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The floodplain wetland habitat in the lower Gangetic plains of West Bengal played a significant role in protecting from environmental degradation like pollution, lowering groundwater table, natural hazards, and others as well as supports for human wellbeing. Thus, it is needed to investigate the health status of wetlands and suggest restoration strategies to protect the livelihood patterns dependent on wetlands. This paper presents the health of the wetland ecosystem by comprising the wetland ecosystem health index (WHI) in 2011 and 2018 at the block level of Malda district, as a part of the lower Gangetic flood plain using the pressure-state-response model (PSR model) and AHP method. A total number of six Landsat satellite images and statistical census data were used to determine the wetland health. Wetlands are classified as very healthy (2.81-3.33), healthy (2.41-2.80), sub-healthy (2.01-2.40), unhealthy (1.61-2.00), and sick (0-1.60) category on the basis of the wetland ecosystem health index score. The results of this study showed that the wetlands located surrounding English Bazar, Manikchak, Ratua-II, and Kaliachak-II blocks have a sub-healthy to very healthy condition in 2011 but changed to unhealthy to sick category in 2018 due to the increase of rapid urbanization, population density, and development activities. These areas have belonged to the sub-healthy to sick category in the year 2011 as well as 2018 due to high wetland pressure. Our observation reveals that the ecosystem service value provided by wetlands decreased by 62.51% and 20.46 in the observed period. Management of WEH should emphasize on large (>100 ha) and medium (51-100 ha) sizes of wetlands in the Diara region of West Bengal. Developing local-level institutions and setting restoration goals are useful strategies to manage wetland resources, and protecting biodiversity should be guided by the Government organization and NGOs., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aberrant activation of Wnt/ β -catenin axis occurs in several gastrointestinal malignancies due to inactivating mutations of adenomatous polyposis coli (in colorectal cancer) or activating mutations of β -catenin itself [in hepatocellular carcinoma (HCC)]. These lead to β -catenin stabilization, increase in β -catenin/T-cell factor (TCF)-mediated transcriptional activation, and target gene expression, many of which are involved in tumor progression. While studying pharmaceutical agents that can target β -catenin in cancer cells, we observed that the plant compound berberine (BBR), a potent activator of AMP-activated protein kinase (AMPK), can reduce β -catenin expression and downstream signaling in HCC cells in a dose-dependent manner. More in-depth analyses to understand the mechanism revealed that BBR-induced reduction of β -catenin occurs independently of AMPK activation and does not involve transcriptional or post-translational mechanisms. Pretreatment with protein synthesis inhibitor cycloheximide antagonized BBR-induced β -catenin reduction, suggesting that BBR affects β -catenin translation. BBR treatment also antagonized mammalian target of rapamycin (mTOR) activity and was associated with increased recruitment of eukaryotic translation initiation factor 4E-binding protein (4E-BP) 1 in the translational complex, which was revealed by 7-methyl-cap-binding assays, suggesting inhibition of cap-dependent translation. Interestingly, knocking down 4E-BP1 and 4E-BP2 significantly attenuated BBR-induced reduction of β -catenin levels and expression of its downstream target genes. Moreover, cells with 4E-BP knockdown were resistant to BBR-induced cell death and were resensitized to BBR after pharmacological inhibition of β -catenin. Our findings indicate that BBR antagonizes β -catenin pathway by inhibiting β -catenin translation and mTOR activity and thereby reduces HCC cell survival. These also suggest that BBR could be used for targeting HCCs that express mutated/activated β -catenin variants that are currently undruggable. SIGNIFICANCE STATEMENT: β -catenin signaling is aberrantly activated in different gastrointestinal cancers, including hepatocellular carcinoma, which is currently undruggable. In this study we describe a novel mechanism of targeting β -catenin translation via utilizing a plant compound, berberine. Our findings provide a new avenue of targeting β-catenin axis in cancer, which can be utilized toward the designing of effective therapeutic strategies to combat β -catenin-dependent cancers., (U.S. Government work not protected by U.S. copyright.)

Introduction: Simulators are used for training competencies including blood pressure (BP) measurement. Whether such training translates to competency in real life is unclear., Methods: We randomized 145 first-year undergraduate medical students to train on a BP simulator or arms of colleagues. After training, all students were assessed for accuracy (within 4 mm Hg above or below assessor's simultaneous recording) and methodology of BP recordings by an objectively structured clinical examination on real patients., Results: Overall, 67 (46.2%) and 92 (63.4%) students accurately measured systolic and diastolic BP, respectively. Forty-three (58.1%) of 74 students in the conventional training recorded systolic BP accurately compared with 24 (33.8%) of 71 students in simulator training (P = 0.005). Diastolic BP was accurately recorded by 56 (75.7%) of 74 students in conventional group as against 36 (50.7%) of 71 students trained on simulator (P = 0.002). Median (interquartile range) objectively structured clinical examination score in conventional group was 8 (7-9) compared with 6 (5-7) in simulator group (P < 0.001)., Conclusions: Simulator-based training did not translate to clinical competence in terms of accuracy and methodology of BP recordings in real-life settings. Notwithstanding its advantages, simulator-based BP training needs integration with human element to make it meaningful and relevant to clinical practice.

Mixed lineage kinase 3 (MLK3), a MAP3K member has been envisioned as a viable drug target in cancer, yet its detailed function and signaling is not fully elucidated. We identified that MLK3 tightly associates with an oncogene, PAK1. Mammalian PAK1 being a Ste20 (MAP4K) member, we tested whether it is an upstream regulator of MLK3. In contrast to our hypothesis, MLK3 activated PAK1 kinase activity directly, as well as in the cells. Although, MLK3 can phosphorylate PAK1 on Ser133 and Ser204 sites, PAK1S133A mutant is constitutively active, whereas, PAK1S204A is not activated by MLK3. Stable overexpression of PAK1S204A in breast cancer cells, impedes migration, invasion, and NFĸB activity. In vivo breast cancer cell tumorigenesis is significantly reduced in tumors expressing PAK1S204A mutant. These results suggest that mammalian PAK1 does not act as a MAP4K and MLK3-induced direct activation of PAK1 plays a key role in breast cancer tumorigenesis.

Immunohistochemical markers have been proposed for thyroid cancer diagnosis and prognostic studies. Immunohistochemical analysis of CK-19, NF-kappaB, beta-catenin, E-cadherin and EGFR were done to evaluate their diagnostic and prognostic efficiencies in eighty eight cancer specimen (PTC-52, FTC-16, benign nodule-12 and MNG-8). CK-19 was positive in 91% (62/68) DTC, 98% (51/52) PTC, 69% (11/16) FTC and 15% (3/20) benign thyroid nodules. NF-kappaB was expressed 93% (63/68) DTC, in 96% (50/52) PTC, 81% (11/16) FTC and 15% (3/20) benign thyroid nodules. Both CK-19 and NF-kappaB were significantly differentiated DTC, PTC and FTC from benign thyroid nodule (p < 0.0001) with diagnostic accuracy of 89.74%, 94.4% and 77.4% for CK-19 and 91.0%, 90.5% and 83.5% respectively for NF-kappaB. Though CK-19 and NF-kappaB were equally sensitive but CK-19 was most specific in the diagnosis of DTC and PTC. The diagnostic accuracy of beta-catenin was 96% and 94% and accuracy of E-cadherin was 90.1% and 93.9% for the diagnosis of metastatic PTC and FTC respectively. EGFR showed 90% (18/20) of metastatic PTC (p < 0.0001) and sensitivity, specificity and accuracy were 90%, 71.8% and 78.85% respectively. CK-19 and NF-kappaB were accurately diagnosed in DTC, PTC and FTC whereas, NF-kappaB, E-cadherin, beta-catenin and EGFR were strongly expressed in invasive papillary thyroid cancers and FTC, thus can be important diagnostic and prognostic marker for FTC and metastatic PTC. This may be concluded that immunohistochemical expression of panel of markers CK-19, NF-kappaB, E-cadherin, beta-catenin and EGFR can be useful in diagnosis and prognosis of DTC.

In the present study, methanol extract of Ocimum gratissimum Linn (ME-Og) was tested against nicotine-induced murine peritoneal macrophage in vitro. Phytochemical analysis of ME-Og shown high amount of flavonoid and phenolic compound present in it. The cytotoxic effect of ME-Og was studied in murine peritoneal macrophages at different concentrations (0.1 to 100 microg/ml) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) method. To establish the protective role of ME-Og against nicotine toxicity, peritoneal macrophages from mice were treated with nicotine (10 mM), nicotine+ME-Og (1 to 25 microg/ml) for 12h in culture media. The significantly (P< 0.05) increased super oxide anion generation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, lipid peroxidation, protein carbonyls, oxidized glutathione levels were observed in nicotine-treated group as compared to control group; those were significantly (p < 0.05) reduced in ME-Og supplemented groups in concentration dependent manner. More over, significantly (p < 0.05) reduced antioxidant status due to nicotine exposure was effectively ameliorated by ME-Og supplementation in murine peritoneal macrophages. Among the different concentration of ME-Og, maximum protective effect was observed by 25 microg/ml, which does not produce significant cell cytotoxicity in murine peritoneal macrophages. These findings suggest the potential use and beneficial role of O. gratissimum as a modulator of nicotine-induced free radical generation, lipid-protein damage and antioxidant status in important immune cell, peritoneal macrophages.