A Conjugated Polymer-based Portable Smartphone Platform for Sensitive and Point-of-Care Detection of Monoamine Neurotransmitter┴.

The precise and effective detection of neurotransmitters (NTs) is crucial for clinical investigation of neuronal processes, and timely monitoring of NT-related chronic diseases. However, sensitive detection of specific NT with unprecedented selectivity is highly challenging due to similarities in chemical and electronic structures of various interfering neurochemicals. Herein, an anionic conjugated polyelectrolyte Poly[(9,9-bis(4'-sulfonatobutyl)fluorene-co-alt-1,4-phenylene) sodium], PFPS was rationally designed and synthesized for amplified detection and point-of-care (PoC) determination of monoamine neurotransmitter, serotonin (5-Hydroxy tryptamine or 5-HT, also diagnostic biomarker of carcinoid tumor) in human blood plasma. The PFPS displayed a remarkable sensing response with an exceptionally high fluorescence quenching constant of 1.14 × 105 M-1 and an ultralow detection limit of 0.67 µM or 0.142ppm, much below the clinical range (0.5-1.4 µM). Furthermore, a smartphone-enabled portable platform was constructed for real-time onsite detection of 5-HT by quantification of visual fluorescence response of PFPS into RGB values using a color recognizer android application. The smartphone platform could be readily applied for convenient, non-invasive PoC testing of 5-HT levels in complex biological fluids accurately and is expected to revolutionize clinical diagnosis and personalized health care devices.

Bioactive potential of Lagotis cashmeriana: a study on morphology, phytochemicals, and antioxidant activity.

The present study aimed to investigate the morphological features, phytochemicals, phenolic content, and antioxidant activity in different parts of Lagotis cashmeriana. The morphological features depicted that the plant is 7.9 ± 1.699 cm tall with flowers arranged into an inflorescence. The length of inflorescence was 2.597 ± 0.796 cm. Basal leaves were measuring 2.99 ± 0.58 cm. Besides, the number of basal leaves and inflorescence ranged from 4-9 and 0-4 respectively. Methanolic extract of leaves displayed the highest phenolic content (169.5 µg/mL of GAE), followed by inflorescences (157 µg/mL of GAE). Among aqueous extracts, leaves displayed the highest phenolic content (88.38 µg/mL of GAE), followed by inflorescences (76.95 µg/mL of GAE). The results of antioxidant study revealed that the methanolic extracts of leaves possessed the highest antioxidant potential (180.76 µg/mL of AAE). Interestingly, for each extract, there was a positive correlation between the phenolic content and the antioxidant activity.

Pattern of ß-Diversity and Plant Species Richness along Vertical Gradient in Northwest Himalaya, India.

The structure and distribution patterns of Himalayan vegetation are poorly explored, and research on species composition along the elevation gradient in these mountain ranges is still deficient. The current study was undertaken to analyze the variation and pattern of plant species composition along a vertical gradient in northwestern Himalaya, India. A total of 18 sites were selected along an elevation gradient ranging from 2200 to 3900 m asl positioned at an interval of 100 m. The Renyi diversity profile, non-metric multidimensional scaling based on the Bray-Curtis dissimilarity metric and beta diversity components among the elevation belts were calculated. Furthermore, to study the influence of altitude on species richness and diversity, a generalized additive model was created. Two hundred and ten plant species representing 66 families and 147 genera were recorded. The Renyi diversity profiles show that the lower and mid-altitudes had rich species diversity. The results of the non-metric multidimensional scaling analysis show a considerable variation in the total plant species composition among the studied elevation belts. The observed multiple-site Sorensen dissimilarity index across the studied elevation belts was very high. The contribution of species replacement or the turnover component to the observed dissimilarity was much higher than the nestedness component. Furthermore, the herbaceous and tree richness showed a significant decrease with increase in elevation; however, the richness of shrubs showed a bimodal pattern. The present study increases our understanding of the trends and patterns of species richness along the vertical gradient in the Himalayan region.

Patterns of floristic and functional diversity in two treeline ecotone sites of Kashmir Himalaya.

Globally, the treelines at higher elevations in mountains are reported to be advancing up-slope in response to recent climate warming. However, little is known about the treeline advancement in the Himalaya due to paucity of baseline vegetation data with which to compare, thus making their assessment and monitoring challenging. To fill this knowledge gap, the present study documented floristic and functional diversity of two treeline ecotone sites in Kashmir Himalaya. At each site, we conducted field sampling by laying five 20-m2 plots, with one at the highest limit (T0 plot), two plots below and two above the treeline and two nested subplots of 5-m2 for shrubs and five 1-m2 for herbs in each plot. We recorded 97 plant species belonging to 33 families from the two sites. We observed a considerable difference in species composition and distribution along the treeline ecotone. Majority of the species reported were perennial herbs. We observed a significant association of growth forms with the particular plots along the treeline ecotone. At both the sites, we recorded highest species richness at the T0 plot which was correlated well with the functional traits, thus indicating convergence of floristic and functional diversity at this transition zone. Interestingly, the T0 plot at both the sites showed maximum overlap of species with the plots above and below the treeline. In an era of climate warming, our study provides crucial baseline data that will facilitate assessment and monitoring of the Himalayan treelines.

Conjugated polymer nanoparticles and their nanohybrids as smart photoluminescent and photoresponsive material for biosensing, imaging, and theranostics.

The emergence of conjugated polymers (CPs) has provided a pathway to attain smart multifunctional conjugated polymer nanoparticles (CPNs) with enhanced properties and diverse applications. CPNs based on π-extended CPs exhibit high fluorescence brightness, low cytotoxicity, excellent photostability, reactive oxygen species (ROS) generation ability, high photothermal conversion efficiency (PCE), etc. which endorse them as an excellent theranostic tool. Furthermore, the unique light-harvesting and energy transfer properties of CPNs enables their transformation into smart functional nanohybrids with augmented performance. Owing to such numerous features, simple preparation method and an easy separation process, the CPNs and their hybrids have been constantly rising as a frontrunner in the domain of medicine and much work has been done in the respective research area. This review summarizes the recent progress that has been made in the field of CPNs for biological and biomedical applications with special emphasis on biosensing, imaging, and theranostics. Following an introduction into the field, a first large section provides overview of the conventional as well as recently established synthetic methods for various types of CPNs. Then, the CPNs-based fluorometric assays for biomolecules based on different detection strategies have been described. Later on, examples of CPNs-based probes for imaging, both in vitro and in vivo using cancer cells and animal models have been explored. The next section highlighted the vital theranostic applications of CPNs and corresponding nanohybrids, mainly via imaging-guided photodynamic therapy (PDT), photothermal therapy (PTT) and drug delivery. The last section summarizes the current challenges and gives an outlook on the potential future trends on CPNs as advanced healthcare material.

Substantial shifts in flowering phenology of Sternbergia vernalis in the Himalaya: Supplementing decadal field records with historical and experimental evidences.

In an age of anthropocene, shifting plant phenology is one of the most striking biological indicators of global environmental change. Majority of the studies reporting shifts in plant phenology are available from the North America and Europe and largely scarce from the developing world, including the Himalaya; and studies integrating multiple methodological approaches to investigate the climate-driven phenological shifts are too rare. Here, we report the shifts in spring flowering phenology of model plant species, Sternbergia vernalis in response to the changing climate in Kashmir Himalaya, by integrating decadal field observational records with long-term herbarium and dated-photograph data, and supported with experimental evidences. Our results revealed a significant increasing trend of 0.038, 0.016 and 0.023 °C/year in the annual mean maximum temperature (Tmax), mean minimum temperature (Tmin) and diurnal temperature range (DTR) respectively; but an insignificant decreasing trend in annual precipitation of -1.24 mm/year over the last four decades (1980-2019) in this Himalayan region. The flowering phenology of S. vernalis has significantly advanced by 11.8 days/°C and 27.8 days/°C increase in Tmax and Tmin respectively, indicating that the climate warming has led to substantial shifts in flowering phenology of the model plant species. We also observed a strong association of seasonal Tmax (December-February) and DTR on the early onset of spring flowering, however precipitation had no significant effect on the timing of flowering. The greenhouse experiment results further supported a significant effect of temperature in triggering the phenological shifts, wherein the model plant grown under different temperature treatments flowered 9-20 days earlier compared to the control. Our study showcases the integrated use of multiple methodological approaches for unravelling the long-term phenological shifts in response to climate change, and contributes in filling the knowledge gaps in the phenological research from the developing world in general and the Himalaya in particular.

Medicinal importance of Papra (Podophyllum hexandrum Royle) in Unani System of Medicine.

Podophyllum hexandrum Royle [=Sinopodophyllum hexandrum (Royle) T.S. Ying] is an important, endemic medicinal plant species of Himalaya. It is used in Unani System of Medicine under the name of 'Papra'. The drug was not mentioned in previous literatures, but the first time it introduced in Unani Medicine by a great scholar Hakim Najmul Ghani. He has mentioned its uses and benefits in his classical book Khazainul Advia. In Unani Medicine the plant species has been used to treat various ailments like constipation, fever, jaundice, liver disorders, syphilis, diseases of lymph glands etc. In Kashmir Himalaya it is used to treat various diseases by local medicinemen, but now it is listed in rare drugs. Various pharmacological studies have been done such as antioxidant, antimicrobial, anti-inflammatory, antifungal, radio-protective etc., recently it has also been reported that podophyllotoxin or podophyllin can be used to treat some forms of cancers also.

An anionic conjugated polymer as a multi-action sensor for the sensitive detection of Cu(2+) and PPi, real-time ALP assaying and cell imaging.

A Cu(2+) ensemble polyfluorene derivative, poly[5,5'-(((9H-fluorene-9,9-diyl)bis(hexane-6,1-diyl))bis(oxy))diisophthalate] sodium salt (PFT), displays unprecedented selectivity for PPi (LOD = 2.26 ppb) in aqueous solution as well as in random urine samples at physiological pH vis-a-vis monitoring ALP activity. Furthermore, intracellular imaging of Cu(2+) and PPi in mouse macrophage (J774A.1) and human breast cancer cells (MDA-MB231) was achieved to confirm the viability of PFT in biological systems.

Highly precise detection, discrimination, and removal of anionic surfactants over the full pH range via cationic conjugated polymer: an efficient strategy to facilitate illicit-drug analysis.

A water-soluble cationic conjugated polyelectrolyte (CPE), poly(1,4-bis(6-(1-methylimidazolium)-hexyloxy)-benzene bromide) (PMI) displays extraordinary stability over the full pH range of 1-14 as well as in seawater, brine, urine, and other solutions and carries out efficient detection, discrimination, and removal of moderately dissimilar anionic surfactants (viz., sodium dodecyl benzenesulfonate (SDBS) and sodium dodecyl sulfate (SDS)) at very low levels (31.7 and 17.3 parts per billion (ppb), respectively). PMI formed stable hydrogels in the presence of SDS that remained unaffected by strong acids/bases, heating, ultrasonication, or exposure to light, whereas SDBS formed precipitate with PMI as a result of its different interpolymer cofacial arrangement via Columbic attraction. The complex-forming ability of PMI with SDS and SDBS facilitated their elimination from water or drug-doped urine samples without the use of any organic solvent, chromatographic technique, or solid support. This protocol, the first of its kind for the removal of anionic surfactants at very low concentrations from any type of solution and competitive environments, demonstrates an original application using a CPE. The surfactant-free sample solutions could be precisely analyzed for the presence of illicit drugs by any standard methods. Using PMI, a newly developed CPE, a rapid and practical method for the efficient detection, discrimination, and removal of SDS and SDBS at ppb levels from water and urine, under harsh conditions, and in natural chemical environments is demonstrated.

Phytochemical screening, physicochemical properties, acute toxicity testing and screening of hypoglycaemic activity of extracts of Eremurus himalaicus baker in normoglycaemic Wistar strain albino rats.

In the present study EtOAc, MeOH, and aqueous extracts of Eremurus himalaicus were evaluated for hypoglycaemic effect in normal rats using both oral glucose tolerance test and 14-day oral administration study. Phytochemical and physicochemical screening was also done. In oral glucose tolerance test the aqueous and MeOH extracts of Eremurus himalaicus at a dose level of 500 mg/kg body weight prior to glucose load resulted in a significant fall in blood glucose level within 150 min. of glucose administration. The aqueous extract at a dose level of 250 mg/kg body weight and 500 mg/kg body weight also showed good hypoglycaemic response (P < 0.001); this was followed by MeOH extract at a dose level of 500 mg/kg body weight (P < 0.05), while MeOH extract at dose level of 250 mg/kg body weight and ethyl acetate extract at dose level of 250 mg/kg body weight and 500 mg/kg body weight exhibited insignificant effect. Phytochemical screening of extracts revealed the presence of alkaloids, terpenoids, phenolics, tannins, saponins, cardiac glycosides, and flavonoids. The results indicate that aqueous extract possess significant hypoglycaemic activity in normoglycaemic rats which may be attributed to the above-mentioned chemical constituents.

Scientific Validation of Gentiana kurroo Royle for Anti-Inflammatory and Immunomodulatory Potential.

Gentiana kurroo Royle is a critically endangered medicinal plant species endemic to the northwestern Himalayas. This plant was studied for the immunomodulatory and anti-inflammatory potential. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts were found to be active against inflammation. The methanolic fraction was observed to be the most effective in inhibition of paw edema with the inhibitory potential of 47.62%. In immunomodulation studies the plant extracts showed the immunosuppressant activity. Methanolic fraction was observed to have maximum potential for the suppression of both humoral (57.57% and 54.05%) and cell mediated immunity (65.27% and 75%). From these studies, it can be concluded that the extracts of plant are having anti-inflammatory and immunosuppressant activity. Since in chronic inflammation like arthritis there is the involvement of immune system, this plant may serve as an alternative for the treatment of autoimmune diseases like arthritis.

Evaluation of Artemisia amygdalina D. for Anti-Inflammatory and Immunomodulatory Potential.

Artemisia amygdalina D. is a critically endangered endemic medicinal plant of Kashmir Himalayas. In the current study anti-inflammatory and immunomodulatory activity of the plant was carried out. Carrageenan paw edema model was used to study the potential of the drug in inflammation in Wistar rats. SRBC-specific haemagglutination titre and DTH assays were carried out in Balb/C mice for observing the effect of test drugs on immune system. The plant extracts used as test drugs showed to have anti-inflammatory potential. The methanolic fraction was observed to have the maximum effect on the inhibition of paw edema formation with the inhibitory potential of 42.26%, while in the immunomodulation studies the test drugs were found to have the immunosuppressant activity with methanolic fraction again showing the maximum potential for the suppression of both humoral (55.89% and 47.91%) and cell-mediated immunity (62.27% and 57.21%). The plant in total seems to have the anti-inflammatory potential. The suppression of immune system suggests some mechanistic way by which the inhibition of inflammation takes place. Since, in chronic inflammation like arthritis, there is the involvement of immune system, the plant in that way may serve as an alternative for the treatment of such autoimmune diseases.

Atropa acuminata Royle Ex Lindl. blunts production of pro-inflammatory mediators eicosanoids., leukotrienes, cytokines in vitro and in vivo models of acute inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Atropa acuminata Royle Ex Lindl. has been widely used in folk medicine for several inflammatory disorders such as arthritis, asthma, conjunctivitis, encephalitis, pancreatitis, peritonitis, acute infections and neuroinflammatory disorders. AIM OF THE STUDY: Our aim was to evaluate Atropa acuminata for its anti-inflammatory properties and to delineate its possible mechanism of action on the modulation of the inflammatory mediators. MATERIALS AND METHODS: We investigated the inhibitory action of ethanolic extract of Atropa acuminata (AAEE) on production of NO, TNF-α and IL-1ß in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and also assayed it for COX 1/2 and 5-LOX inhibitory activities. Next AAEE was tested in acute inflammatory animal models., carragenean induced rat paw edema, carragenean induce pleurisy in rats and vascular permeability in mice and the effects on NO, PGE2 and LTB4 production in the pleural fluid and paw exudates were evaluated. In addition the effects on leukocyte migration and exudation and vascular permeability were also observed. RESULTS: Our findings summarized novel anti-inflammatory mechanisms for Atropa acuminata based on dual in vitro cyclooxygenase 1/2/ and 5-Lipoxygenase inhibitory activities and also significant downregulation of nitric oxide (NO) and pro-inflammatory cytokin (TNF-α and Il-1 ß) release in LPS-stimulated RAW 246.7 macrophage cell line. In acute inflammatory models in vivo (carragenean induced edema, carragenean induced pleurisy in rats and vascular permeability in mice), AAEE exhibited an extensive diverse mechanism for anti-inflammatory properties. This was indicated on the basis of dose dependent suppression of multi targeted inflammatory mediators., NO, TNF-α and IL-1ß, eicosanoids., PGE2 and leukotrienes., LTB4 along with significantly decreased leucocyte migration, exudation and decreased vascular permeability. These effects were more potent and prolonged than traditional NSAIDS, thereby indicating fewer side effects. AAEE was found to be safe for long term administration, as confirmed by the results of acute toxicity studies and MTT assay. The complex mode of action of the herbs was attributed possibly due to the high polyphenolic, flavanol and flavonoid content present in the extracts as observed by means of quantitative screening for phytochemicals. CONCLUSION: Our study provides scientific evidence to support the traditional anti-inflammatory uses of Atropa acuminata and is probably due to inhibitory effects on multiple inflammatory mediators which indicates a promising potential for the development of a strong anti-inflammatory agent from this plant.