Discoveries (Craiova, Romania)最新文献

Blood transfusions are one of the most common procedures performed in hospitalized patients. Yet, despite all of the measures taken to ensure the safety of the blood supply, there are known risks associated with transfusions, including infectious and noninfectious complications. Meanwhile, issues with blood product availability, the need for compatibility testing, and the storage and transport requirements of blood products, have presented challenges for the administration of blood transfusions. Additionally, there are individuals who do not accept blood transfusions (e.g., Jehovah's Witnesses). Therefore, there is a need to develop alternative agents that can reliably and safely replace blood. However, although there have been many attempts to develop blood substitutes over the years, there are currently no such products available that have been approved by the United States Food and Drug Administration (FDA). However, a more-recently developed hemoglobin-based oxygen carrier has shown promise in early clinical trials and has achieved the status of "Orphan Drug" under the FDA.

Over 100,000 cases of COVID-19 patients infected with the novel coronavirus SARS-COV-2 have been reported worldwide in approximately 2 months, resulting in over 3000 deaths. Potential therapeutic strategies, including remdesivir, chloroquine phosphate, abidol, lopinavir/ritonavir, plasma, antibody, vaccine and stem cells are discussed in this review. With the number of patients increasing daily, there is an urgent need for effective therapeutic intervention.

Bacterial resistance to existent antibiotherapy is a perpetual internationally-recognized problem. Year after year, there is a continuous need for novel antibacterial drugs and this research and development efforts recently resulted in few new drugs or combination of drugs proposed for the use into the clinic. This review focuses on the novel US FDA approved antibacterial agents in the last two years (2018-2019). Plazomicin, eravacycline, sarecycline, omadacycline, rifamycin (2018) and imipenem, cilastatin and relebactam combination, pretomanid, lefamulin, cefiderocol (2019) are new therapeutic options. Plazomicin aminoglycoside antibiotic targets Enterobacteriaceae infections, being mainly used for the complicated urinary tract infections. The fully synthetic fluorocycline eravacycline gained approval for the complicated intra-abdominal infections. The tetracycline-derived antibiotic sarecycline might be a useful strategy for the management of non-nodular moderate to severe acne, while the other tetracycline-derived antibiotic approved, omadacycline, may be used for the patients with acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. The already-known RNA-synthesis suppressor rifamycin is now also approved for noninvasive Escherichia Coli-caused travelers' diarrhea. Two combinatorial strategies were approved for complicated urinary tract infections, complicated intra-abdominal infections (imipenem, cilastatin and relebactam) and lung tuberculosis (pretomanid in combination with bedaquiline and linezolid). Lefamulin is a semisynthetic pleuromutilin antibiotic for community-acquired bacterial pneumonia, while cefiderocol, a cephalosporin antibiotic is the last antibacterial drug approved in 2019, for the use in complicated urinary tract infections. Despite of these new developments, there is an ongoing need and urgency to develop novel antibiotic strategies and drugs to overrun the bacterial resistance to antibiotics.

Diamond-Blackfan anemia (DBA) is a rare congenital bone marrow disorder with mutations in ribosomal protein genes. Several animal models have been developed to study the pathological mechanism of DBA. Previously, we reported that the complete knock-out of both Rpl5 and Rps24 alleles were lethal, while heterozygous Rpl5+/- and Rps24+/- mice showed normal phenotype.  To establish a more efficient mouse model for mimicking DBA symptoms, we have taken advantage of RNAi technology to generate an inducible mouse model utilizing tetracycline-induced down-regulation of Rpl5.    After two weeks of treatment with doxycycline in drinking water, a subset of treated shRNA Rpl5+/- adult mice developed mild anemia while control mice had normal complete blood counts. Similarly, treated shRNA Rpl5+/- mice developed reticulocytopenia and bone marrow erythroblastopenia. Detection of DBA symptoms in these mice make them a valuable DBA model for studying the pathological mechanism underlying DBA and for further assessment of the disease and drug testing for novel therapies.

Restrictive cardiomyopathy is the least common type of cardiomyopathy, being defined by diastolic dysfunction and often unimpaired systolic function. Restrictive cardiomyopathies can be classified as familial or non-familial. Patients with familial restrictive cardiomyopathy can develop signs and symptoms of this condition anytime from childhood to adulthood. The evolution of the disease is towards signs and symptoms of pulmonary and systemic congestion and, without treatment, there is a five-year mortality rate of approximately 30% in these patients. We discuss the case of a 43-year-old patient diagnosed with familial restrictive cardiomyopathy with positive genetic tests for mutations of MYH7 gene and ABCC9 gene, who was first hospitalized in 2011 for palpitations. The echocardiography performed in evolution showed a continuous alteration of right ventricle function, without important differences of left ventricular function.  She developed heart failure symptoms six years after diagnosis and she had seven hospitalizations in the past two years, currently with an increasing need of diuretics and persistent hepatic dysfunction. Cardiac transplantation or left ventricular assist device therapy should be considered in patients with severe heart failure symptoms and no longer effective treatment. However, elevated pulmonary vascular resistance excludes the patient from cardiac transplantation.

Antibiotic resistance is a relevant topic nowadays, representing one of the main causes of infection-related mortality and morbidity at a global level. This phenomenon is worrisome and represents an area of interest for both clinical practice and fundamental research. One important mechanism whereby bacteria acquire resistance to antibiotics and evade the immune system is by forming biofilms. It is estimated that ~80% of the bacteria producing chronic infections can form biofilms. During the process of biofilm formation microorganisms have the ability to communicate with each other through quorum sensing. Quorum sensing regulates the metabolic activity of planktonic cells, and it can induce microbial biofilm formation and increased virulence. In this review we describe the biofilm formation process, quorum sensing, quorum quenching, several key infectious bacteria producing biofilm, methods of prevention and their challenges and limitations. Although progress has been made in the prevention and treatment of biofilm-driven infections, new strategies are required and have to be further developed.

Expansion microscopy (ExM) is an emerging super-resolution imaging technology. ExM works by infusing a biological specimen with a superabsorbent hydrogel, followed by mechanical homogenization and isotropical expansion of the specimen in water. The unique and cost-effective process of ExM enables super-resolution optical imaging of sample of interest without the need to invest and use of a sophisticated microscope instrument. Here, we demonstrate that a nearly 3-fold isotropic physical expansion of E.coli fixed cells can be achieved in PBS, and the cell morphology during binary fission is clearly resolved in the expanded state, using a diffraction-limited microscope.

Fibroblast Growth Factor 23 (FGF23) is a hormone involved in phosphate metabolism. It is known that FGF23 is increased in different pathologies including chronic kidney disease, heart failure or X-linked hypophosphatemia and directly correlates with negative outcome and mortality in severe diseases. However, the role of FGF23 in cardiovascular pathologies is still under debate. This review summarizes the current knowledge about the role of FGF23 in ischemic heart diseases, such as myocardial infarction.

Biologists have long looked for ways to circumvent the physical diffraction limit of light and have developed many strategies to accomplish this. While many techniques employed to image sub-diffraction-limit structures rely on sophisticated equipment and computational methods, expansion microscopy (ExM) is unique in that it provides increase in resolution by physically expanding the sample embedded in a water-swellable hydrogel. ExM has rapidly grown in prevalence, owing to its ease of use and economic nature - all necessary reagents are commercially available, and samples may be imaged in large volume on conventional fluorescence microscopes. Here, we demonstrate the power of expansion microscopy on imaging synaptic connections onto a dopaminergic neuron, in the mouse substantia nigra pars compacta, with nanoscale resolution.

The introduction of immunotherapy as a treatment option has been a significant contributor to improving the survival rates for certain cancer patients. Notwithstanding these astonishing achievements, there are novel challenges for overstretched healthcare systems that will be required to manage the complex medical needs of a projected 34% increase in the number of cancer survivors over the next seven years. These alarming figures highlight the need for health systems to strengthen their capacity to deliver effective digital solutions that can be scaled to support to patients with their range of medical needs. At the core of the provision of digital solutions, it appears that a need exists for a dual focus to exist whereby patients and health care system equally benefit from the introduction of services. Among the available initiatives is a cancer support program, "The Cancer Blueprint". The Cancer Blueprint has passed three stages of testing and has impressive results that shows significant potential to be a major part in the future of cancer support programs.