Molecular Targets of Valeric Acid: A Bioactive Natural Product for Endocrine, Metabolic, and Immunological Disorders.

BACKGROUNDS: Postbiotics produced by gut microbiota have exhibited diverse pharmacological activities. Valeric acid, a postbiotic material produced by gut microbiota and some plant species like valerian, has been explored to have diverse pharmacological activities. METHODS: This narrative review aims to summarise the beneficial role of valeric acid for different health conditions along with its underlying mechanism. In order to get ample scientific evidence, various databases like Science Direct, PubMed, Scopus, Google Scholar and Google were exhaustively explored to collect relevant information. Collected data were arranged and analyzed to reach meaningful a conclusion regarding the bioactivity profiling of valeric acid, its mechanism, and future prospects. RESULTS: Valeric acid belongs to short-chain fatty acids (SCFAs) compounds like acetate, propionate, butyrate, pentanoic (valeric) acid, and hexanoic (caproic) acid. Valeric acid has been identified as one of the potent histone deacetylase (HDAC) inhibitors. In different preclinical in -vitro and in-vivo studies, valeric acid has been found to have anti-cancer, anti-diabetic, antihypertensive, anti-inflammatory, and immunomodulatory activity and affects molecular pathways of different diseases like Alzheimer's, Parkinson's, and epilepsy. CONCLUSION: These findings highlight the role of valeric acid as a potential novel therapeutic agent for endocrine, metabolic and immunity-related health conditions, and it must be tested under clinical conditions to develop as a promising drug.

Carbon offset potential of biochar based straw management under rice- wheat system along Indo-Gangetic Plains of India.

The Paris Agreement goal of a net-zero equation will require decarbonization technologies in agriculture. Agri-waste biochar offers huge potential for carbon abatement in agricultural soils. The present experiment was carried out to compare the effects of residue management, viz., no residue (NR), residue incorporation (RI), and biochar (BC), as well as nitrogen options for emission reduction and carbon capture under the rice-wheat cropping sequence (RWCS) of the Indo-Gangetic Plains (IGP), India. After two cycles of cropping pattern, the analysis revealed that the biochar application (BC) reduces the RWCS's annual CO2 emissions by 18.1 % over residue incorporation (RI), while CH4 and N2O emissions were reduced by 23 % and 20.6 % over RI and 11 % and 29.3 % over no residue (NR), respectively. The application of biochar-based nutrient composites with rice straw biourea (RSBU) at 100 % and 75 % significantly reduced greenhouse gases (CH4 and N2O) compared to commercial urea at 100 %. The global warming potential of cropping systems recorded with BC was 7 % and 19.3 % lower than NR and RI, respectively, while 6-15 % under RSBU over urea 100 %. The annual carbon footprint (CF) under BC and NR decreased by 37.2 % and 30.8 % over RI, respectively. The net CF under residue burning was estimated to be the highest (132.5 Tg CO2-Ce), followed by RI (55.3 Tg CO2-Ce), showing net positive emissions; however, net negative emissions were found under a biochar-based system. The estimated annual carbon offset potential of a complete biochar system over residue burning, incorporation, and partial biochar as calculated was 189, 112, and 92 Tg CO2-Ce yr-1, respectively. A biochar-based approach to managing rice straw had great carbon offset potential through a large drop in greenhouse gas emissions and an improved soil carbon pool under the rice wheat system along the IGP, India.

Tagging Efficiency of 99m Tc-SC Radiolabeled Alternative Gastric Emptying Meals: A Quantitative Study.

Objective The aim of this study was to know the tagging efficiencies of technetium-99m labeled sulfur colloid (99mTc-SC) with different meals. Materials and Methods Egg white sandwiches are the gold standard for gastric-emptying scan (GES); thus, an egg white omelet labeled with 99m Tc-SC is taken as a standard meal. For evaluation, we included four meals, bread and butter, instant oatmeal, idli, and chapatti, and all meals were prepared by labeling them with 99m Tc-SC. After preparation, food articles were chopped with the help of a metal fork and mixed in simulated gastric fluid. Four samples were taken simultaneously from each food article and analyzed for 1 to 4hours after agitation within the centrifuge. The samples were filtered and separated from the sediments and supernatants. We analyzed the activity in each sample before and after filtration. Results The mean values of labeling efficiency in per cent of various meals were obtained. There was no significant difference in labeling stability for egg whites, chapatti, and idli meals labeled with 99m Tc-SC from 1 to 4hours as their p -value (p>0.05) was insignificant. Conclusion Radiolabeled chapatti and idli with 99m Tc-SC show higher labeling stability, while oatmeal and bread and butter samples show relatively low stability. Thus, for GES, chapatti and idli labeled with 99m Tc-SC can be used as alternatives to eggs for vegetarian people or for those allergic to eggs.

Effects of diet on hypertensive disorders during pregnancy: A cross-sectional study from a teaching hospital.

BACKGROUND: Pregnancy is a positive, fulfilling experience for many, but it can put the mother at the risk of suffering ill-health, disability, or even maternal death. The common causes of maternal death include pregnancy-induced hypertension (PIH) or gestational hypertension or hypertensive disorders in pregnancy (HDP), post-partum hemorrhage, and pulmonary embolism. Modifications in lifestyle and diet have been widely advocated as a cost-effective strategy to prevent PIH. OBJECTIVES: To assess the role of dietary factors in PIH attending antenatal care services at a teaching hospital. MATERIALS AND METHODS: Pregnant women who were attending the antenatal clinic who were diagnosed with hypertension in pregnancy and normotensive before the pregnancy were included in the study. As per the protocol, informed written consent, demographic details with clinical data were obtained from the patients. A total of 225 antenatal cases having hypertension in pregnancy were included in our study. RESULTS: Majority of the study subjects (81.8%) were taking mixed diets, 50.2% consumed additional salt in their diet, the intake history of visible fat was given by 25.3% and 96.4% consumed tea while 52.9% had a history of consuming junk food. Among the 41 vegetarian study subjects with hypertension in pregnancy, the maximum subjects (73.1%) had preeclampsia followed by gestational hypertension in 23.6% the subjects. The relation between the type of diet and hypertension in pregnancy was found to be statistically insignificant. The relation between visible fat consumption and hypertension in pregnancy was found to be statistically significant. DISCUSSION: The association of dietary factors with HDP could be explained by several factors. One being the high-calorie intake by women with known HDP and those without HDP. The imbalance between the energy intake and expenditure is a potential risk factor and leads to overweight or obesity. CONCLUSION: The consumption of additional salt in the diet, visible fat, and obesity was found to be associated with HDP in our study.

Optimizing the impact of health and related programmes / policies to address the issue of Childhood Obesity in India----A narrative review.

Non-communicable diseases are already acknowledged as a double burden, and now childhood obesity is putting extra strain on our health system. The current paper aimed to analyze the ongoing health and related programmes/policies in India, and we discussed the existing opportunities in the programmes to address the issue of childhood obesity in India. We searched the "MEDLINE," "PsycINFO," "Scopus," "Web of Science," and "Google Scholar" databases using the following keywords: ("overweight") and ("obesity"), ("childhood obesity"), ("nutritional programmes in India"), ("Health policies in India"), ("malnourished children in India") in combination with each other and in truncated form. All the relevant articles and policy documents (MOHFW, INDIA) available in the public domain were included to support the argument for this narrative review. We found that we have programme gaps like guidelines issues by Food Safety Standards Authority of India to tackle childhood obesity and it has not been strictly implemented due to multiple reasons. School health programme has an opportunity to address the issue of childhood obesity, but at the ground level the outcomes are not very promising. The National Nutrition Mission have only focussed on undernutrition and anemia problem, ignoring the overweight/childhood obesity. Primary care physicians are key players in the treatment of childhood obesity, yet rates of obesity management in the primary care setting are low. National Programme for prevention & Control of Cancer, Diabetes, Cardiovascular Diseases & stroke is dealing with health promotion and prevention, early diagnosis, and management of all ages, except children. Diet provided in Integrated Child Development Scheme is calculated based on calories, not by the quality which is a concern to us. The breastfeeding promotion programme named Mothers Absolute Affection programme has not been implemented with letter and spirit. Other than health programmes, we assume that Ministry of Urban Planning, Foreign Direct Investment policy, Advertisement Council of India and many more sector/policy/programme are indirectly responsible for the increasing burden of childhood obesity in India. Lack of awareness and wrong perception also responsible for the development of childhood obesity. We have multiple National Health Programmes and Policies to address the childhood malnutrition, but are focussing the undernutrition component only, ignoring overnutrition problem in the children, which is emerging as quadruple burden to our health system. Appropriate actions and inclusion of suggestions provided in this study for the improvement of the programmes at the practical level needs to be considered by the policy makers to halt the ever-rising trend of childhood obesity and primary care physicians should play a leadership role.

Colour coded client segmentation (CCCS) public health approach to educate the community to deal with problem of hypertension: A pilot study.

INTRODUCTION: We know that risk communication is equally important as risk identification, which is usually not communicated properly to the patients and resulting in poor outcomes, especially in hypertensive patients. OBJECTIVE: Our study objective was to evolve and test a colour coded client segmentation based public health approach to educate the community to deal with problem of hypertension. METHODOLOGY: This cross-sectional pilot study was done in March 2020 among purposively approached in a primary health centre to 100 people aged above 18 years, among them 41 gave written consent for the study and their demographic information was noted. They were given colour coded cards as per the current blood pressure level and previous history of hypertension. On each colour coded card, specific advice was written for that category. For all the participants, blood pressure and treatment seeking behaviour was noted. For hypertensive patients, adherence to medication and non-pharmacological measures was noted. RESULTS: Mean age of the participants was 46.5 ± 13.06 years. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) of the participants were 135 ± 16.85 mm Hg and 86 ± 11.42 mm Hg, respectively. Among the participants, 10 (24.39%) had a known history of hypertension. Among them, as per the blood pressure levels measured on the day of the study 50% (5) had their blood pressure levels under control. Interestingly 16 (39%) participants were found hypertensive incidentally. DISCUSSION: It is evident from the studies that colour coded approach is used in multiple ways, in multiple settings, for multiple diseases. To our knowledge, little focus has been given for hypertensive disorders in the community level. We merely bother about making their risk profiling, even in the digital age. Sometimes physicians in emergency become puzzled whenever patients collapsed in front of them and we missed the "Golden Hour" for the treatment by searching patients' medical details. CONCLUSION AND RECOMMENDATIONS: The above problem can be solved by risk profiling of chronic patients by colour coded OPD/Health cards.

Colour coding-based client segmentation approach: A neglected yet powerful tool to tackle non communicable diseases in high burden and low resource setting countries- A primary care approach.

Health systems in low- and middle-income countries like India continue to struggle with the overwhelming burden of noncommunicable diseases (NCDs) alongside the coexistence of multiple medical conditions. Such cases are challenging to diagnose and treat, especially in places where electronic health records are not readily available. In such contexts, using colour coding system for recording health conditions may ensure optimal documentation, effective patient-provider communication, adherence to treatment and follow up, quality of health services, and an overall improvement in health systems performance for NCDs. Colour coding is a common tool used in several service industries including public health programmes locally and globally. Despite such promising aspects, colour coding is not widely used for NCDs in health services organizations, which necessitates a translation of evidence from other sectors and the adoption of innovative and evidence-based approaches to promote the use of colour coding for better addressing NCD epidemic.

Identifying the risk factors for the prevention of hypertensive disorders in pregnancy in a tertiary care hospital: A cross-sectional study.

INTRODUCTION: Hypertensive disorders in pregnancy accounts for maternal morbidity and mortality globally. AIM AND OBJECTIVES: We conducted this study to know the demographic profile and risk factors pertaining to lifestyle and behavioral aspects for hypertension among the pregnant women. METHODOLOGY: It was a hospital-based cross-sectional study. During the routine antenatal checkups, those antenatal cases found hypertensive, were included in the study after taking written consent. A semi-structured questionnaire was prepared and pretested before conducting the actual study. Statistical analysis was done by SPSS (version 17) software. Participants' sociodemographic characteristics were described using descriptive statistics. Results are presented using graphs, tables, mean, percentages, standard deviation, frequency, and significance. RESULTS: We observed that most of the study subjects 110 (48.9%) were educated up to secondary level followed by primary level 47 (20.9%) while 25 (11.1%) of the subjects were illiterate. We also found that 113 (50.2%) of the study subjects consumed additional salt in their diet and 57 (25.3%) of the study subjects had a history of intake of visible fat. Among 225 study subjects, 174 (77.3%) did not consume tobacco in any form. Among the 225 study subjects, 142 (60.9%) did not have a family history of hypertension. It was observed that 121 (53.77%) subjects had normal BMI while 16 (7.11%) subjects were underweight while 51 (22.6%) subjects were pre-obese. A total of 32 (14.22%) subjects were obese class 1 followed by 5 (2.22%) subjects who were obese class 2. It was observed that among 225 study subjects, 155 (68.9%) subjects had mild hypertension while 70 (31.1%) subjects had severe hypertension. DISCUSSION: The scarcity of data regarding hypertension in pregnancy in low and middle income countries despite this, a comparatively high prevalence of hypertension in pregnancy was observed due to behavioral risk factors, which is mostly preventable at the primary care level. RECOMMENDATIONS: It is possible to prevent PIH by eliminating behavioral risk factors through education and counseling to the pregnant ladies, at the primary care level by family physicians or primary care physicians which will reduce maternal mortality to a great extent.

A relative assessment of essential oil of Chrysopogon zizanioides and Matricaria chamomilla along with calcium hydroxide and chlorhexidine gel against Enterococcus faecalis in ex vivo root canal models.

OBJECTIVE: The objective of this study was to evaluate the antibacterial efficacy of two doses of vetiver and chamomile essential oils compared with chlorhexidine and calcium hydroxide against Enterococcus faecalis. MATERIALS AND METHODS: The growth inhibition and minimum inhibitory concentration of all tested materials were determined ex vivo following agar diffusion and broth dilution assay procedure. Human maxillary anterior teeth were prepared with protaper rotary files, followed by incubation with standard broth of E. faecalis. A total of 140 teeth were included in the study. These teeth are randomized and equally divided into seven groups and were treated with low (1.25 µl) and high doses (2.5 µl) of essential oils of vetiver and chamomile and calcium hydroxide (0.1/1.0 mL), 2% chlorhexidine (2.5 µl). Microbial sampling of six teeth from each group was done with paper points and Gates-Glidden burs at 1, 7, and 14 days and colony-forming unit (CFU)/mL was determined. RESULTS: There was a significant reduction in mean ± standard deviation of CFU (log10) in vetiver oil high dose (3.32 ± 0.036) and chlorhexidine (3.34 ± 0.030), followed by calcium hydroxide (3.46 ± 0.015) and chamomile oil high dose (3.48 ± 0.20) on day 1. On 7th day, a significant reduction was seen in chlorhexidine (2.74 ± 0.212), chamomile oil (2.81 ± 0.035, low dose and 2.97 ± 0.119, high dose), followed by calcium hydroxide (3.25 ± 0.028). However, on 14th day, it was 2.32 ± 0.088 for chlorhexidine, 2.91 ± 0.029 for chamomile oil high dose, 3.15 ± 0.010 for vetiver oil high dose, and 3.09 ± 0.068 for calcium hydroxide. CONCLUSION: The study showed a good effectiveness of chamomile oils in root canal infection of E. faecalis at different time intervals compared to chlorhexidine and calcium hydroxide vetiver oil did not sustain their activity for a longer duration.

Rutin protects t­butyl hydroperoxide-induced oxidative impairment via modulating the Nrf2 and iNOS activity.

BACKGROUND: Rutin (quercetin-3-O-rutinoside), a flavonoid, is predominantly found in the buckwheat, cranberries, mulberry and citrus fruits. It is used as a restorative in the preparation of herbal medicine, multivitamin and known to reduce the fate of heart attack. HYPOTHESIS: We aimed to elucidate whether rutin attenuates oxidative stress and its possible mechanism of action in ameliorating the deleterious effect of t-BHP. We also provide evidence that rutin protects the antioxidant status of erythrocytes and liver via Nrf2 and iNOS pathway from oxidative stress. STUDY DESIGN/METHOD: Human erythrocytes and mice liver were used for the evaluation of rutin's effect against t-BHP induced oxidative stress. The non-enzymatic (GSH, MDA, -CO, -SH) and enzymatic stress markers (SOD, CAT, GPx, GR and GST) were estimated by the colorimetric method. The level of Nrf2, iNOS, liver marker enzymes, triglycerides, cholesterol, HDL-cholesterol, albumin, BUN was measured using ELISA kits. Reactive oxygen species (ROS) was quantified using flow cytometry and fluorometry. RT-PCR was used for the quantification of Nrf2 and iNOS expression levels in the liver tissue of mice. In silico studies were done through receptor-ligand binding interaction. RESULTS: Pre-treatment with the rutin ameliorated the toxic effect of t-BHP by modulating the basal level of GSH, -SH, MDA and -CO significantly (p < 0.01) with respect to untreated control. Rutin also protected the erythrocytes against the t-BHP-induced oxidative stress as evidenced by augmented activity of antioxidant enzymes (CAT, SOD, GPX, GR and GST). Furthermore, at the highest tested concentration (16.3 µM), it protected the morphology of the erythrocytes by decreasing the ROS level (p < 0.01). In addition, the lower MEF values of rutin (0.520 ±â€¯0.005) alone or along with t-BHP (0.630 ±â€¯0.021) indicated its non-toxic and protective behavior. The qPCR analyses revealed that t-BHP potently up-regulates the iNOS and down regulate the Nrf2 expression which was ameliorated with rutin treatment in a dose-dependent manner like silymarin. CONCLUSION: Our findings demonstrate that rutin potentiates its beneficial aspect by displaying a profound role in iNOS-Nrf2 signaling pathway. Accordingly, it may be concluded that the dietary factors wherein rutin is an ingredient could be helpful in the maintenance of the intracellular redox-homeostasis and thus may be effective against oxidative stress related secondary complications.

Fraxetin and ethyl acetate extract from Lawsonia inermis L. ameliorate oxidative stress in P. berghei infected mice by augmenting antioxidant defence system.

BACKGROUND: Lawsonia inermis L. is a well-documented plant for cosmetic as well as medicinal properties. It is used by local communities in India and Nigeria for the treatment of many parasitic diseases, including malaria. HYPOTHESIS/PURPOSE: Earlier studies on the plant's antiplasmodial activity were not assigned to any phytochemical with no quality assurance data. In this report, a recent chemically characterized extract and it's major constituent were investigated for in vitro antiplasmodial activity on chloroquine sensitive NF-54 strain. Furtherly, the potent extract and this constituent were assessed in vivo in Plasmodium berghei infected mice. The bioactive phytochemical and enriched extract were also monitored against various oxidative stress parameters. STUDY DESIGN/METHOD: The extract characterization was done by the quantitative analysis of eight phytochemicals using gradient reverse phase HPLC method. In vitro antiplasmodial activity was evaluated on chloroquine sensitive NF-54 strain by the determination of pfLDH activity. In vivo activity of the most potent extract and constituent were evaluated in P. berghei infected mice upon oral administration. The estimation of oxidative stress was done by monitoring various enzymatic and non-enzymatic parameters. RESULTS: The ethyl acetate extract of leaves (IC50 9.00 ±â€¯0.68 µg/ml) and fraxetin (IC50 19.21 ±â€¯1.04 µM) were the most effective in in vitro assays therefore selected for in vivo tests. The administration of the ethyl acetate extract of leaves and fraxetin to the infected mice resulted in significant (p < .05) suppression of parasitaemia as evidenced by a 70.44 ±â€¯2.58% to 78.77 ±â€¯3.43% reduction compared to non-infected group. In addition, a two-fold increase in mean survival time, a significant (p < .05) reduction in lipid peroxidation and an elevation in glutathione, catalase and superoxide dismutase were also observed in treated mice. The post-infection treatment also led to an augmentation of endogenous antioxidant enzymes (GST, GR, GPx) with respect to the infected control. A significant (p < .05) elevation in serum Nrf2-antioxidant response element level responsible for the activation of endogenous enzymes was also observed. CONCLUSION: It was evident from the experiments that ethyl acetate extract of L. inermis and fraxetin were able to suppress the oxidative damage by augmenting endogenous antioxidant system and thus ameliorated the plasmodium infection in mice.

Label-free, high-throughput holographic screening and enumeration of tumor cells in blood.

We introduce inline digital holographic microscopy (in-line DHM) as a label-free technique for detecting tumor cells in blood. The optimized DHM platform fingerprints every cell flowing through a microchannel at 10 000 cells per second, based on three features - size, maximum intensity and mean intensity. To identify tumor cells in a background of blood cells, we developed robust gating criteria using machine-learning approaches. We established classifiers from the features extracted from 100 000-cell training sets consisting of red blood cells, peripheral blood mononuclear cells and tumor cell lines. The optimized classifier was then applied to targeted features of a single cell in a mixed cell population to make quantitative cell-type predictions. We tested our classification system with tumor cells spiked at different levels into a background of lysed blood that contained predominantly peripheral blood mononuclear cells. Results show that our holographic screening method can readily detect as few as 10 tumor cells per mL, and can identify tumor cells at a false positive rate of at most 0.001%. This purely optical approach obviates the need for antibody labeling and allows large volumes of sample to be quickly processed. Moreover, our in-line DHM approach can be combined with existing circulation tumor cell enrichment strategies, making it a promising tool for label-free analysis of liquid-biopsy samples.

Antiproliferative and antimicrobial efficacy of the compounds isolated from the roots of Oenothera biennis L.

BACKGROUND: Oenothera biennis L., commonly known as evening primrose, harbours the flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of biological activity, such as antitumour, anti-arthritic and anti-inflammatory effects. In addition to the previous reports from aerial parts of this plant, studies related to antiproliferative or antimicrobial activity from the roots are warranted. OBJECTIVE: To investigate antiproliferative and antimicrobial activity of compounds/mixture (1-8) isolated and characterized from the roots of O. biennis L. A possible mechanism of antiproliferative activity was also studied by targeting ornithine decarboxylase (ODC) and cathepsin D (CATD). STUDY DESIGN: Antiproliferative efficacy of the compounds/mixture was examined in selected cancer cell lines along with their probable mechanism of action. The antimicrobial activity was also studied against selected microbes (bacteria and fungi). METHODS: Antiproliferative potential was evaluated by MTT assay against selected cell lines. The mechanism of action was studied spectrophotometrically by targeting ODC and CATD using both an in-vitro and an in-silico approach. The antimicrobial efficiency was analysed using the disc diffusion and broth dilution methods. KEY FINDINGS: Oenotheralanosterol B (3) and the mixture of oenotheralanosterol A and oenotheralanosterol B (4) exhibited antiproliferative activity against breast, hepatic, prostate and leukaemia cancer cell lines as well as in mouse macrophages (IC50 8.35-49.69 µg/ml). Oenotheralanosterol B (3) and the mixture of oenotheralanosterol A and oenotheralanosterol B (4) displayed a strong molecular interaction with succinate dehydrogenase (binding energy -6.23 and -6.84 kcal/mol and Ki 27.03 and 9.6 µm, respectively). Oenotheralanosterol A (1), oenotheralanosterol B (3) and mixture of oenotheralanosterol A and oenotheralanosterol B (4) potently inhibited the ODC activity with IC50 ranging from 4.65 ± 0.35 to 19.06 ± 4.16 µg/ml and also showed a strong interaction with ODC (BE -4.17 to -4.46 kcal/mol). Oenotheralanosterol A (1), cetoleilyl diglucoside (2), oenotheralanosterol B (3), dihydroxyprenylxanthone acetylated (6) and dihydroxyprenylxanthone (7) inhibited CATD activity (IC50 3.95 ± 0.49 to 24.35 ± 2.89 µg/ml). The in-silico molecular interaction analysis of compounds with CATD revealed the non-specific interaction. A moderate antimicrobial activity was observed against selected microbes with a growth inhibition ranging from 6 to 14 mm and minimum inhibitory concentration between 125 and 500 µg/ml. Oenotheralanosterol B (3) and dihydroxyprenylxanthone acetylated (6) exhibited better antimicrobial activity with an MIC range from 62.50 to 500 µg/ml. CONCLUSION: Oenotheralanosterol B (3) exhibited stronger antiproliferative and antimicrobial potential with respect to the other compounds tested, whereas oenotheralanosterol A (1) was a potent inhibitor of ODC and CATD. Hence, it is suggested that these in-vitro findings could be studied further in vivo for biological activity, safety evaluation and derivatization to enhance potency and efficacy.

Characterization and evaluation of bioactive polyphenolic constituents from Zanthoxylum armatum DC., a traditionally used plant.

Zanthoxylum armatum or Timoor has been used in different traditional system of medicine due to its aromatic properties and also in the treatment of cancer, diarrhea and cholera. In the present investigation, four chemically distinct compounds namely Tambulin (6), Prudomestin (7), Ombuin (8) and 3, 4, 5, 3', 4', 5'-hexahydroxydiphenyl ether (9) have been isolated and quantified from the fruits. To explore the biological activities, we have further studied the antiproliferative, antimicrobial and antioxidant efficacy. Tambulin which was also found in maximum amount (0.125%) in fruits revealed significant antiproliferative activity (IC50 37.96±0.36 to 48.7±0.21µg/mL) against breast, liver, colon and skin cancer cell lines corroborated by resilient binding interaction with SDH (-6.76Kcal/mol) and inhibition constant (Ki: 11.02µM). Hexane and ethyl acetate fraction exhibited moderate antibacterial efficacy (MIC: 250-1000µg/mL) against selected pathogenic microbes while Ombuin displayed broad spectrum antibacterial effect with MIC ranges from 125 to 500µg/mL. Total phenolic content (5.27±0.06 to 46.12±0.40mg/g of gallic acid equivalents), total flavonoids content (6.05±0.24 to 14.46±0.73mg/g of quercetin equivalents), ferric reducing power (42.35±0.85 to 62.52±0.66mg/g of ferrous sulfate equivalents) and percent free radical scavenging activity (59.56±0.38 to 64.85±1.78) were also estimated. Our findings infer that Tambulin exhibited significant antiproliferative activity whereas Ombuin was found to display broad spectrum antibacterial activity which adds one more positive attribute to its traditional usage.

Label-free fingerprinting of tumor cells in bulk flow using inline digital holographic microscopy.

Large-scale and label-free phenotyping of cells holds great promise in medicine, especially in cancer diagnostics and prognosis. Here, we introduce inline digital holography microscopy for volumetric imaging of cells in bulk flow and fingerprinting of flowing tumor cells based on two metrics, in-focus scattered intensity and cell diameter. Using planar distribution of immobilized particles, we identify the optimal recording distance and microscope objective magnification that minimizes the error in measurement of particle position, size and scattered intensity. Using the optimized conditions and the two metrics, we demonstrate the capacity to enumerate and fingerprint more than 100,000 cells. Finally, we highlight the power of our label-free and high throughput technology by characterizing breast tumor cell lines with different metastatic potentials and distinguishing drug resistant ovarian cancer cells from their parental cell line.

Eclipta yellow vein virus enhances chlorophyll destruction, singlet oxygen production and alters endogenous redox status in Andrographis paniculata.

The infection of Eclipta yellow vein virus [EcYVV-IN, Accession No. KC476655], recently reported for the first time, on Andrographis paniculata was studied for redox-mediated alteration mechanism in infected plants. A. paniculata, an important medicinal plant, is used in traditional Indian, Chinese and modern system of medicine. Andrographolide, one of the foremost components of this plant, is known for its varied pharmacological properties. Our investigation provides insight into the effect of virus-induced changes in the singlet oxygen quenching due to the alteration in pigment content (chlorophyll and carotenoids) as well as activation of plant secondary metabolism along with defense activation leading to changes in enzymatic and non-enzymatic redox status. Due to infection, a reduction in carotenoid content was observed which leads to reduced quenching of singlet oxygen. An increased level of enzymatic (SOD and APX) and non-enzymatic antioxidant (DPPH, FRAP, RP, NO, TAC and TP) activities were also observed in virus-infected plants with a positive correlation (>0.9). However, CAT activity was diminished which could be either due to its proteolytic degradation or inactivation by superoxide anions (O(2-.)), NO or peroxynitrite radicals. A significant (p < 0.05) increase in total phenolic content was observed in the infected plants while no considerable difference was seen in the total flavonoid content. Our results highlighted the alteration in redox status caused by virus-induced biotic stress on the plants and could be useful for understanding the after effects of viral infection This study could also be helpful in developing biomimetic methods for improving the production of secondary metabolites of pharmaceutical importance.

Effect of 3 Different Doses of Intrathecal Dexmedetomidine (2.5µg, 5µg, and 10 µg) on Subarachnoid Block Characteristics: A Prospective Randomized Double Blind Dose-Response Trial.

BACKGROUND: The extended analgesic efficacy of intrathecal dexmedetomidine (ITD) has been investigated in a few clinical trials; however, there is a lack of conclusive evidence upon its ideal dosage. OBJECTIVES: To elucidate the dose-response relationship between ITD and subarachnoid block characteristics, particularly the duration of analgesia and differential analgesia (DA: defined as time difference from the offset of motor blockade to the first analgesic requirement on numerical rating scale = 4.0). STUDY DESIGN: Prospective, randomized double blind active control trial. SETTING: Medical college teaching hospital. METHODS: Ninety adult (18 - 60 years) patients undergoing elective lower abdominal and lower limb surgeries were randomized into 3 groups to receive intrathecal 0.5% bupivacaine 3 mL with 2.5 µg (group BD2.5), 5µg (group BD5), or 10 µg (group BD10) dexmedetomidine in 0.5 mL normal saline. The 2 segment sensory regression times (TSSRT), duration of motor blockade analgesia, DA, and perioperative adverse effects were assessed. The primary outcome was duration of analgesia and DA. STATISTICS: ANOVA, Kruskal Wallis test, Chi-square (x2), and Fisher's exact test, significance: P < 0.05. RESULTS: The onset of sensory block was significantly earlier in group BD10 compared with group BD5 (P = 0.035) and BD2.5 (P = 0.010) while the onset of motor block was significantly earlier in group BD10 compared with BD2.5 (P = 0.020). There was a significant and dose-dependent prolongation of the duration of sensory block (127.50, 149.17, and 187.50 minutes; P < 0.001), motor block (258.50, 331, and 365 minutes; P < 0.001), analgesia (306.17, 396.50, and 512 minutes; P < 0.001), and DA (47.67, 65.50, and147 minutes; P < 0.001) with escalating doses of ITD, respectively. Group BD10 required significantly fewer rescue analgesics compared with other 2 groups (P = 0.001). Except for mild sedation which was significantly higher in group BD10; all the groups were comparable with respect to hemodynamic and other adverse effects. LIMITATIONS: Lack of placebo group, exclusion of higher doses (15µg) of ITD, and short duration of postoperative follow-up. CONCLUSIONS: The addition of 10 µg compared with 2.5 µg or 5µg ITD to 0.5% hyperbaric bupivacaine is associated with significantly earlier onset of sensory and motor block as well as prolonged duration of sensory block, motor block, analgesia, and DA with a comparable adverse effect profile.

Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology.

PURPOSE: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO). METHODOLOGY: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37 °C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains. RESULTS AND DISCUSSION: Optimized NE had particle size and zeta potential of 16.23 ± 0.411 nm and 36.11 ± 1.234 mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57 ± 0.05 ) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58 µL/cm(2)) and flux value (JSS) of 7.96 µL cm(2)/h through skin in 10 h. Viscosity and texture parameters, firmness (9.3 ± 0.08 g), spreadability (2.26 ± 0.06 mJ), extrudability (61.6 ± 0.05 mJ), and adhesiveness (8.66 ± 0.08 g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d. CONCLUSION: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.

Advances in Boerhaavia diffusa hairy root technology: a valuable pursuit for identifying strain sensitivity and up-scaling factors to refine metabolite yield and bioactivity potentials.

The present study reports the Agrobacterium rhizogenes-mediated hairy root induction in of an ethno-medicinally significant herb-Boerhaavia diffusa L., for elucidating the underlying competence regarding its biosynthetic (i.e. boeravinone B and eupalitin) and bioactivity (antibacterial, antioxidant and anti-inflammatory) potentials. Host plant-specific receptiveness towards A. rhizogenes strains and disparity in compatibility threshold of leaf and nodal explants were evident. Only leaf explants responded, attaining hairy root induction with the ATCC 15834 followed by A4 and SA79 strains in reducing order of transformation efficiency. The growth behaviours differed amongst independent rhizoclones, and two clones of A4 (RBH) and ATCC 15834 (RBT8) origin demonstrated higher growth potentials. Polymerase chain reaction amplification of rol genes confirmed their transformed nature. Optimization of the appropriate solvent and reverse phase high-performance liquid chromatography parameters relating to the targeted metabolite production in the selected RBH and RBT8 clones revealed higher accumulation of eupalitin with the RBH clone having the best result of 1.44 times greater yield over the control root. Compared to the selected rhizoclones, the control roots however showed higher boeravinone B content. Devising a modified "stirred-tank" reactor through equipping with marine impellers and ring spargers facilitated high-density RBH root biomass yield with 6.1-fold and 1.15-fold yield increment of the boeravinone B and eupalitin respectively compared to shake-flask cultures. Considering the control roots, the RBH clone revealed analogous antioxidant/antibacterial activities with improved anti-inflammatory potential. The hairy root mediated higher production of boeravinone B and eupalitin could be achieved for the first time in bioreactor.

Cisplatin Induced Renal Insufficiency Measured by Glomerular Filtration Rate with 99mTc-DTPA and by using Serum Creatinine based Formulae: A Prospective Study.

INTRODUCTION: Cisplatin also known as Cis-Diammine-Dichloroplatinum (CDDP) is a chemotherapeutic alkylating nephrotoxic agent. Thus, it is necessary to know if renal function is normal before starting chemotherapy. Glomerular Filtration Rate (GFR) can be assessed directly by using a radiopharmaceutical (dGFR). Estimated GFR (eGFR) method use, Serum Creatinine (SCR) levels in mathematical formulae such as Cockroft-Gault (CG) and abbreviated. Modified Diet in Renal Disease (aMDRD). The serum creatinine level is a function of GFR but is relatively insensitive for detecting early renal insufficiency. AIM: We aimed to correlate the incidence of Renal Insufficiency (RI) before and one month after completion of chemotherapy treatment by various methods. MATERIALS AND METHODS: In this prospective study, we examined 64 patients with locally advanced head neck and uterine cervix cancers, before and one month after chemotherapy treatment with CDDP. Single agent CDDP was used with dose range between 35mg/m2 as concurrent weekly chemotherapy. RESULTS: Baseline RI was seen in 9.3% of patients by SCR levels, in 21.8% by the dGFR method, in 43.75% by the GFR-CG method and in 25% by the GFR-aMDRD formula. We considered GFR of <60 ml/min and SCR >1.5mg% as RI. After completion of treatment, the median RI was seen in 12.5% by SCR levels, 34.38% by dGFR method, 53.13% by GFR-CG method and 40.63% by GFR-aMDRD formula. None of the methods of GFR estimation showed statistically significant increase in RI one month after CDDP infusion. Only a weak correlation was seen between dGFR and eGFR based on SCR value (p=0.006). CONCLUSION: Baseline RI was detected in 12% more cases when measured by dGFR as compared with SCR level. However, mathematical formulae overestimated baseline RI as compared to dGFR. One month after completion of treatment with CDDP chemotherapy, RI increased in 10%-15% cases as detected by all the four evaluated methods. There is weak correlation between SCR and dGFR thus implicating the importance of dGFR in assessing RI. Thus, despite normal SCR levels, GFR by radioisotope method should also be done as pre-treatment workup for cisplatin based chemotherapy.