Frontiers in bioscience (Scholar edition)最新文献

Obesity and osteoporosis are global health problems characterized by high rates of prevalence and mortality due to complications. As people with visceral obesity age, the adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) increases, and adipocytes become the predominant stromal cells in the bone marrow microenvironment, which hinders the physiological regeneration and mineralization of bone tissue. Primary and secondary osteoporosis remain severe progressive diseases. Both osteoporosis and obesity are associated with microRNAs (miRNAs) that induce adipogenesis and osteoresorption. This review presents analyses of the roles and clinical potential of miRNAs in the epigenetic control of BMSC differentiation and the formation and function of osteoclasts in osteoporosis with and without obesity. Understanding the fine-tuned regulation of the expression of genes critical for the balance of osteogenesis/osteolysis processes may provide hope for the development of effective and safe osteoporosis therapies in the future.

Melissa officinalis L. is a plant of the Lamiaceae family known in numerous countries for its medicinal activities. This plant has been used since ancient times to treat different disorders, including gastrointestinal, cardiovascular, neurological, psychological conditions. M. officinalis contains several phytochemicals such as phenolic acids, flavonoids, terpenoids, and many others at the basis of its pharmacological activities. Indeed, the plant can have antioxidant, anti-inflammatory, antispasmodic, antimicrobial, neuroprotective, nephroprotective, antinociceptive effects. Given its consolidated use, M. officinalis has also been experimented with clinical settings, demonstrating interesting properties against different human diseases, such as anxiety, sleeping difficulties, palpitation, hypertension, depression, dementia, infantile colic, bruxism, metabolic problems, Alzheimer's disease, and sexual disorders. As for any natural compound, drug, or plant extract, also M. officinalis can have adverse effects, even though the reported events are very rare and the plant can be considered substantially safe. This review has been prepared with a specific research strategy, interrogating different databases with the keyword M. officinalis. Moreover, this work analyzes the properties of this plant updating currently available literature, with a special emphasis on human studies.

Prostate cancer is one of the most common and socially significant cancers among men. The aim of this study was to identify significant changes in the expression of exosomal miRNAs associated with an increase in the level of prostate specific antigen in castration-resistant prostate cancer during therapy and to evaluate them as potential prognostic markers for this category of disease. High-throughput miRNA sequencing was performed on 49 blood plasma samples taken from 11 Russian patients with castration-resistant cancer during therapy. Bioinformatic analysis of the obtained miRNA-seq data was carried out. Additionally, miRNA-seq data from the PRJNA562276 project were analyzed to identify exosomal miRNAs associated with castration-resistant prostate cancer. We found 34 differentially expressed miRNAs associated with the progression of castration-resistant prostate cancer during therapy in Russian patients. It was also shown that hsa-miRNA-148a-3p expression can serve as a potential prognostic marker. We found the exosomal miRNA expression signature associated with castration-resistant prostate cancer progression, in particular on the Russian patient cohort. Many of these miRNAs are well-known players in either oncogenic transformation or tumor suppression. Further experimental studies with extended sampling are required to validate these results.

Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.

The COVID-19 pandemic has provided an opportunity for repurposing of drugs, including complex, natural drugs, to meet the global need for safe and effective antiviral medicines which do not promote multidrug resistance nor inflate medical costs. The author herein describes his own repurposing of herbal tinctures, previously prepared for oncology, into a possibly synergistic, anti-COVID 41 "herb" formula of extracts derived from 36 different plants and medicinal mushrooms. A method of multi-sample in vitro testing in green monkey kidney vero cells is proposed for testing the Hypothesis that even in such a large combination, antiviral potency may be preserved, along with therapeutic synergy, smoothness, and complexity. The possibility that the formula's potency may improve with age is considered, along with a suitable method for testing it. Collaborative research inquiries are welcome.

The search for new antimicrobials is essential to address the worldwide issue of antibiotic resistance. The present work aimed at assessing the antimicrobial activity of Aesculus hippocastanum L. (horse chestnut) bark against bacteria involved in urinary tract infections (UTIs). Bioactive compounds were extracted from A. hippocastanum bark using water and ethanol as solvents. The extracts were tested against 10 clinical uropathogenic strains including five Gram-positive and five Gram-negative bacteria. Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 25922 were used as reference bacteria. The susceptibility to antibiotics was assessed using the Kirby Bauer disc diffusion method and the antibacterial activity of the extracts was evaluated using the well diffusion method. The Minimum inhibitory concentration (MIC) and the minimum bactericidal concentrations (MBC) were asseded by the microdilution method. A. hippocastanum bark possessed a dry matter content of 65.73%. The aqueous extract (AE) and ethanolic extract (EE) showed a volume yield of 77.77% and 74.07% (v/v), and a mass yields of 13.4% and 24.3% (w/w) respectively. All the bacteria were susceptible to amoxiclav, imipenem and ceftriaxone but the clinical strains were resistant to at least one antibiotic. Kocuria rizophilia 1542 and Corynebacterium spp 1638 were the most resistant bacteria both with multidrug resistance index of 0.45. Except AE on Proteus Mirabilis 1543 and Enterococcus faecalis 5960 (0 mm), both AE and EE were active against all the microorganisms tested with inhibition diameters (mm) which ranged from 5.5-10.0 for AE and 8.0-14.5 for EE. The MICs of EEs varied from 1-4 mg/mL while those of AEs varied from 4-16 mg/mL. The ethanolic extracts (EE) were overall more active than the aqueous ones. The A. hippocastanum bark extracts had overall weak antibacterial activity (MIC ≥0.625 mg/mL) and bacteriostatic potential (MBC/MIC ≥16) on both Gram-positive and Gram-negative bacteria.

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.