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Approximately 15% of globally diagnosed breast cancers are designated as triple negative breast cancer (TNBC). In this study, we investigated the effect of the natural compound, Bis(2- ethyl hexyl) 1H-pyrrole-3,4-dicarboxylate (TCCP), purified from Tinospora cordifolia on MDA-MB-231, a TNBC cell line. The pro-apoptotic nature of TCCP on MDA-MB-231 was determined by assessing various apoptotic markers. ROS generation, intracellular calcium, mitochondrial membrane potential (ΔΨm), MPTP, cardiolipin peroxidation and caspase activity were determined fluorometrically. BAX, BCL-2, cytochrome c, caspases, and p53 protein expressions were determined by immunoblotting. Further, the effect of TCCP on DNA and cell death was determined by DNA fragmentation assay, annexin-V staining, and cell cycle analysis. TCCP treatment caused endogenous ROS generation, increase in intracellular calcium and phosphorylation of p53 in a concentration-dependent manner, which was reverted upon pre-treatment with pifithrin-μ. This led to the downstream altered expression of Bcl-2 and Bax proteins, mitochondrial membrane depolarization, MPTP, and cardiolipin peroxidation. TCCP induced cytochrome c release into the cytosol, caspase activation, ultimately resulting in DNA fragmentation. Further, induction of apoptosis and morphological alterations were evident from the phosphatidylserine externalization and increase in sub G1 population. The in vivo Ehrlich ascites tumor (EAT) mouse study revealed the effectiveness of TCCP in reducing the tumor burden and resulted in a ~2 fold increase in mice survival with minimal hepato-renal toxicity. Overall, TCCP was shown to be efficient in inducing ROS and mitochondrial-mediated apoptosis by restoring p53 activity in MDA-MB-231 cells and also induced EAT cell death in vivo thereby inhibiting tumor proliferation.

Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities. Considering aspirin insensitivity in DM patients, new therapies targeting the underlying mechanism is urgently warranted. Berberine, a benzylisoquinoline alkaloids, from Chinese folk medicine has been demonstrated with several anti-diabetic effects. Therefore, we evaluated whether berberine inhibits high glucose potentiated platelet aggregation, apoptosis and further evaluated the mechanism of its action in platelets. Berberine was found to inhibit platelet aggregation, superoxide production via modulating AR, NOX, and glutathione reductase activities in high glucose (HG) treated platelets. Correlated with this, berberine inhibited, calcium release, ERK activation, α- and dense granule release and platelet adhesive properties. In addition, berberine inhibited p38-p53 mediated BAX activation, mitochondrial dysfunction and platelet apoptosis induced by HG. The platelet protective effect of berberine by inhibiting AR and NOX in high glucose-treated platelets suggest that berberine could be developed as a potential therapeutic molecule in the treating pathologies associated with DM.

Aquatic bryophytes can accumulate extremely high levels of chemical elements because of their unique morphology and physiology which is markedly different from vascular plants. Four aquatic mosses—Fontinalis squamosa, Brachythecium rivulare, Platyhypnidium riparioides, Thamnobryum alopecurum—and a freshwater red alga Lemanea fluviatilis along with water samples from the streams of Gois mine region in Central Portugal were analyzed for 46 elements. Despite being below detection levels in the water samples, the elements Zr, V, Cr, Mo, Ru, Os, Rh, Ir, Pt, Ag, Ge and Bi were obtained in the plant samples. The moss T. alopecurum had the highest mean concentrations of 19 elements followed by B. rivulare (15 elements). Maximum accumulation of Rb, Ta and Au, however, was seen in the alga L. fluviatilis. Bioconcentration factors > 106 were obtained for a few metals. The investigation confirms that aquatic bryophytes can be suitable for water quality biomonitoring and biogeochemical prospecting in fresh water bodies owing to their high accumulative capacity of multi-elements from their aquatic ambient.

Arbuscular mycorrhizal fungi (AMF) aids in plant establishment at heavy metal(loid) (HM) contaminated soils, strengthening plant defense system along with promoting growth. A pot experiment was carried out to evaluate the effect of AMF on eggplants grown under HM stress. Further, the potential health risks of HM exposure to the humans via dietary intake of eggplant were also estimated. Results showed that AMF application improved growth, biomass and antioxidative defense response of plants against HM stress. Significant difference (p ≤ 0.001) in parameters under study was found on increasing metal dose and on application of AMF. Among metal(loid)s maximum uptake was recorded for Pb (29.64mgkg-1 in roots; 23.08mgkg-1 in shoot) followed by As (3.84mgkg-1 in roots; 8.20mgkg-1 in shoot) and, Cd (0.96mgkg-1 in roots; 2.12mgkg-1 in shoot). Based on the accumulation of HM in edible part, Hazard Quotient (HQ) was calculated. HQ was found to be > 1 for Pb, which highlights the risks associated with consumption of Eggplants grown on Pb contaminated soil. However this potential, which was further enhanced by application of AMF, can be harnessed for on-site remediation of Pb contaminated soils. The content of Cd and As in the edible part was found to be within safe limits (HQ < 1) when compared to chronic reference dose stated by USEPA.

Platelets are anucleate cells, known for their pivotal roles in hemostasis, inflammation, immunity, and disease progression. Being anuclear, platelets are known to express several transcriptional factors which exert nongenomic functions, including the positive and negative regulation of platelet activation. NF-κB is one such transcriptional factor involved in the regulation of genes for survival, proliferation, inflammation and immunity. Although, the role NF-κB in platelet activation and aggregation is partially known, its function in management of platelet survival and apoptosis remain unexplored. Therefore, two unrelated inhibitors of NF-κB activation, BAY 11-7082 and MLN4924 were used to determine the role of NF-κB in platelets. Inhibition of NF-κB caused decreased SERCA activity and increased cytosolic Ca2+ level causing ER stress which was determined by the phosphorylation of eIF2-α. Further, there was increased BAX and decreased BCl-2 levels, incidence of mitochondrial membrane potential depolarization, release of cytochrome c into cytosol, caspase activation, PS externalization and cell death in BAY 11-7082 and MLN4924 treated platelets. The obtained results demonstrate the critical role played by NF-κB in Ca2+ homeostasis and survival of platelets. In addition, the study demonstrates the potential side effects associated with NF-κB inhibitors employed during inflammation and cancer therapy.

Turmeric and commercial curcumin contains curcumin, desmethoxycurcumin and bisdesmethoxycurcumin as major components and they exhibit potential biological applications. Controlled crystallization of curcuminioids could lead to formation of new polymorphs/with different morphological features. In this report the structure and morphological changes taking place during the crystallization of curcuminoid mixture as well as individual curcuminoid polymorphs at different temperatures have been reported. The samples have been characterized using powder X-ray diffraction, infrared spectroscopy, 1H and 13C NMR and scanning electron microscopy. Our results show that curcumin exhibit polymorphs of which curcumin form 1 (monoclinic crystal system) has rod like morphology while curcumin form 2 (orthorhombic crystal system) shows sheet like morphology. Desmethoxycurcumin and bisdesmethoxycurcumin does not exhibit polymorphism and possess spherical shape and irregular morphology respectively.

Curcumin, a major bioactive component of turmeric (Curcuma longa), is known for its multiple health benefits. Curcumin as such is a mixture of its analogs: bisdemethoxycurcumin (BDMC)-3%, and demethoxycurcumin (DMC)-17%. Although the effect of curcumin on platelets is documented, the effect of BDMC and DMC on platelets is less studied. Considering the indispensable role played by platelets in hemostasis, thrombosis, inflammation, and immunity, the present study evaluates the effect of curcumin, DMC and BDMC on platelet apoptosis. The components of curcumin were purified by silica-gel column chromatography. The purity and mass analysis of the purified curcuminoids was determined by RP-HPLC and LC-MS respectively. When analyzed for platelet apoptotic markers, only BDMC demonstrated increased incidence of platelet apoptotic markers including increase in intracellular Ca2+, decrease in ∆ψm, alteration in BCl-2 family proteins, the release of cytochrome c, caspase activation, and PS externalization via activation of ERK activation. ERK inhibitor PD98059 significantly alleviated BDMC induced decrease in ∆ψm, alteration in BCl-2, caspase-8 activation and PS externalization. Our results demonstrate that curcumin, DMC and BDMC differentially act on platelet in inducing apoptosis and the study highlights that the toxicity associated with curcumin therapy might be attributed to BDMC in the mammalian system.

A study was undertaken to determine Uranium concentrations in water and aquatic plants in the uraniferous region of Beiras, Central Portugal. Samples were collected from running water (n = 200) at places where aquatic species were observed. Plant samples were collected from 28 species of submerged, free-floating and rooted emergent plants including 2 bryophytes and 1 pteridophyte. Uranium concentrations in surface waters ranged from 0.23 to 1217 μg L − 1 . The aquatic plant species studied, including several previously untested species, exhibited the ability to accumulate U in concentrations many times that of the ambient water. In general submerged plants exhibited higher U content followed by rooted emergent and free floating species. The highest U concentrations were observed in the bryophyte Fontinalis antipyretica (up to 4979 mg kg − 1 ) followed by Callitriche stagnalis (1963 mg kg − 1 ), Callitriche hamulata (379 mg kg − 1 ), Ranunculus peltatus subsp. saniculifolius (243 mg kg − 1 ), Callitriche lusitanica (218 mg kg − 1 ), and Ranunculus trichophyllus (65.8 mg kg − 1 ). In two out of three rooted emergent species U seemed to be preferentially partitioned in rhizome/roots with highest rhizome U content recorded in Typha latifolia (380 mg kg − 1 ). Among the free-floating species, the highest U content (42.5 mg kg − 1 ) was seen in Lemna minor . The bryophyte F. antipyretica and Callitrichaceae members seem to be promising candidates for the development of phytofiltration methodologies based on U accumulation, abundance and biomass production.

A pot study was conducted to assess the phytoremediation potential of Spinach plants along with their physiological and biochemical response when grown in soil contaminated with heavy metal(loid)s (HMs). Plants were grown under different doses of Pb, Cd and As; and their metal(loid) accumulation efficiency was studied upon harvest; expressed in terms of bioabsorption coefficient (BAC), bioconcentration factor (BCF) and translocation factor (TF). Results showed significant (p ≤ 0.05) difference in physiological and biochemical mechanisms of plants as detected through decrease in concentration of cellular constituents (pigments, carbohydrates, total nitrogen content); and increase in antioxidants (both enzymatic and non-enzymatic). Despite of accumulating high amount of HMs in tissues, no visible signs of toxicity were seen; and hence the efficient survival and defense mechanism shown by spinach plants conclude that they are a viable option to be used for phytoremediation of sites contaminated with Cd and Pb. Since the content of Cd and Pb in edible part was higher than safe limits prescribed by USEPA, the present investigation also highlights the ecological hazards that may result upon cultivation of spinach in contaminated soil for agricultural purpose; or its accidental exposure to food chain when grown for phytoremediation.

Lead and cadmium levels were monitored in soil at fifteen urban (riverbank, roadside, industrial and residential) sites in the north central part of India. Calotropis procera, a hardy xerophytic plant was identified and selected for remedial potential as it was seen growing well at all sites. Root and leaf samples were collected simultaneously with soil samples to assess the characteristics of accumulation and tolerance of Pb and Cd in C. procera. Chlorophyll and phenological studies were undertaken to investigate the health of plants. The overall trend of Pb and Cd content in soil and plant samples was in the order Industrial>Roadside>Riverbank>Residential. The highest uptake of both the metals was observed in plants from industrial sites. Sites with more anthropogenic disturbance like vehicular and machinery exhausts exhibited reduced chlorophyll levels, stunted growth as well as a delayed, shortened reproductive phase. The ratios of Pb in leaves to Pb in soil were in the range of 0.60-1.37; while similar ratios of Cd were in the range of 1.25-1.83. Highly significant correlation coefficients were determined between concentrations of Pb and Cd in the samples with R(2) values 0.839 for soil, 0.802 for leaf and 0.819 for root samples. The strong correlation between the degree of contamination and concentrations of Pb and Cd in plant samples identifies C. procera as an effective heavy metal remediator of contaminated lands coupled with environmental stress.