Frontiers in bioscience (Scholar edition)最新文献

With several medicinal and aromatic species, the Asteraceae family is one of the largest angiosperm families. The genus Warionia is represented in this family by only one species, Warionia saharae. In Moroccan traditional medicine, this species is widely used to treat gastrointestinal problems. Essential oil of this plant (EoWs) was studied for possible myorelaxant and antispasmodic activities to rationalize some of the traditional uses. In this investigation, hydrodistillation was used to obtain the essential oil from the aerial part of the dry plant extract (EoWs), which was then analyzed using gas chromatography coupled to mass spectrometry (GC/MS). The major compounds identified in the EoWs are nerolidyl acetate (21.44%), β-Eudesmol (19.47%), linalool (16.48%), 1-terpinene-4-ol (10.93%), and cineole (5.34%). EoWs is relatively safe in the case of acute intake up to 2 g/kg body weight of albino mice. The effect of EoWs on intestinal relaxation was investigated using rabbit and rat jejunal smooth muscle. We have noticed that EoWs produce a myorelaxation on basal rabbit jejunum's contractions in a concentration-dependent manner with a maximal effect at 30 μg/mL. This myorelaxation was not dependent on adrenergic receptors. When the rat jejunums were pre-contracted with 25 mM KCl or 10 μM Carbachol (CCh), EoWs had an antispasmodic action with an IC50 values of 15.76 ± 0.37 and 12.04 ± 0.30 μg/mL, respectively. Preliminary results showed that it is probable that our plant might act directly through the NO and guanylate cyclase signaling pathway and on muscarinic but not nicotinic receptors. The results reveal that the Essential oil of W. saharae appears to have an impact on intestinal relaxation in vitro conditions. This finding lends credence to the traditional usage of this plant to treat intestinal disorders.

The role of Achromobacter species in lung disease remains unclear. The aim of this study was to characterize Achromobacter isolated from persons with cystic fibrosis and from other clinical samples. Whole genome sequences from 101 Achromobacter isolates were determined (81 from patients with cystic fibrosis and 20 from other patients) and analysed. Taxonomic analysis showed nine species including two putative novel species. Thirty-five novel sequence types were present. The most active agent was co-trimoxazole followed by imipenem, but Minimal Inhibitory Concentrations (MICs) were high. Acquired antibiotic resistance genes were rare. Their presence did not correlate with minimal inhibitory concentrations suggesting that other mechanisms are involved. Genes for proposed virulence factors were present in only some isolates. Two putative novel species were identified. The putative virulence properties of Achromobacter involved in infections are variable. Despite the high MICs, acquired resistance genes are uncommon.

The enzymes that belong to the aldehyde dehydrogenase family are expressed in a variety of cells; yet activity of their main members characterizes stem cells, both normal and malignant. Several members of this family perform critical functions in stem cells, in general, and a few have been shown to have key roles in malignant tumors and their recurrence. In particular, ALDH1A1, which localizes to the cytosol and the nucleus, is an enzyme critical in cancer stem cells. In acute myeloid leukemia (AML), ALDH1A1 protects leukemia-initiating cells from a number of antineoplastic agents, and proves vital for the establishment of human AML xenografts in mice. ALDH2, which is located in mitochondria, has a major role in alcohol metabolism by clearing ethanol-derived acetaldehyde. Haematopoietic stem cells require ALDH2 for protection against acetaldehyde, which can cause damage to DNA, leading to insertions, deletions, chromosomal rearrangements, and translocations. Mutations compromise stem cell function, and thereby threaten blood homeostasis. We review here the potential of targeting the enzymatic activity of aldehyde dehydrogenases in acute leukemia.

Cardiac magnetic resonance has become a reliable imaging modality providing structural and functional data, and fundamental information about tissue composition. Cardiac magnetic resonance imaging with late gadolinium enhancement, T1-mapping, T2-mapping, T2*-imaging, and extracellular volume, has proved to be a valuable tool in investigating the etiology of heart failure. Such analysis is helpful for the diagnostic evaluation of both ischemic and non-ischemic cardiomyopathies. As primary heart muscle diseases, the ability to characterize the myocardial substrate is essential. Determining the heart failure etiology is fundamental and has implications regarding the prognosis prediction and best treatment. Investigation in cardiac magnetic resonance in heart failure patients has grown in the past decade, and the true value of this imaging modality to detect early disease likely remains underestimated. This review describes the importance of cardiac magnetic resonance for the diagnosis and prognosis of non-ischemic cardiomyopathies, particularly hypertrophic, infiltrative, and arrhythmogenic cardiomyopathies.

Tuberculosis (TB) and Coronavirus Disease-19 (COVID-19) infection are two respiratory diseases that are of particular concern epidemiologically. Tuberculosis is one of the oldest diseases recorded in the history of mankind dating back thousands of years. It is estimated that approximately one quarter of the world's population is infected with latent Mycobacterium tuberculosis (LTBI). This contrasts with COVID-19, which emerged in late 2019. Data continues to accumulate and become available on this pathogen, but the long-term side effect of fibrotic damage in COVID-19 patients evokes parallels between this novel coronavirus and its ancient bacterial affiliate. This similarity as well as several others may incite inquiries on whether coinfection of individuals with latent TB and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lead to excessive fibrosis in the lungs and thus the emergence of an active TB infection. While it is well understood how TB leads to structural and immunological lung complications including granuloma formation, fibrosis, and T cell exhaustion, less is known about the disease course when coinfection with SARS-CoV-2 is present. Past and present research demonstrate that IL-10, TNF-α, IFN class I-III, TGF-β, IL-35, and Regulatory T cells (T-regs) are all important contributors of the characteristics of host response to mycobacterium tuberculosis. It has also been noted with current research that IL-10, TNF-α, IFN class I, II, and III, TGF-β, ACE-2, and T-regs are also important contributors to the host response to the SARS-CoV-2 virus in different ways than they are to the TB pathogen. Both pathogens may lead to an unbalanced inflammatory immune response, and together a shared dysregulation of immune response suggests an increased risk of severity and progression of both diseases. We have reviewed 72 different manuscripts between the years 1992 and 2021. The manuscripts pertaining to the SARS-COV-2 virus specifically are from the years 2020 and 2021. Our literature review aims to explore the biomolecular effects of these contributors to pathogenicity of both diseases along with current publications on TB/COVID-19 coinfection, focusing on the pathogenicity of SARS-CoV-2 infection with both latent and active TB, as well as the challenges in treating TB during the COVID-19 pandemic. The compiled material will then aid the latticework foundation of knowledge for future research leading to a hopeful improved system of therapeutic strategies for coinfection.

We aimed to compare the predictive value of different inflammatory markers in renal cell carcinoma (RCC). Four hundred ninety-five patients treated with nephrectomy for primary localized or locally advanced RCC between 2010 and 2018 were included in the retrospective analysis. The median follow-up for the entire cohort was 48 months. Based on the preoperative laboratory measurements, patients with higher neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), neutrophil/erythrocyte ratio (NER), derived neutrophil/lymphocyte ratio (dNLR), and lower lymphocyte/monocyte ratio (LMR) and hemoglobin/platelet ratio (HPR) had worse cancer-specific survival (CSS). In the multivariate analysis tumour stage, grade, age and high SIRI constituted independent factors predicting CSS. The model including SIRI values achieved C-index 0.903 (alternative multivariate models with SII and NLR 0.902 and 0.890, respectively). Age, tumour grade and high NER (or high SIRI/ SII in alternative models) were prognostic for overall survival. Markers of systemic inflammation might provide additional prognostic information (especially SIRI, SII, NLR and NER) and further increase the predictive accuracy of available models in localized and locally advanced renal cell carcinoma. For the first time, we show the prognostic value of neutrophil-to-erythrocyte ratio, which constitutes an independent risk factor of overall survival.

Recent studies provide evidence that similar to early-stage Parkinson's disease, depression is a neurodegenerative disease characterized by the degeneration of monoamine axons. The major difference between the two disorders is that the symptoms of depression become evident without loss of monoamine neurons, while the motor symptoms of Parkinson's disease appear after loss of the cell body. Given that the axonal degeneration of monoamine neurons underlies the pathophysiology of neurological (Parkinson's disease) and neuropsychiatric (depression) diseases, axonal impairment of monoamine neurons is thought to also occur in schizophrenia and bipolar disorder and play a significant role in the pathophysiology of these mental illnesses. The positive symptoms of schizophrenia and manic symptoms of bipolar disorder are known to occur in hyper-monoaminergic states, opposite to depressive symptoms, negative/cognitive symptoms of schizophrenia, and motor disorders of Parkinson's disease, all occurring in hypo-monoaminergic states. Since monoamine axons have the capacity to spontaneously regenerate or sprout in response to damage in the adult brain and sometimes show hyperinnervation due to excessive regeneration/sprouting beyond normal levels, it is possible that schizophrenia and bipolar disorder are disorders that include excessive regeneration/sprouting of monoamine axons leading to hyper-monoaminergic states. Together, based on accumulating data from animal and human studies, the pathophysiology of schizophrenia, major depression, and bipolar disorder is summarized as follows: The degeneration of monoamine axons is associated with the negative and cognitive symptoms of schizophrenia, major and bipolar depression, while hyper-regeneration/sprouting of monoamine axons underlies the positive symptoms of schizophrenia and bipolar mania. The integrated understanding of schizophrenia, major depression, and bipolar disorder as monoamine axon disorder will open the door to the development of new diagnosis and treatment methods for major mental illnesses as well as early-stage Parkinson's disease.

While the primary purpose of radiotherapy (RT) is the elimination of cancer cells by inducing DNA-damage, considerable evidence emerges that anti-neoplastic effects extend beyond mere tumor cell killing. These secondary effects are based on activation of dendritic cells (DCs) via induction of antitumoral immune reactions. However, there is an ongoing debate whether or not irradiation of the DCs themselves may negatively affect their maturation and functionality. Human monocytes were irradiated with different absorbed doses (1 × 15 Gy relative biological effectiveness (RBE), 5 × 2 Gy (RBE), 1 × 0.5 Gy (RBE)) with photons, protons and carbon ions. Differentiation and maturation of DCs were assessed by staining of corresponding cell surface molecules and functional analysis of irradiated DCs was based on in vitro analysis of phagocytosis, migration and IL-12 secretion. Irradiation of CD14-positive DCs did not alter surface phenotypes of immature DCs and mature DCs. Not only differentiation, but also functionality of immature DCs regarding phagocytosis, migration and IL-12 secretion capacity was not negatively influenced through RT with photons, protons or carbon ions as well as with different dose levels. After proton irradiation migratory capacity of immature DCs was increased. Our experiments reveal that phenotypic maturation of DCs remains unchanged after RT with different fractionations and after irradiation with particle therapy. Unaffected functionality (phagocytosis, migration and cytokine secretion) after RT of DCs indicated possible persistent potential for inducing adaptive immune response. Additional effects on the immunogenic potential of DCs will be investigated by further functional assays.

The approach to the study of autophagy has been undergoing considerable change lately: from investigations of the protein components of autophagic machinery to its regulation at different molecular levels. Autophagy is being examinated not only as a separated degradative process per se in cells but as an executor mechanism of certain signaling pathways that converge on it, being activated under specific conditions. Additionally, autophagy is beginning to be observed as a key integral part of cellular reprogramming, the transition from one phenotypic state to another associated with rapid degradation of the previous proteostasis. Macrophages and microglia demonstrate a diversity of phenotypes reflecting their effective capability to phenotypic plasticity. Therefore, understanding the role of autophagy in macrophage and microglia functions needs to be addressed. In this review, we focus on autophagy as a fundamental intracellular process underlying macrophages and microglia polarization.

Among central nervous system (CNS) infections (e.g., meningitis, brain abscess, ventriculitis, transverse myelitis), those caused by Staphylococcus aureus (SA) are particularly challenging both in management and treatment, with poor clinical outcomes and long hospital stay. It has been estimated that SA is responsible for around 1%-7% of meningitis (up to 19% in healthcare-associated meningitis). Recent neurosurgical procedures and immunocompromisation are major risk factors for SA CNS infections. Hand hygiene, surveillance nasal swabs and perioperative prophylaxis are crucial points for effective SA infections prevention. In case of SA-CNS infections, pending microbiological results, anti-methicillin-resistant SA (MRSA) antibiotic, with good CNS penetration, should be included, with prompt de-escalation as soon as MRSA is ruled out. Consultation with an expert in antimicrobial therapy is recommended as well as prompt source control when feasible. In this narrative review, we reviewed current literature to provide practical suggestions on diagnosis, prevention, management, and treatment of SA CNS infections.