Role of Citrus Concentrate in Extraction and Evaluation of Herbal Polymer

Background: The use of natural polymers as excipients in the pharmaceutical sector is expanding day by day. Low cost, safety issues, availability, and biodegradability are the main causes that make them differ from other sources. Natural sources have a wide range of varieties and characteristics. So, they can be used numerous times in pharmaceutical products as excipients to serve the desired purposes.  Aim:  To extract and evaluate the natural polymeric substances that can be used as excipients in pharmaceuticals from fenugreek seeds by using solvent extraction method. Methods: Trigonella foenum-graceum fenugreek mucilage is drive from the endosperm of the seeds it consists of galactose and mannose of it gives high viscosity in aqueous solution the fenugreek seeds used for thickening, stabilizing and emulsifying food agent. In this procedure we use grapefruit juice to treat with extract mucilage from fenugreek seeds which enhance its stability and bioavailability. Grapefruit juice increases the bioavailability of some orally administered drugs that are metabolized by CYP3A4 and normally undergo extensive presystemic extraction. Results: In addition, grapefruit juice it can decrease the oral absorption of a few drugs that rely on organic anion transporting polypeptide in the gastrointestinal tract for their uptake. The number of drugs shown to interact with grapefruit juice in vitro is far greater than the number of clinically relevant grapefruit juice drug interactions

Dynamics and drivers of land use and land cover changes in Bangladesh

Bangladesh has undergone dramatic land use and land cover changes (LULCC) in recent years, but no quantitative analysis of LULCC drivers at the national scale exists so far. Here, we quantified the drivers of major LULCC in combination with biophysical and socioeconomic observations at the sub-district level. We used Landsat satellite data to interpret LULCC from 2000 to 2010 and employed a Global SurfaceWater Dataset to account for the influences of water seasonality. The results suggest that major LULCC in Bangladesh occur between agricultural land and waterbodies and between forest and shrubland. Exclusion of seasonal waterbodies can improve the accuracy of our LULCC results and driver analysis. Although the gross gain and loss of agricultural land are large on the local scale, the net change (gross gain minus gross loss) at a country scale is almost negligible. Climate dynamics and extreme events and changes in urban and rural households were driving the changes from forest to shrubland in the southeast region. The conversion from agricultural land to standing waterbodies in the southwest region was mainly driven by urban household dynamics, population growth, distance to cities and major roads, and precipitation dynamics. This study, which is the first effort accounting for water seasonality and quantifying biophysical and socioeconomic drivers of LULCC at the national scale, provides a perspective on overall LULCC and underlying drivers over a decadal time scale and national spatial scale and can serve as a scientific basis for developing land policies in Bangladesh

RNA-Based Therapies: A Cog in the Wheel of Lung Cancer Defense

Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies

Impact of drying on techno-functional and nutritional properties of food proteins and carbohydrates - A comprehensive review

This is the final version. Available on open access from Taylor & Francis via the DOI in this recordData availability statement: There is no data available for this article.Foods comprise of many macromolecules that have varying techno-functional and nutritional properties. The isolated proteins and carbohydrates from them are increasingly being used as potential ingredients in the food industries. Numerous processes like drying for food processing and preservation cause variations in functional and nutritional attributes of proteins and carbohydrates in different degrees in the food products that can ultimately affect their possible applications. This article explores different drying technologies being used in the food industries, including freeze-drying, microwave-assisted drying, infrared drying, vacuum drying, spray drying, and oven drying. Based on the evaluation of multiple studies, it can be inferred that these drying methods have the potential to contribute to low drying performance, high operational costs, and strong environmental impact. Moreover, they can affect the nutritional value of macronutrients such as proteins, starches, gums, and dietary fibers present in foods, the integrity of the food structures, and their functional properties. Understanding the correlation between the drying technique used and the functional and nutritional attributes of macromolecules will help to provide better insight into the importance of the different drying methods. Optimization of the operational parameters of the different drying methods could be vital and needs to be evaluated to avoid the degradation of the proteins and carbohydrates and the loss of their properties

Afatinib and Temozolomide Combination Inhibits Tumorigenesis by Targeting EGFRvIII-cMet Signaling in Glioblastoma Cells

BACKGROUND: Glioblastoma (GBM) is an aggressive brain tumor with universal recurrence and poor prognosis. The recurrence is largely driven by chemoradiation resistant cancer stem cells (CSCs). Epidermal growth factor receptor (EGFR) and its mutant EGFRvIII are amplified in ~ 60% and ~ 30% of GBM patients, respectively; however, therapies targeting EGFR have failed to improve disease outcome. EGFRvIII-mediated cross-activation of tyrosine kinase receptor, cMET, regulates GBM CSC maintenance and promote tumor recurrence. Here, we evaluated the efficacy of pan-EGFR inhibitor afatinib and Temozolomide (TMZ) combination on GBM in vitro and in vivo. METHODS: We analyzed the effect of afatinib and temozolomide (TMZ) combination on GBM cells U87MG and U251 engineered to express wild type (WT) EGFR, EGFRvIII or EGFRvIII dead kinase, CSCs isolated from U87 and U87EGFRvIII in vitro. The therapeutic utility of the drug combination was investigated on tumor growth and progression using intracranially injected U87EGFRvIII GBM xenografts. RESULTS: Afatinib and TMZ combination synergistically inhibited the proliferation, clonogenic survival, motility, invasion and induced senescence of GBM cells compared to monotherapy. Mechanistically, afatinib decreased U87EGFRvIII GBM cell proliferation and motility/invasion by inhibiting EGFRvIII/AKT, EGFRvIII/JAK2/STAT3, and focal adhesion kinase (FAK) signaling pathways respectively. Interestingly, afatinib specifically inhibited EGFRvIII-cMET crosstalk in CSCs, resulting in decreased expression of Nanog and Oct3/4, and in combination with TMZ significantly decreased their self-renewal property in vitro. More interestingly, afatinib and TMZ combination significantly decreased the xenograft growth and progression compared to single drug alone. CONCLUSION: Our study demonstrated significant inhibition of GBM tumorigenicity, CSC maintenance in vitro, and delayed tumor growth and progression in vivo by combination of afatinib and TMZ. Our results warrant evaluation of this drug combination in EGFR and EGFRvIII amplified GBM patients

Autosomal dominant inheritance with variable penetrance in primary familial and congenital polycythemia: A family tree

Primary familial and congenital polycythemia is a rare congenital disorder with only one case ever reported from Indian Subcontinent. Here, we are reporting an entire family inflicted with primary familial and congenital polycythemia, first ever of its kind from Indian subcontinent. We are of firm belief that our report would create awareness among medical fraternity in India about this under reported disorder

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.Methods:Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using 99 Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.Results:Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC 24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.Conclusion:Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.Fil: Sarduy, M. R.. Medical-surgical Research Center; CubaFil: García, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Coca, M. A.. Clinical Investigation Center; CubaFil: Perera, A.. Clinical Investigation Center; CubaFil: Torres, L. A.. Clinical Investigation Center; CubaFil: Valenzuela, C. M.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Baladrón, I.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Solares, M.. Hospital Materno Ramón González Coro; CubaFil: Reyes, V.. Center For Genetic Engineering And Biotechnology Havana; CubaFil: Hernández, I.. Isotope Center; CubaFil: Perera, Y.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Martínez, Y. M.. Medical-surgical Research Center; CubaFil: Molina, L.. Medical-surgical Research Center; CubaFil: González, Y. M.. Medical-surgical Research Center; CubaFil: Ancízar, J. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Prats, A.. Clinical Investigation Center; CubaFil: González, L.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Casacó, C. A.. Clinical Investigation Center; CubaFil: Acevedo, B. E.. Centro de Ingeniería Genética y Biotecnología; CubaFil: López Saura, P. A.. Centro de Ingeniería Genética y Biotecnología; CubaFil: Alonso, Daniel Fernando. Universidad Nacional de Quilmes; ArgentinaFil: Gómez, R.. Elea Laboratories; ArgentinaFil: Perea Rodríguez, S. E.. Center For Genetic Engineering And Biotechnology Havana; Cuba. Centro de Ingeniería Genética y Biotecnología; Cub

GDF15 Promotes Prostate Cancer Bone Metastasis and Colonization Through Osteoblastic CCL2 and RANKL Activation

Bone metastases occur in patients with advanced-stage prostate cancer (PCa). The cell-cell interaction between PCa and the bone microenvironment forms a vicious cycle that modulates the bone microenvironment, increases bone deformities, and drives tumor growth in the bone. However, the molecular mechanisms of PCa-mediated modulation of the bone microenvironment are complex and remain poorly defined. Here, we evaluated growth differentiation factor-15 (GDF15) function using in vivo preclinical PCa-bone metastasis mouse models and an in vitro bone cell coculture system. Our results suggest that PCa-secreted GDF15 promotes bone metastases and induces bone microarchitectural alterations in a preclinical xenograft model. Mechanistic studies revealed that GDF15 increases osteoblast function and facilitates the growth of PCa in bone by activating osteoclastogenesis through osteoblastic production of CCL2 and RANKL and recruitment of osteomacs. Altogether, our findings demonstrate the critical role of GDF15 in the modulation of the bone microenvironment and subsequent development of PCa bone metastasis

Blocking c-MET/ERBB1 Axis Prevents Brain Metastasis in ERBB2+ Breast Cancer

Brain metastasis (BrM) remains a significant cause of cancer-related mortality in epidermal growth factor receptor 2-positive (ERBB2+) breast cancer (BC) patients. We proposed here that a combination treatment of irreversible tyrosine kinase inhibitor neratinib (NER) and the c-MET inhibitor cabozantinib (CBZ) could prevent brain metastasis. To address this, we first tested the combination treatment of NER and CBZ in the brain-seeking ERBB2+ cell lines SKBrM3 and JIMT-1-BR3, and in ERBB2+ organoids that expressed the c-MET/ERBB1 axis. Next, we developed and characterized an orthotopic mouse model of spontaneous BrM and evaluated the therapeutic effect of CBZ and NER in vivo. The combination treatment of NER and CBZ significantly inhibited proliferation and migration in ERBB2+ cell lines and reduced the organoid growth in vitro. Mechanistically, the combination treatment of NER and CBZ substantially inhibited ERK activation downstream of the c-MET/ERBB1 axis. Orthotopically implanted SKBrM3+ cells formed primary tumor in the mammary fat pad and spontaneously metastasized to the brain and other distant organs. Combination treatment with NER and CBZ inhibited primary tumor growth and predominantly prevented BrM. In conclusion, the orthotopic model of spontaneous BrM is clinically relevant, and the combination therapy of NER and CBZ might be a useful approach to prevent BrM in BC

Control of bacterial nitrate assimilation by stabilization of G-quadruplex DNA

Here we present a chemical-biology study in the model soil bacterium Paracoccus denitrificans, where we show ligand-specific control of nitrate assimilation. Stabilization of a G-quadruplex in the promoter region of the nas genes, encoding the assimilatory nitrate/nitrite reductase system, is achieved using known quadruplex ligands and results in attenuation of gene transcription