Discoveries (Craiova, Romania)最新文献

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.

Background: This study was designed to assess right ventricular systolic function in cancer patients.

Methods and results: 68 consecutive patients receiving potentially cardiotoxic agents were followed for 6 months in a single-center, observational, cohort-study. Left ventricle and free-wall right ventricular longitudinal strain were analyzed prior and after 6 months of treatment, using a vendor-independent software, together with left ventricle ejection fraction, tricuspid annulus plane systolic excursion and right ventricular fractional area change. Cancer therapy-related cardiac dysfunction was defined as a left ventricle ejection fraction drop of >10% to <53%. Both left ventricle ejection fraction (59±7% vs. 55±8%, p<0.0001) and left ventricle longitudinal strain (-19.7±2.5% vs. -17.1±2.6%, p<0.0001) were reduced at follow up, along with free-wall right ventricular longitudinal strain (-24.9±4.5% vs. -21.6±4.9%, p<0.0001). Cancer therapy-related cardiac dysfunction was detected in 20 patients (29%). In 15 out of these 20 patients (75%), a concomitant relative reduction in free-wall right ventricular longitudinal strain magnitude by 17±7% was detected. Moreover, there was a significant correlation between left ventricle and free-wall right ventricular longitudinal strain at follow-up examinations (r=0.323, p<0.0001). A relative drop of right ventricular longitudinal strain >17% had a sensitivity of 55% and a specificity of 70% (AUC=0.75, 0.7-0.8, 95% CI) to identify patients with cancer treatment related cardiac dysfunction. Neither tricuspid annulus plane systolic excursion (24±5 vs. 23±4 mm, p=0.07), nor right ventricular fractional area change (45±8% vs. 44±7%, p=0.6) showed any significant change between examinations.

Conclusions: Longitudinal strain analysis allows the identification of subclinical right ventricular dysfunction appearing in the course of cancer treatment when conventional indices of right ventricular dysfunction function are unaffected.

Brain metastases are about ten times more frequent than a brain primary tumor, being present in 20-40% of adults with systemic cancer. Together with lung cancer and breast cancer, skin cancers such as melanoma are top primary tumors which metastasizes to the brain. Advanced melanoma is well known for its propensity to metastasize to the brain, with 80% of patients presenting brain metastasis at the autopsy. However, current therapies are not very efficient and brain metastases are in most of the cases lethal. Treatment of melanoma brain metastases with surgery and/or radiation therapy results in a median overall survival of only about four months after diagnosis. New immunotherapies such as targeted or immunomodulatory drugs, many in clinical trials, have shown promise, with some immunomodulatory drugs being able to at least double the overall survival rates for patients with melanoma brain metastases. This review focuses on the recent advances and future potential of using immunotherapy, such as the newly developed immunomodulatory drugs, for melanoma brain metastases therapy. Immunomodulatory drugs bring a great promise as new tools for melanoma treatment in particular and for the treatment of other types of malignancies in general.

Despite the increasing prevalence and acceptance of the medical cannabis use among the general public, the evidence required by physicians to use cannabis as a treatment is generally lacking. Research on the health effects of cannabis and cannabinoids has been limited worldwide, leaving patients, health care professionals, and policymakers without the evidence they need to make sound decisions regarding the use of cannabis and cannabinoids. This case study outlines an intervention that involved a patient integrating medical cannabis into her treatment to better manage a generalized anxiety disorder and the debilitating symptoms of vertigo. This case demonstrates how the patient drastically improved her quality of life and reinforces the need for more rigorous testing on the use of medical cannabis to support patients and better manage the symptoms associated with their medical conditions.

1 in 8 women will be affected by breast cancer, which is the most diagnosed malignancy among women. Although breast cancer was regarded as "immunologically cold", recent studies demonstrate that immunotherapy can be successful employed in combination regimens for the treatment of triple negative breast cancer, an aggressive type of breast cancer without many treatment options available. In March 2019, the US Food and Drug Administration granted accelerated approval for the first immunotherapy-based regimen comprising atezolizumab in combination with protein-bound paclitaxel for patients with advanced metastatic TNBC, expressing programmed cell death-ligand 1 (PD-L1) and without previous systemic treatment for metastatic disease. This immunotherapy-based regimen is not only a promising therapy for the TNBC patients, but it also represents an inspiring proof of concept for the development of more efficient advanced immunotherapy-based strategies for breast cancer treatment in the future.

Breast cancer is the second most commonly diagnosed cancer, being one of the main health issues that needs to be addressed worldwide. New therapies have led to a remarkable increase in survival rates, which is unfortunately overshadowed by their negative impact on cardiac structure and function in disease-free patients. Since anthracyclines and trastuzumab cause the most undesired outcome in breast cancer patients - cardiac-related mortality, they have been widely studied. However, other therapies (such as hormonal therapy, tyrosine kinase inhibitors, anti-VEGF drugs etc.) can also affect the cardiovascular system and lead to ischemia, hypertension or vascular thromboembolism. Even though excessive research has been conducted in thepast decades, there are still no guidelines regarding the most adequate methods neither to detect and prevent severe cardiotoxicity that can finally lead to heart failure and ultimately death nor for the further management of patients after cardiotoxicity is detected. Biomarkers of ischemia (troponins T and I) and of overload (BNP and NT-proBNP) in association with periodic echocardiographies (assessment of the global longitudinal strain) are two of the most important means used by physicians in the evaluation of cardiac disease in this group of patients. Given that no internationally accepted guidelines for screening and surveillance of different populations exist, the cardio-oncology team is crucial in the management of these patients, their collaboration resulting in individualized treatment regimens. After careful evaluation of different variables (treatment effects, malignancy status, and the patient's pre-existing conditions), a decision is made to either reduce the dosage or rate of administration, change the medication or interrupt the treatment and initiate the cardioprotective therapeutic associations. Consequently, it is an absolute necessity the development of customized treatment guidelines and the conduction of multiple clinical studies in order to demonstrate their effect on long-term survival.

Skeletal muscle tissue has inherent capacity for regeneration in response to minor injuries. However, in the case of severe trauma, tumor ablations, or in congenital muscle defects, these myopathies can cause irreversible loss of muscle mass and function, a condition referred to as volumetric muscle loss (VML). The natural muscle repair mechanisms are overwhelmed, prompting the search for new muscle regenerative strategies, such as using biomaterials that can provide regenerative signals to either transplanted or host muscle cells. Recent studies involve the use of suitable biomaterials which may be utilized as a template to guide tissue reorganization and ultimately provide optimum micro-environmental conditions to cells. These strategies range from approaches that utilize biomaterials alone to those that combine materials with exogenous growth factors, and ex vivo cultured cells. A number of scaffold materials have been used in the development of grafts to treat VML. In this brief review, we outline the natural skeletal regeneration process, available treatments used in the clinic for muscle injury and promising tissue bioengineering and regenerative approaches for muscle loss treatment.