/p75-IN interaction inhibitors (LEDGINs). LEDGINs have emerged as promising therapeutics to halt the PPIs by binding at the interface of both the proteins. In the present work, we correlated the docking scores for the reported LEDGINs containing quinoline scaffold with the in vitro biological data. The hierarchal clustering method was used to divide the compounds into test and training set. The robustness of the generated model was validated by q2 and r2 for the predicted set of compounds. The generated model between the docking score and biological data was assessed to predict the activity of the hits (quinoline scaffold) obtained from virtual screening of LEDGINs providing their structureactivity relationships to aim for the generation of potent agents.

Role of 2-Dimensional Autocorrelation Descriptors in Predicting Antimalarial Activity of Artemisinin and its Aanalogues: A QSAR Study.

BACKGROUND: Malaria, one of the World's biggest billers' is on the schedule for biomedical research and public health policies. The introduction of the artemisinin, a Chinese traditional drug from Artemisia annua is a revolution in the treatment of malaria. Artemisinin-based combination treatment (ACT) is considered to be the best strategy for uncomplicated Falciparum malaria. The presence of 1,2,4-trioxane system in artemisinin is responsible for its antimalarial activity. METHODS: In this study, twenty-nine analogues of artemisinin were taken into account for QSAR studies along with artemisinin. The most active analogue of artemisinin 21 was energy minimized. All the structures were prepared from the active conformer 21 and energy was minimized to the stable state using MMFF94 force field using ChemBioDraw-12. Genetic Algorithm is used to decide the descriptors best required for the model generation. The test set and training set division were done by using hierarchal clustering module available with NCSS statistical software. RESULTS AND CONCLUSION: The antimalarial activity of the artemisinin and its substituted analogues has been analyzed through the multiple linear regression (MLR) using various physiochemical and structural descriptors obtained from PADEL software. The models were prepared using the Sigma Plot version 11. The calculated 2D autocorrelation descriptors and the MLR model suggest that artemisinin and its analogues hold the scope in the optimization of antimalarial activity.

Integration of Andrographis paniculata as Potential Medicinal Plant in Chir Pine (Pinus roxburghii Sarg.) Plantation of North-Western Himalaya.

The integration of Andrographis paniculata under Pinus roxburghii (Chir pine) plantation has been studied to evaluate the growth and yield for its economic viability and conservation. It was grown on three topographical aspects, namely, northern, north-western, and western, at a spacing of 30 cm × 30 cm, followed by three tillage depths, namely, minimum (0 cm), medium (up to 10 cm), and deep (up to 15 cm) tillage. The growth parameters, namely, plant height and number of branches per plant, were recorded as significantly higher on western aspect and lowest on northern aspect except for leaf area index which was found nonsignificant. However under all tillage practices all the growth parameters in both understorey and open conditions were found to be nonsignificant except for plant height which was found to be significantly highest under deep tillage and lowest under minimum tillage. The study of net returns for Andrographis paniculata revealed that it had positive average annual returns even in understorey conditions which indicate its possible economic viability under integration of Chir pine plantations. Hence net returns can be enhanced by integrating Andrographis paniculata and this silvimedicinal system can be suggested which will help utilizing an unutilized part of land and increase total productivity from such lands besides conservation of the A. paniculata in situ.

Comparative Evaluation of Dexmedetomidine and Magnesium Sulphate on Propofol Consumption, Haemodynamics and Postoperative Recovery in Spine Surgery: A Prospective, Randomized, Placebo Controlled, Double-blind Study.

PURPOSE: Dexmedetomidine and magnesium sulfate have been used in anesthesia as adjuvant to provide hemodynamic stability and anesthetic agents sparing effect. We compared these effects of dexmedetomidine and magnesium sulfate in spine surgeries. METHODS: Ninety patients were randomly assigned to three groups. Group D received dexmedetomidine loading dose 1 µg/kg over a period of 15 minutes and maintenance 0.5 µg/kg/h throughout the surgery. Group M received magnesium sulfate loading dose 50 mg/kg over a period of 15 minutes and maintenance 15 mg/kg/h throughout the surgery. Group C received same volume of normal saline. Heart rate (HR) and blood pressure values were recorded at various intervals. The induction and maintenance doses of anesthetics and recovery parameters were also recorded. RESULTS: Heart rate in group D and group M were significantly decreased (p<0.05) during the whole intraoperative period compared to preoperative values. There was a significant difference in HR values between group C, D and M, during the whole intraoperaive period (p<0.05). Blood pressure values were statistically significantly lower in the group D and group M compared to group C after intubation and all time observations of surgery (p<0.05). Both drugs reduced the anesthetic agent's requirement during surgery. However, the recovery parameters were statistically significant increase with magnesium sulphate compared to dexmedetomidine and control groups. CONCLUSION: Dexmedetomidine is more effective than magnesium sulfate for maintaining the hemodynamic stability in spine surgeries. Both these drugs also reduce the requirements of anesthetic agents. Recovery from dexmedetomidine is as rapid as control group compared to magnesium sulfate.

Toxicophore exploration as a screening technology for drug design and discovery: techniques, scope and limitations.

Toxicity is a common drawback of newly designed chemotherapeutic agents. With the exception of pharmacophore-induced toxicity (lack of selectivity at higher concentrations of a drug), the toxicity due to chemotherapeutic agents is based on the toxicophore moiety present in the drug. To date, methodologies implemented to determine toxicophores may be broadly classified into biological, bioanalytical and computational approaches. The biological approach involves analysis of bioactivated metabolites, whereas the computational approach involves a QSAR-based method, mapping techniques, an inverse docking technique and a few toxicophore identification/estimation tools. Being one of the major steps in drug discovery process, toxicophore identification has proven to be an essential screening step in drug design and development. The paper is first of its kind, attempting to cover and compare different methodologies employed in predicting and determining toxicophores with an emphasis on their scope and limitations. Such information may prove vital in the appropriate selection of methodology and can be used as screening technology by researchers to discover the toxicophoric potentials of their designed and synthesized moieties. Additionally, it can be utilized in the manipulation of molecules containing toxicophores in such a manner that their toxicities might be eliminated or removed.