Anticancer activity of Bacopa monnieri through apoptosis induction and mitophagy-dependent NLRP3 inflammasome inhibition in oral squamous cell carcinoma.

BACKGROUND: Bacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood. AIM: The aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics. RESULTS: We performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice. CONCLUSION: In conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.

Regional and temporal variability of Indian summer monsoon rainfall in relation to El Niño southern oscillation.

The Indian summer monsoon rainfall (ISMR) exhibits significant variability, affecting the food and water security of the densely populated Indian subcontinent. The two dominant spatial modes of ISMR variability are associated with the El Niño Southern Oscillation (ENSO) and the strength of the semi-permanent monsoon trough along with related variability in monsoon depressions, respectively. Although the robust teleconnection between ENSO and ISMR has been well established for several decades, the major drivers leading to the time-varying relationship between ENSO and ISMR patterns across different regions of the country are not well understood. Our analysis shows a consistent increase from a moderate to substantially strong teleconnection strength between ENSO and ISMR from 1901 to 1940. This strengthened relationship remained stable and strong between 1941 and 1980. However, in the recent period from 1981 to 2018 the teleconnection decreased consistently again to a moderate strength. We find that the ENSO-ISMR relationship exhibits distinct regional variability with time-varying relationship over the north, central, and south India. Specifically, the teleconnection displays an increasing relationship for north India, a decreasing relationship for central India and a consistent relationship for south India. Warm SST anomalies over the eastern Pacific Ocean correspond to an overall decrease in the ISMR, while warm SST anomalies over the Indian Ocean corresponds to a decrease in rainfall over the north and increase over the south of India. The central Indian region experienced the most substantial variation in the ENSO-ISMR relationship. This variation corresponds to the variability of the monsoon trough and depressions, strongly influenced by the Pacific Decadal Oscillation and North Atlantic Oscillation, which regulate the relative dominance of the two spatial modes of ISMR. By applying the PCA-Biplot technique, our study highlights the significant impacts of various climate drivers on the two dominant spatial modes of ISMR which account for the evolving nature of the ENSO-ISMR relationship.

Theoretical study of highly efficient all-inorganic Sb2S3-on-Si monolithically integrated (2-T) and mechanically stacked (4-T) tandem solar cells using SCAPS-1D.

The power conversion efficiency of all-inorganic Sb2S3-on-Si two-terminal (2-T) monolithically integrated and four-terminal (4-T) mechanically stacked tandem solar cells are investigated. A one-dimensional solar cell capacitance simulator (SCAPS-1D) has been used to simulate the stand-alone antimony trisulfide (Sb2S3) top sub-cell, silicon (Si) bottom sub-cell, 2-T monolithic, and 4-T mechanically stacked tandem solar cells. The stand-alone sub-cells are optimized by extensive studies, including interface defects density, bulk defects density, absorber layer thickness, and series resistance. The power conversion efficiency (PCE) of simulated stand-alone sub-cells is compared and verified with the existing literature. A current matching condition is established to characterize the 2-T monolithic Sb2S3-on-Si tandem cell. A filtered spectrum has been utilized for bottom sub-cell measurement in the tandem solar cells. The best-simulated PCE of Sb2S3-on-Si 2-T monolithic and 4-T tandem cells is 30.22% and 29.30%, respectively. The simulation results presented in this paper open an opportunity for the scientific community to consider Sb2S3 as a potential top sub-cell material in Sb2S3-on-Si tandem solar cells with high PCE.

Performance analysis of n-TiO2/p-Cu2O, n-TiO2/p-WS2/p-Cu2O, and n-TiO2/p-WS2 heterojunction solar cells through numerical modelling.

A new hetero-structure of n-TiO2/p-WS2/p-Cu2O is proposed as a potential candidate for solar energy generation using tungsten disulfide (WS2) as an absorber layer. The proposed device performance is simulated by employing a one-dimensional solar cell capacitance simulator (SCAPS-1D). The numerical simulation studies compared the performances of n-TiO2/p-Cu2O, n-TiO2/p-WS2/p-Cu2O, and n-TiO2/p-WS2 hetero-structures based on various physical parameters like interface defects density, bulk defects density, absorber layer thickness, series resistance, shunt resistance, and operating temperature. In our simulation investigations, we found that interface defects pose a formidable impact on heterojunction devices. Interface defects closer to the front surface severely deteriorate the performances than the back surface. The bandgap of the absorber layer influences the performances of the solar cells. A closer comparison between n-TiO2/p-Cu2O and n-TiO2/p-WS2 heterojunction solar cells (HJSCs) revealed that the latter (n-TiO2/p-WS2) has nearly 182% better performance than the former (n-TiO2/p-Cu2O) devices. Additionally, the performance of the n-TiO2/p-WS2 solar cell is further boosted by ~ 139% in the presence of a hole transport layer of p-Cu2O. The best-simulated efficiency of the proposed new hetero-structure (n-TiO2/p-WS2/p-Cu2O) solar cell is 28.86%. Moreover, these optimized physical parameters may shed light on "easy to apply" new path for fabrication of a non-toxic, environment-friendly, and highly efficient novel thin-film heterojunction (n-TiO2/p-WS2/p-Cu2O) solar cell.

Microbial Journey: Mount Everest to Mars.

A rigorous exploration of microbial diversity has revealed its presence on Earth, deep oceans, and vast space. The presence of microbial life in diverse environmental conditions, ranging from moderate to extreme temperature, pH, salinity, oxygen, radiations, and altitudes, has provided the necessary impetus to search for them by extending the limits of their habitats. Microbiology started as a distinct science in the mid-nineteenth century and has provided inputs for the betterment of mankind during the last 150 years. As beneficial microbes are assets and pathogens are detrimental, studying both have its own merits. Scientists are nowadays working on illustrating the microbial dynamics in Earth's subsurface, deep sea, and polar regions. In addition to studying the role of microbes in the environment, the microbe-host interactions in humans, animals and plants are also unearthing newer insights that can help us to improve the health of the host by modulating the microbiota. Microbes have the potential to remediate persistent organic pollutants. Antimicrobial resistance which is a serious concern can also be tackled only after monitoring the spread of resistant microbes using disciplines of genomics and metagenomics The cognizance of microbiology has reached the top of the world. Space Missions are now looking for signs of life on the planets (specifically Mars), the Moon and beyond them. Among the most potent pieces of evidence to support the existence of life is to look for microbial, plant, and animal fossils. There is also an urgent need to deliberate and communicate these findings to layman and policymakers that would help them to take an adequate decision for better health and the environment around us. Here, we present a glimpse of recent advancements by scientists from around the world, exploring and exploiting microbial diversity.

Optimization and Validation of a Multiresidue Method for Screening of 126 Pesticide Residues in Herbal Raw Materials and Extracts Used as Ingredients in Ayurvedic Medicines and Dietary Supplements.

BACKGROUND: Testing for pesticide levels in herbal products is an important aspect in determining product safety. Plants and their extracts are widely used as ingredients in botanical dietary supplements and traditional medicines. The extracts of plants, especially those prepared out of organic solvents, are rich in secondary metabolites and pigments, and adequate clean-up is required since the extracts completely dissolve in organic solvents. OBJECTIVE: The study aims at reporting a multiresidue analytical method for 126 different pesticides in raw material biomass as well as extracts of plants, which are widely used as ingredients in ayurvedic medicines as well as dietary supplements using LC-MS/MS and GC-MS/MS with a rugged sample preparation technique for accurate results. METHOD: QuEChERS (quick, easy, cheap,effective, rugged, and safe) procedure, gel permeation chromatography (GPC), GPC coupled with solid phase extraction (SPE), and liquid-liquid extraction (LLE) coupled with SPE sample preparation methods were compared against each other for suitability to test pesticides in selected herbal raw materials and their alcoholic and aqueous extracts. The standard addition method was used for quantifying the level of pesticides below 10 µg/kg. RESULTS: Single laboratory validation for sample preparation involving GPC and SPE resulted linearity in the range of 2.5-500 ng/mL, average intraday and interday precision of 6.6% RSD, and average recovery (spiked at 10 µg/kg) of 92% for all analytes tested. The method was repeatable with different analysts and days. CONCLUSIONS: The sample preparation technique combining GPC and SPE as well as LLE and SPE was the most suitable for the selected herbal alcoholic extracts, whereas any of the regular techniques involving LLE, SPE, and QuEChERS were suitable for raw material biomass as well as aqueous extracts. HIGHLIGHTS: The method was found to be capable of determining selected pesticides in the selected matrixes at 10 µg/kg concentration. Provision of recycling solvents used in the GPC+SPE method was adopted to make the method environmentally friendly.

Role of warm ocean conditions and the MJO in the genesis and intensification of extremely severe cyclone Fani.

Cyclone Fani, in April 2019, was the strongest pre-monsoon cyclone to form in the Bay of Bengal after 1994. It underwent rapid intensification and intensified quickly to an extremely severe cyclone. It maintained a wind speed of ≥ 51 m s-1 (≥ 100 knots) for a record time period of 36 h. The total lifespan of the cyclone was double than the climatological lifespan. Also, the duration of the cyclone in its extremely severe phase and the accumulated cyclone energy were significantly larger than the climatological records for the pre-monsoon season. In the current study, we investigate the ocean-atmospheric conditions that led to its genesis, rapid intensification and long lifespan. Our analysis shows that the Madden Julian Oscillation and anomalous high sea surface temperatures provided conducive dynamic and thermodynamic conditions for the genesis of cyclone Fani, despite forming very close to the equator where cyclogenesis is generally unlikely. Further, favourable ocean subsurface conditions and the presence of a warm core eddy in the region led to its rapid intensification to an extremely severe cyclone. A large area of warm ocean surface and subsurface temperatures aided the cyclone to maintain very high wind speed for a record time period. The vital role of the ocean surface and the subsurface in the genesis and the intensification highlights the need to efficiently incorporate ocean initial conditions (surface and sub-surface) and ocean-atmosphere coupling in the operational cyclone forecasting framework.

Breeding System and Response of the Pollinator to Floral Larceny and Florivory Define the Reproductive Success in Aerides odorata.

Consumption of pollination reward by felonious means in a plant species can influence the foraging behavior of its pollinator and eventually the reproductive success. So far, studies on this aspect are largely confined to interaction involving plant-pollinators and nectar robbers or thieves. However, a foraging guild in such interactions may also include floral herbivores or florivores. There is a paucity of information on the extent to which nectar larcenists may influence the foraging behavior of the pollinator and reproductive fitness of plants in the presence of a florivore. We investigated various forms of larceny in the natural populations of Aerides odorata, a pollinator-dependent and nectar-rewarding orchid. These populations differed in types of foraging guild, the extent of larceny (thieving/robbing), which can occur with or without florivory, and natural fruit-set pattern. The nectariferous spur of the flower serves as an organ of interest among the foraging insects. While florivory marked by excision of nectary dissuades the pollinator, nectar thieving and robbing significantly enhance visits of the pollinator and fruit-set. Experimental pollinations showed that the species is a preferential outbreeder and experiences inbreeding depression from selfing. Reproductive fitness of the orchid species varies significantly with the extent of floral larceny. Although nectar thieving or robbing is beneficial in this self-compatible species, the negative effects of florivory were stronger. Our findings suggest that net reproductive fitness in the affected plant species is determined by the overarching effect of its breeding system on the overall interacting framework of the foraging guild.

A Perspective on Additional Approaches Beyond Organic Marker Compounds While Developing Analytical Monographs for Botanicals.

Most of the Pharmacopoeia and other monographs that provide the quality specifications for botanicals typically contain identification and physicochemical tests, assays, and limits for contaminants. The assay methods generally involve quantitative determination of known organic compounds, commonly known as markers. The authors explore and propose that there is a need for additional approaches beyond markers, especially for botanicals derived from traditional knowledge and use. Preliminary data on few selected botanicals are additionally provided to communicate the thought process.

Relative contribution of reproductive attributes to the density-dependent effects on fruit-set.

Reproductive success of a plant species can be affected by the distribution pattern of its conspecifics in a small population. Besides the low mate availability, the dynamics of breeding system and pollination mechanism may also contribute to low fruit-set in such populations. We examined the relative contribution of these reproductive attributes on fruit-set across the contrasting distribution pattern (denser vs. sparser plots) in two isolated natural populations of a near-threatened tree species, Anogeissus sericea var. nummularia. Although flowers in the species are of generalist type, the narrow stigmatic surface appears to impose a requirement for a specialist pollinator. Pollination in the tree species is mediated only by the flies. The trees exhibit partial selfing and suffer from strong inbreeding depression at the early life-history stages of the selfed progeny. We recorded significant difference between the denser and sparser plots in terms of inflorescence visits per tree, and the number of trees covered in a bout by the pollinators. Moreover, tree density showed a strong positive correlation with fruit-set. Besides the requirement of having proximity among the conspecifics to facilitate pollinator movement, pollen quality also seemed to be a crucial attribute in the reproductive success of the tree species. It is inferred that the mating pattern and fecundity of plants in small and isolated populations are significantly influenced by the extent of sexual incompatibility and magnitude of their dependence on pollinators.

Gymnemic Acid Stimulates In Vitro Splenic Lymphocyte Proliferation.

Gymnemic acid is a mixture of triterpenoid saponins of oleanane class, isolated from Gymnema sylvestre Wild R.Br (family: Asclepidaceae), an herbal plant used in traditional medicine to treat diabetes. Effect of gymnemic acid (0.1-20 µg/mL) on in vitro mitogen (concanavalin A and lipopolysaccharide)-induced splenic lymphocyte proliferation was studied using rat as model. Significant (p < 0.05) stimulation of lymphoproliferation was observed in cultures treated with 10 and 20 µg/mL concentration of gymnemic acid in the absence or presence of mitogens. The present study suggests that gymnemic acid has immunomodulatory property, stimulating lymphoid components of immune system, and the traditional knowledge of anti-diabetic property of G. sylvestre is scientifically supplemented with its immunomodulatory properties.

Immunomodulatory Effect of Gymnema sylvestre (R.Br.) Leaf Extract: An In Vitro Study in Rat Model.

Gymnema sylvestre Wild R.Br (family: Asclepidaceae) is a valuable medicinal plant used in folk medicine to treat diabetes, obesity, asthma etc. in India for antiquity. Diabetes mellitus is a syndrome characterized immunologically by lymphocyte apoptosis and reduced cell-mediated and humoral immunity. Modulation of immune responses to alleviate diseases has been of interest, and traditional herbal medicines may play an important role in this regard. In this study, we aim to evaluate the immunomodulatory potential of methanolic extract of G. sylvestre leaf using rat model. HPLC analysis of leaf extract was carried out for gymnemic acid. The method involves the initial hydrolysis of gymnemic acids, the active ingredients, to a common aglycone followed by the quantitative estimation of gymnemagenin, using gymnemagenin as reference standard. Gymnemic acid content was 2.40% (w/w) in G. sylvestre leaf extract. In vitro immunomodulatory activity of the methanolic extract of G. sylvestre leaf (1-200µg/ml) was evaluated by gauging its effects on nitroblue tetrazolium reduction and nitrite release in rat peritoneal macrophages and on mitogen (ConA, PHA and LPS) induced splenic lymphocyte proliferation. G. sylvestre leaf extract showed significant (<0.05) enhancement in NO and ROS generation in macrophages and in proliferation of lymphocytes in dose dependent manner. EC50 value was 3.10, 3.75 and 2.68 µg/ml for NBT reduction, nitrite release and lymphoproliferation, respectively. Potential effect was observed at 100 µg/ml in NO and ROS generation in macrophages and 20 µg/ml in lymphocyte proliferation. G. sylvestre leaf extract stimulates macrophage reactivity, increasing the level of activity even higher when combined with PMA or LPS. These findings suggest the presence of active compounds, gymnemic acid, in methanolic extract of G. sylvestre leaf that stimulates both myeloid and lymphoid components of immune system, and therefore can restore the innate immune function. Through this study, the traditional knowledge of anti-diabetic property of G. sylvestre is scientifically supplemented with its immunomodulatory properties.

Aldose reductase and protein tyrosine phosphatase 1B inhibitory active compounds from Syzygium cumini seeds.

CONTEXT: Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as jamun, is an Indian plant, traditionally well known for its medicinal properties including antidiabetic activity. OBJECTIVE: To isolate the antidiabetic compounds from Syzygium cumini seeds and evaluate their activity using aldose reductase (AR) and protein-tyrosine phosphatase 1B (PTP1B) inhibition assays. MATERIALS AND METHODS: The dried seeds were extracted with methanol and partitioned with ethyl acetate, butanol, and water. The extracts were screened for antidiabetic activity at a concentration of 100 µg/mL using in vitro AR and PTP 1B inhibition assays. RESULTS AND DISCUSSION: The highly enriched fractions obtained from broad ethyl acetate fraction yielded maslinic acid (1), 5-(hydroxymethyl) furfural (2), gallic acid (3), valoneic acid dilactone (4), rubuphenol (5), and ellagic acid (6). Structures were elucidated by (1)H-NMR and (13)C-NMR. The initial ethyl acetate fraction showed AR inhibitory activity with the IC50 value of 2.50 µg/mL and PTP1B enzyme inhibition with the IC50 value of 26.36 µg/mL. Compounds 3, 4, 5, and 6 were found to inhibit AR with IC50 values of 0.77, 0.075, 0.165, and 0.12 µg/mL while the compounds 4, 5, and 6 inhibited PTP1B with IC50 values of 9.37, 28.14, and 25.96 µg/mL, respectively. CONCLUSION: The results of this study demonstrate that the isolated constituents show promising in vitro antidiabetic activity and, therefore, can be candidates for in vivo biological screening using relevant models to ascertain their antidiabetic activity.

Cycloolivil, a lignan from the roots of Stereospermum suaveolens.

BACKGROUND: Stereospermum suaveolens DC. (Syn. S. chelonoides) belonging to family Bignoniaceae is an important medicinal plant in India. Traditionally, it is mainly used as analgesic, liver stimulant, astringent, wound healing and antidyspeptic. Roots of this plant are one of the ingredients of Dashamularishta. The plant has been studied for many pharmacological actions, only few were concerned with isolation of active compounds. OBJECTIVE: The present work deals with the isolation and identification of phytochemical constituents present in the roots of Stereospermum suaveolens. MATERIAL AND METHODS: The compounds were isolated from the ethyl acetate-soluble fraction from the methanol extract of S. suaveolens by using open silica gel column chromatography and HPLC was carried out for all the fractions to target the major peaks in fractions. RESULTS AND CONCLUSION: The isolated compounds structures were elucidated by analysis of spectroscopic data (UV, IR, 1D-NMR, and MS) and characterized as Cycloolivil (1) reported for the first time from this plant species, Lapachol (2) and ß-sitosterol (3), respectively.

Nectar robbing positively influences the reproductive success of Tecomella undulata (Bignoniaceae).

The net consequence of nectar robbing on reproductive success of plants is usually negative and the positive effect is rarely produced. We evaluated the influence of nectar robbing on the behaviour of pollinators and the reproductive success of Tecomella undulata (Bignoniaceae) in a natural population. Experimental pollinations showed that the trees were strictly self-incompatible. The three types of floral colour morphs of the tree viz. red, orange and yellow, lacked compatibility barriers. The pollinators (Pycnonotus cafer and Pycnonotus leucotis) and the robber (Nectarinia asiatica) showed equal preference for all the morphs, as they visited each morph with nearly equal frequency and flower-handling time. The sunbirds caused up to 60% nectar robbing, mostly (99%) by piercing through the corolla tube. Although nectar is replenished at regular intervals, insufficient amount of nectar compelled the pollinators to visit additional trees in bloom. Data of manual nectar robbing from the entire tree showed that the pollinators covered lower number of flowers per tree (5 flowers/tree) and more trees per bout (7 trees/bout) than the unrobbed ones (19 flowers/tree and 2 trees bout). The robbed trees set a significantly greater amount of fruits than the unrobbed trees. However, the number of seeds in a fruit did not differ significantly. The study shows that plant-pollinator-robber interaction may benefit the self-incompatible plant species under conditions that increases the visits of pollinators among the compatible conspecifics in a population.

Study of pressure induced phase transformation in CTAB capped CdS nanoparticles.

Effect of high pressure on as prepared 20mM CTAB capped CdS nanoparticles (size ~4nm) has been analyzed in this paper. Raman scattering has been used to observe the phase transition pressure. X-ray diffraction pattern is used for structural characterization. Raman scattering predicts the phase transition occur from mixed cubical phase to rock salt phase above 6.6 GPa. One of the representative XRD pattern at 9.7 GPa confirms the existence of rock salt phase above 6.6 GPa.

In vitro effects of certain membrane-acting agents on superoxide and hydrogen peroxide production, protein synthesis and membrane ATPase activity in buffalo PMN cells.

Polymorphonuclear (PMN) cells play a key role in innate immunity, due to their ability to produce reactive oxidants such as superoxide (O(2-)) and hydrogen peroxide (H(2)O(2)), and to release antimicrobial proteins and peptides stored in their lysosomal granules. In the present study, the effects of the activation of buffalo PMN cells with various membrane-acting agents were evaluated in terms of O(2-) and H(2)O(2) production, the activities of membrane ATPases, and protein synthesis. Studies involving the incorporation of (35)S-methionine revealed significant protein-synthesising ability in resting PMN cells and in cells treated with lipopolysaccharide (LPS), as well as with opsonised zymosan (OZ). Protein synthesis, as judged by fluorography of the cytosolic fraction, showed more than 12 bands, whilst the cytoskeletal fraction showed 2-3 bands. PMN activation with concanavalin A (ConA), digitonin and sodium nitroprusside (SNP) resulted in increased O(2-) and H(2)O(2) production. However, in the presence of anti-inflammatory agents such as indomethacin and cortisol, the production of O(2-) and H(2)O(2) by these cells was found to decline. Studies pertaining to membrane ATPases revealed that verapamil hydrochloride (VpHCl) significantly increased total ATPase and Na(+)K(+)ATPase activity. ConA treatment yielded only a moderate level of activity. Similarly, digitonin up to 24microM also caused a significant increase in ATPase activity. Our observations indicate that these membrane-acting agents influenced oxygen-dependent and oxygen-independent microbicidal mechanisms in buffalo PMN cells.