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Drug Repurposing Approaches towards Defeating Multidrug-Resistant Gram-Negative Pathogens: Novel Polymyxin/Non-Antibiotic Combinations.

Multidrug-resistant (MDR) Gram-negative pathogens remain an unmet public health threat. In recent times, increased rates of resistance have been reported not only to commonly used antibiotics, but also to the last-resort antibiotics, such as polymyxins. More worryingly, despite the current trends in resistance, there is a lack of new antibiotics in the drug-discovery pipeline. Hence, it is imperative that new strategies are developed to preserve the clinical efficacy of the current antibiotics, particularly the last-line agents. Combining conventional antibiotics such as polymyxins with non-an

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… The Mobile Colistin Resistance Gene, mcr-1.1, Is Carried on IncX4 Plasmids in Multidrug Resistant E. coli Isolated from Rainbow Trout Aquaculture Microorganisms 2020 8 1636 10.3390/microorganisms8111636 33113918 PMC7690709 72. Gao R. Hu Y. Li Z. Sun J. Wang Q. Lin J. Ye H. Liu F. Srinivas S. Li D. …

Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes.

BackgroundCancer patients often develop the potentially debilitating condition of anaemia. Numerous controlled studies indicate that erythropoiesis-stimulating agents (ESAs) can raise haemoglobin levels and reduce transfusion requirements in anaemic cancer patients receiving chemotherapy. To evaluate recent safety concerns regarding ESAs, we carried out a meta-analysis of controlled ESA oncology trials to examine whether ESA use affects survival, disease progression and risk of venous-thromboembolic events.MethodsThis meta-analysis included studies from the 2006 Cochrane meta-analysis, studies

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… Amgen Inc., Thousand Oaks, CA Auerbach M, Ballard H, Trout JR, McIlwain M, Ackerman A, Bahrain H, Balan S, Barker L, Rana J (2004) Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial …

Imaging for Plasma Cell Dyscrasias: What, When, and How?

Imaging plays a vital role in the diagnosis, response assessment, and follow-up of patients with plasma cell bone disease. The radiologic diagnostic paradigm has thus far evolved with developing technology and availability of better imaging platforms; however, the skewed availability of these imaging modalities in developed vis-à-vis the developing countries along with the lack of uniformity in reporting has led to a consensus on the imaging criteria for diagnosing and response assessment in plasma cell dyscrasia. Therefore, it is imperative for not only the radiologists but also the treating

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… McDonald RJ, Trout AT, Gray LA, Dispenzieri A, Thielen KR, Kallmes DF. Vertebroplasty in Multiple Myeloma: Outcomes in a Large Patient Series. Am J Neuroradiol (2008) 29(4):642–8. doi: 10.3174/ajnr.A0918 62. Baur A, Huber A, Ertl-Wagner B, Dürr R, Zysk S, Arbogast S, et al. …

Machine Learning Approaches in Diagnosis, Prognosis and Treatment Selection of Cardiac Amyloidosis.

Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thou

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… Buck P.M., Kumar S., Wang X., Agrawal N.J., Trout B.L., Singh S.K. Computational methods to predict therapeutic protein aggregation. Methods Mol. Biol. 2012;899:425–451. doi: 10.1007/978-1-61779-921-1_26. 151. Buck P.M., Kumar S., Singh S.K. …

Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengin

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… Binkley N., Bolognese M., Sidorowicz-Bialynicka A., Vally T., Trout R., Miller C., Buben C.E., Gilligan J.P., Krause D.S., Oral Calcitonin in Postmenopausal Osteoporosis I. …

Нацеливаюсь на гормональное лечение мозга в менопаузе.

Эстрогены являются нейрозащитными, и менопауза может способствовать нейродегенерации. Эстриол преимущественно связывает бета-рецептор эстрогена (ERβ) в мозге для обеспечения нейрозащиты. Ранее пероральный эстриол повышал скорость когнитивной обработки и уменьшил атрофию коры головного мозга в месяц лечения twelve в случае женщин с множественным склерозом (МС). В данном случае лечение с помощью волдыря, предназначенного для здоровых менопаузальных женщин, содержащих эстриол и прогестерон (Pearlpak), оценивалось с точки зрения его воздействия на когнитивные симптомы, характерные для домена, в ря

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… . & Trout, A. L. Estrogen receptor-alpha gene expression in the cortex: sex differences during development and in adulthood. Horm. Behav. 59 , 353–357. 10.1016/j.yhbeh.2010.08.004 (2011). 25. Mitra, S. W. et al. …

Chemokines in COPD: From Implication to Therapeutic Use.

: Chronic Obstructive Pulmonary Disease (COPD) represents the 3rd leading cause of death in the world. The underlying pathophysiological mechanisms have been the focus of extensive research in the past. The lung has a complex architecture, where structural cells interact continuously with immune cells that infiltrate into the pulmonary tissue. Both types of cells express chemokines and chemokine receptors, making them sensitive to modifications of concentration gradients. Cigarette smoke exposure and recurrent exacerbations, directly and indirectly, impact the expression of chemokines and chem

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… Trout H.H. Neves J.F. Gardner P.J. Plerixafor for the Treatment of WHIM Syndrome N. Engl. J. Med. 2019 380 163 170 10.1056/NEJMoa1808575 30625055 PMC6425947 164. Bonig H. Chudziak D. Priestley G. Papayannopoulou T. …

IL-34 в неврологическом гомеостазисе и его многогранная роль в заболеваниях центральной нервной системы.

Interleukin-34 (IL-34), лиганд для рецептора макрофажных колоний (CSF1R), играет незаменимую роль в развитии и поддержании гомеостазиса центральной нервной системы (CNS). В настоящем обзоре систематически излагаются основные механизмы, с помощью которых ось сигнала IL-34/CSF1R регулирует развитие, колонизацию и функциональную дифференциацию иммунных клеток-резидентов, включая микроглию и макрофаги, связанные с границами (BAM). Она подчеркивает свою роль в критических физиологических процессах, таких, как синаптическое обрезка, созревание нервной цепи и поддержание целостности мозгового барьера

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… Identification of IL-34 in teleost fish: differential expression of rainbow trout IL-34, MCSF1 and MCSF2, ligands of the MCSF receptor. Mol Immunol. (2013) 53:398–409. doi: 10.1016/j.molimm.2012.09.008 47. Nakamichi Y, Udagawa N, Takahashi N. IL-34 and CSF-1: similarities and differences. …

Прогресс в оказании поддержки в проведении обзора по множественным болезням, связанным с миеломой.

Множественная миелома (ММ) — неизлечимая порча плазменных клеток, характеризующаяся увеличением производства моноклонального иммуноглобулина. Пациенты с ММ подвержены высокому риску возникновения осложнений, связанных с заболеваниями. Остеолитическая болезнь костей one - из наиболее распространенных осложнений, связанных с заболеваниями, которые приводят к хронической боли и патологии скелета, что в значительной степени способствует высоким уровням заболеваемости и смертности среди пациентов с ОМ. Помимо стандартной антиММ-терапии, для улучшения качества жизни пациентов, страдающих ММ, необход

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… McDonald R., Trout A., Gray L., Dispenzieri A., Thielen K., Kallmes D. Vertebroplasty in Multiple Myeloma: Outcomes in a Large Patient Series. Am. J. Neuroradiol. 2008;29:642–648. doi: 10.3174/ajnr.A0918. 96. …

Phage Display Derived Monoclonal Antibodies: From Bench to Bedside.

Monoclonal antibodies (mAbs) have become one of the most important classes of biopharmaceutical products, and they continue to dominate the universe of biopharmaceutical markets in terms of approval and sales. They are the most profitable single product class, where they represent six of the top ten selling drugs. At the beginning of the 1990s, an in vitro antibody selection technology known as antibody phage display was developed by John McCafferty and Sir. Gregory Winter that enabled the discovery of human antibodies for diverse applications, particularly antibody-based drugs. They created c

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… Chennamsetty N, Voynov V, Kayser V, Helk B, Trout BL. Prediction of aggregation prone regions of therapeutic proteins. J Phys Chem B. (2010) 114:6614–24. 10.1021/jp911706q 96. Jain T, Sun T, Durand S, Hall A, Houston NR, Nett JH, et al. …

Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy.

Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients' quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin w

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… Chaudhuri AD, Dastgheyb RM, Yoo SW, Trout A, Talbot CC, Jr, Hao H, Witwer KW, Haughey NJ. TNFα and IL-1β modify the miRNA cargo of astrocyte shed extracellular vesicles to regulate neurotrophic signaling in neurons. Cell Death Dis. 2018;9(3):363. doi: 10.1038/s41419-018-0369-4. 125. …

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine.

Cancer causes millions of deaths each year and thus urgently requires the development of new therapeutic strategies. Nanotechnology-based anticancer therapies are a promising approach, with several formulations already approved and in clinical use. The evaluation of these therapies requires efficient in vivo models to study their behavior and interaction with cancer cells, and to optimize their properties to ensure maximum efficacy and safety. In this way, zebrafish is an important candidate due to its high homology with the human genoma, its large offspring, and the ease in developing specifi

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… Tumor suppression in triploid trout. Aquat. Toxicol. 1999;46:121–126. doi: 10.1016/S0166-445X(98)00121-0. 59. Mizgireuv I.V., Majorova I.G., Gorodinskaya V.M., Khudoley V.V., Revskoy S.Y. Carcinogenic Effect of N-Nitrosodimethylamine on Diploid and Triploid Zebrafish (Danio rerio) Toxicol. …

COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

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… Antibiotic resistance genes in freshwater trout farms in a watershed in Chile J. Environ. Qual. 48 2019 1462 1471 10.2134/jeq2018.12.0431 31589726 42 Le Bon A. Tough D.F. Links between innate and adaptive immunity via type I interferon Curr. Opin. …

Crosstalk between glucocorticoid and mineralocorticoid receptors boosts glucocorticoid-induced killing of multiple myeloma cells.

The glucocorticoid receptor (GR) is a crucial drug target in multiple myeloma as its activation with glucocorticoids effectively triggers myeloma cell death. However, as high-dose glucocorticoids are also associated with deleterious side effects, novel approaches are urgently needed to improve GR action in myeloma. Here, we reveal a functional crosstalk between GR and the mineralocorticoid receptor (MR) that plays a role in improved myeloma cell killing. We show that the GR agonist dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the

Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy.

In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct

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… infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases Cancer Chemother Pharmacol 2013 71 955 63 10.1007/s00280-013-2088-y 23377373 PMC3977741 149 Balar AV Apolo AB Ostrovnaya I Mironov S Iasonos A Trout …

Primary Osteoporosis Induced by Androgen and Estrogen Deficiency: The Molecular and Cellular Perspective on Pathophysiological Mechanisms and Treatments.

Primary osteoporosis is closely linked to hormone deficiency, which disrupts the balance of bone remodeling. It affects postmenopausal women but also significantly impacts older men. Estrogen can promote the production of osteoprotegerin, a decoy receptor for RANKL, thereby preventing RANKL from activating osteoclasts. Furthermore, estrogen promotes osteoblast survival and function via activation of the Wnt signaling pathway. Likewise, androgens play a critical role in bone metabolism, primarily through their conversion to estrogen in men. Estrogen deficiency accelerates bone resorption throug

Recent Advances in Zinc Oxide Nanoparticles (ZnO NPs) for Cancer Diagnosis, Target Drug Delivery, and Treatment.

Cancer is regarded as one of the most deadly and mirthless diseases and it develops due to the uncontrolled proliferation of cells. To date, varieties of traditional medications and chemotherapies have been utilized to fight tumors. However, their immense drawbacks, such as reduced bioavailability, insufficient supply, and significant adverse effects, make their use limited. Nanotechnology has evolved rapidly in recent years and offers a wide spectrum of applications in the healthcare sectors. Nanoscale materials offer strong potential for curing cancer as they pose low risk and fewer complica

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… Effect of zinc on viral-host interactions in a rainbow trout cell line, RTG-2 Water Res. 1971 5 703 710 10.1016/0043-1354(71)90092-3 52. Rasmussen J.W. Martinez E. Louka P. Wingett D.G. …

Tumor angiogenesis as a target for dietary cancer prevention.

Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain,

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… The best known sources of the long-chain omega-3 fatty acids—docosahexaenoic acid (DHA) and eicosapentaenoic (EPA)—are cold water oily fish such as salmon, herring, mackerel, anchovies, sardines, and trout. …

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values.

Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific database

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… Furthermore, 8-OHdG and nuclear factor-kappa B (NF-κB) immunopositivity was reported in brain tissues of rainbow trout exposed to linuron, a herbicide used widely to control grasses and annual broadleaf weeds (Topal et al., 2017 ). …