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This study reports on the development of an original, ex-vivo wounded skin culture protocol using autologous Platelet Rich Plasma (PRP) and enriched Dulbecco's Modified Eagle's Medium (DMEM). Human skin samples obtained from specimens harvested during reduction mammoplasty procedures, were injured in their central portion-to create a standard wound-and cultured under three different conditions: - enriched DMEM with saline solution in the central wound (control)- enriched DMEM with the same medium in the central wound- enriched DMEM plus 2.5% autologous PRP, with the same PRP added medium in the central wound. Morphological analysis was carried out at 0 h (T0) and on days 1, 3, 5 and 10 (T1-T3-T5-T10) using Hematoxylin and Eosin; Masson's trichrome staining; Weigert staining and Ki-67 staining to identify the skin histological features in the different experimental conditions. The combination of DMEM and PRP allowed a favorable modulation of the epithelial cells and fibroblasts proliferation, and a relevant anti-inflammatory action. PRP also demonstrated an inhibitory effect on both the collagen and elastic fibers' de-structuration and a favorable modulation of the re-organization of these fibers. The step by step histological and immune-histo-chemical regenerative effects of PRP on human skin wound repair and regeneration process was observed over a period of 10 days.
Treadmill running and tibial loading are two common modalities used to assess the role of mechanical stimulation on the skeleton preclinically. The primary advantage of treadmill running is its physiological relevance. However, the applied load is complex and multiaxial, with observed results influenced by cardiovascular and musculoskeletal effects. In contrast, with tibial loading, a direct uniaxial load is applied to a single bone, providing the advantage of greater control but with less physiological relevance. Despite the importance and wide-spread use of both modalities, direct comparisons are lacking. In this study, we compared effects of targeted tibial loading, treadmill running, and their combination on cancellous and cortical architecture in a murine model. We show that tibial loading and treadmill running differentially improve bone mass, with tibial loading resulting in thicker trabeculae and increased cortical mass, and exercise resulting in greater number of trabeculae and no cortical mass-based effects. Combination of the modalities resulted in an additive response. These data suggest that tibial loading and exercise may improve mass differentially.
Colistin is the last-resort antibiotic against lethal infections with multidrug-resistant bacterial pathogens. A rainbow coalition of mobile colistin resistance (mcr) genes raises global health concerns. Here, we describe the action and mechanism of colistin resistance imparted by MCR-4, a recently-identified member from the broader MCR family. We found that MCR-4 originates from the silenced variant of Shewanella frigidimarina via progressive evolution and forms a phylogenetically-distinct group from the well-studied MCR-1/2 family. Domain-swapping experiments further confirmed that MCR-1 and MCR-4 transmembrane and catalytic domains are not functionally-interchangeable. However, structural and functional analyses demonstrated that MCR-4 possesses a similar PE lipid substrate-recognizable cavity and exploits an almost-identical ping-pong catalysis mechanism. MCR-4 also can alleviate colistin-triggered accumulation of reactive oxygen species (ROS). Taken together, this finding constitutes a functional proof that MCR-4 proceeds in a distinct evolutionary path to fulfill a consistent molecular mechanism, resulting in phenotypic colistin resistance.
A Gram-positive, coagulase-negative, novobiocin resistant, and lithium-tolerant bacterium was isolated from Salar de Atacama. Strain LCHXa is closely related to Staphylococcus sciuri. Its genome is 3,013,090 bp long and contains 2,551 predicted protein genes. We observed 58 genes associated with stress response and 17 genes linked to osmoregulation, mainly related to glycine betaine metabolism.
Severe community-acquired pneumonia (CAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare and is usually associated with rapid progression to death. Here, we report the complete genome sequence of the MRSA strain JMUB3031, which was isolated from a patient with fatal CAP.
Parasitic infections potentially drive host's life-histories since they can have detrimental effects on host's fitness. Telomere dynamics is a candidate mechanism to underlie life-history trade-offs and as such may correlate with observed fitness reduction in infected animals. We examined the relationship of chronic infection with two genera of haemosporidians causing avian malaria and malaria-like disease with host's telomere length (TL) in a longitudinal study of free-ranging blue tits. The observed overall infection prevalence was 80% and increased with age, constituting a potentially serious selective pressure in our population. We found longer telomeres in individuals infected with a parasite causing lesser blood pathologies i.e. Haemoproteus compared to Plasmodium genus, but this only held true among males. Female TL was independent of the infection type. Our results indicate that parasitic infections could bring about other types of costs to females than to males with respect to TL. Additionally, we detected linear telomere loss with age, however a random regression analysis did not confirm significant heterogeneity in TL of first breeders and telomere shortening rates in further life.
Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined.
The unique antimicrobial mechanism of antimicrobials make them a promising substitute for antibiotics for fighting drug-resistant bacteria. Both melittin and thanatin have antimicrobial bioactivity. However, thanatin does not inhibit the growth of Staphylococcus aureus. Melittin can inhibit S. aureus and has strong hemolytic activity. In the present study, the mutant fragments of melittin and thanatin were combined by flexible peptides to form a novel hybrid peptide, which was synthesized based on the secondary and tertiary structure prediction. The hybrid peptide inhibited S. aureus with a hemolytic concentration of above 45 μmol/L and inhibition rate in SMMC-7721 cells of 19.14%. The hybrid antimicrobial peptide, which was designed by the combination of α-helix and β-lamellar antimicrobial peptides, showed that both types of peptides did not interact with each either on spatial structure or biological activities, thereby providing a novel idea for the design of artificial antimicrobial peptides.
The terms extracellular vesicles, microvesicles, oncosomes, or exosomes are often used interchangeably as descriptors of particles that are released from cells and comprise a lipid membrane that encapsulates nucleic acids and proteins. Although these entities are defined based on a specific size range and/or mechanism of release, the terminology is often ambiguous. Nevertheless, these vesicles are increasingly recognized as important modulators of intercellular communication. The generic characterization of extracellular vesicles could also be used as a descriptor of enveloped viruses, highlighting the fact that extracellular vesicles and enveloped viruses are similar in both composition and function. Their high degree of similarity makes differentiating between vesicles and enveloped viruses in biological specimens particularly difficult. Because viral particles and extracellular vesicles are produced simultaneously in infected cells, it is necessary to separate these populations to understand their independent functions. We summarize current understanding of the similarities and differences of extracellular vesicles, which henceforth we will refer to as exosomes, and the enveloped retrovirus, HIV-1. Here, we focus on the presence of these particles in semen, as these are of particular importance during HIV-1 sexual transmission. While there is overlap in the terminology and physical qualities between HIV-1 virions and exosomes, these two types of intercellular vehicles may differ depending on the bio-fluid source. Recent data have demonstrated that exosomes from human semen serve as regulators of HIV-1 infection that may contribute to the remarkably low risk of infection per sexual exposure.
Current Hi-C analysis approaches are unable to account for reads that align to multiple locations, and hence underestimate biological signal from repetitive regions of genomes. We developed and validated mHi-C, a multi-read mapping strategy to probabilistically allocate Hi-C multi-reads. mHi-C exhibited superior performance over utilizing only uni-reads and heuristic approaches aimed at rescuing multi-reads on benchmarks. Specifically, mHi-C increased the sequencing depth by an average of 20% resulting in higher reproducibility of contact matrices and detected interactions across biological replicates. The impact of the multi-reads on the detection of significant interactions is influenced marginally by the relative contribution of multi-reads to the sequencing depth compared to uni-reads, cis-to-trans ratio of contacts, and the broad data quality as reflected by the proportion of mappable reads of datasets. Computational experiments highlighted that in Hi-C studies with short read lengths, mHi-C rescued multi-reads can emulate the effect of longer reads. mHi-C also revealed biologically supported bona fide promoter-enhancer interactions and topologically associating domains involving repetitive genomic regions, thereby unlocking a previously masked portion of the genome for conformation capture studies.
Common nucleotide-binding oligomerization domain containing 2 (NOD2) gene variants have been associated with bacterial infections (BIs) in cirrhosis, in particular, spontaneous bacterial peritonitis, and mortality. Our aim was to evaluate the independent association of NOD2 variants with BI according to the decompensation stage.
Transient receptor potential ankyrin 1 (TRPA1) from tetrapod vertebrates except rodents are activated by high temperature with a relatively clear threshold. Our recent investigation suggested that a gradual heat activation without clear threshold might be a common feature for TRPA1 of fish. To approach which animal first acquires TRPA1 as a threshold detector instead of a gradual heat sensor, here, we focused on TRPA1 from axolotls (Ambystoma mexicanum). We isolated a full-length cDNA of axolotl transient receptor potential ankyrin 1 (axTRPA1) and studied the functional properties by two-electrode voltage clamp method using Xenopus oocytes. Allyl isothiocyanate, caffeine, methyl anthranilate and carvacrol activated axTRPA1 channels. The results indicated that axTRPA1 is heat activated with the average threshold of 39.7°C, suggesting that axTRPA1 already has acquired the functional property of land animals.
Primary dysmenorrhea is a condition characterized by painful menstrual cramps that usually occurs in the absence of any identifiable pathological condition among menstruating women, with the prevalence estimates varying between 45% and 95%. Nonsteroidal anti-inflammatory drugs (NSAIDs) are considered as a standard treatment for primary dysmenorrhea; however, the failure rate of NSAIDs is often 20% to 25% and these drugs commonly cause adverse effects. In this review, we investigated the current evidence related to the effectiveness of Xuefu Zhuyu decoction (XZD) or Hyeolbuchukeo-tang, a traditional herbal formula, as a treatment for primary dysmenorrhea.
Patients with coronary heart disease (CHD) frequently have cardiovascular complications after undergoing PCI. Angiopoietin-2 (Ang-2) is an important proangiogenic factor that also plays an important role in atherosclerosis. This study aimed to evaluate the value of Ang-2 in predicting cardiovascular events after elective PCI.This prospective study enrolled 97 patients with CHD who underwent elective PCI from 2013 to 2014. Blood samples were collected in the first morning after admission and within 24 to 48 h after PCI. The primary endpoint was cardiovascular events, defined as a composite of cardiac death, nonfatal myocardial infarction/repeat revascularization, readmission for severe deterioration of angina and readmission for new onset heart failure. Based on the median level of pre-PCI or post-PCI Ang-2, the patients were divided into a low level group and a high level group.During the whole follow-up period (mean, 53 ± 13 months), Kaplan-Meier curves of cardiovascular events showed that there was no significant difference between the two pre-PCI groups (χ = 2.22, P = .137, and log-rank test) or the two post-PCI groups (χ = 2.83, P = .093, and log-rank test). However, in a multivariable Cox regression model, landmark analysis showed that the patients in high level group of post-PCI, not pre-PCI, were associated with remarkable higher risks of cardiovascular events compared to the low level group during the first 1.5 years of follow-up (adjusted HR = 9.99, 95%CI = 1.99-50.13, P = .005). However, that was of no significance from 1.5 years to maximum follow-up years (adjusted HR = 0.82, 95%CI = 0.26-2.59, P = .733).High Ang-2 levels of post-PCI can predict the occurrence of cardiovascular events in the short to medium term.
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