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Objective: To evaluate the extent to which cancer, a biological opposite to neurodegenerative disorders, may affect the onset and progression of Parkinson's disease (PD). Methods: A nested case-control design in consecutive PD patients with (cases) vs. without (controls) cancer was used to compare time to clinical diagnosis and time to Hoehn & Yahr (H&Y) staging score ≥ 3 as a measure of progression. Further, we compared PD onset and progression between cases with cancer diagnosis before (cancer before PD group) and after (cancer after PD group) PD onset. Independent variables were age at PD onset, motor subscale of the Movement Disorders Society-Unified Parkinson's Disease Rating Scale, sex, cognitive impairment, falls, depression, anxiety, dementia, and autonomic symptoms. Time to H&Y ≥ 3 was determined using Cox proportional hazards, with adjusted results summarized as hazards ratio (HR). Group differences were evaluated using unpaired t-test or Fisher's exact test. Results: The clinical PD onset was later in cases vs. controls (median 67.2 vs. 59.8 years; p < 0.001), but the adjusted time to H&Y ≥ 3 was similar between groups (HR = 0.67; p = 0.13). Skin cancers constituted 75% of all cancers in cases. Amongst skin cancers, compared to controls, cases had an older age at PD onset (67.8 vs. 59.8 years; p < 0.001). There was no difference in risk of progression in PD patients with skin cancer compared to controls (HR = 0.54, p = 0.09). Conclusions: Cancer, in particular of the skin, may delay the onset but not the progression of PD. Future prospective observational studies are warranted to elucidate the complex interactions between these biologically divergent disorders.
Background: Cervical dystonia is the most common form of focal dystonia. The frequency and pattern of degenerative changes of the cervical spine in patients with cervical dystonia and their relation to clinical symptoms remain unclear as no direct comparison to healthy controls has been performed yet. Here, we used magnetic resonance imaging (MRI) to investigate (1) whether structural abnormalities of the cervical spine are more common in patients with cervical dystonia compared to age-matched healthy controls, (2) if there are clinical predictors for abnormalities on MRI, and (3) to calculate the inter-rater reliability of the respective radiological scales. Methods: Twenty-five consecutive patients with cervical dystonia and 20 age-matched healthy controls were included in the study. MRI scans of the cervical spine were analyzed separately by three experienced raters blinded to clinical information, applying different MRI rating scales. Structural abnormalities were compared between groups for upper, middle, and lower cervical spine segments. The associations between scores differentiating both groups and clinical parameters were assessed in dystonia patients. Additionally, inter-rater reliability of the MRI scales was calculated. Results: Comparing structural abnormalities, we found minor differences in the middle cervical spine, indicated by a higher MRI total score in patients but no significant correlation between clinical parameters and MRI changes. Inter-rater reliability was satisfying for most of the MRI rating scales. Conclusion: Our results do not provide evidence for a role of MRI of the cervical spine in the routine work-up of patients with cervical dystonia in the absence of specific clinical signs or symptoms.
Filamentous fungi are important organisms in traditionally prepared amylase and alcohol-producing dry starters in India. We collected 40 diverse types of amylase and alcohol-producing starters from eight states in North East India viz. marcha, thiat, humao, hamei, chowan, phut, dawdim, and khekhrii. The average fungal population was 4.9 × 105 cfu/g with an average of pH 5.3 and 10.7%, respectively. In the present study, 131 fungal isolates were isolated and characterized based on macroscopic and microscopic characteristics and were grouped into 44 representative fungal strains. Based on results of morphological characteristics and ITS gene sequencing, 44 fungal strains were grouped into three phyla represented by Ascomycota (48%), Mucoromycota (38%), and Basidiomycota (14%). Taxonomical keys to species level was illustrated on the basis of morphological characteristics and ITS gene sequencing, aligned to the fungal database of NCBI GenBank, which showed seven genera with 16 species represented by Mucor circinelloides (20%), Aspergillus sydowii (11%), Penicillium chrysogenum (11%), Bjerkandera adusta (11%), Penicillium citrinum (7%), Rhizopus oryzae (7%), Aspergillus niger (5%), Aspergillus flavus (5%), Mucor indicus (5%) Rhizopus microsporus (5%), Rhizopus delemar (2%), Aspergillus versicolor (2%), Penicillium oxalicum (2%), Penicillium polonicum (2%), Trametes hirsuta (2%), and Cladosporium parahalotolerans (2%). The highest Shannon diversity index H was recorded in marcha of Sikkim (H: 1.74) and the lowest in hamei of Manipur (H: 0.69). Fungal species present in these amylolytic starters are morphologically, ecologically and phylogenetically diverse and showed high diversity within the community.
Microbial communities are continuously exposed to the arrival of alien species. In complex environments such as soil, the success of invasion depends on the characteristics of the habitat, especially the diversity and structure of the residing bacterial communities. While most data available on microbial invasion relies on experiments run under constant conditions, the fate of invading species when the habitat faces disturbances has not yet been addressed. Here, we designed experiments to assess the consequences of habitat disturbance on the success of ongoing microbial invasion. We investigated (i) if disturbance-induced alterations in resident microbial communities could mitigate or facilitate invasion of Listeria monocytogenes, (ii) if disturbance itself could either improve or reduce the invader's fitness and (iii) if the invading species alters the structure of indigenous microbial communities. Our data show that environmental disturbances affect invasion patterns of L. monocytogenes in soils. Intriguingly, successful invasion was recorded in a regimen of disturbances that triggered small changes in microbial community structure while maintaining high bacterial diversity. On the opposite, dramatic decline of the invader was recorded when disturbance resulted in emergence of specific communities albeit concomitant with a diversity loss. This suggests that community composition is more important than its diversity when it comes to prevent the establishment of an invading species. Finally, shifts in bacterial communities during the disturbance event were strengthened by the presence of the invader indicating a major impact of invasion on microbial diversity when the habitat faces disturbance.
Short-chain fatty acids (SCFA) are the main bacterial products of the catabolism of carbohydrates and proteins in the gut, and their role is essential in host-microbiota interactions. Acetic, propionic, and butyric acids are the major SCFA produced in the gut, and they have been extensively studied. In contrast, branched short-chain fatty acids (BCFA), mainly isovaleric and isobutyric acids, are produced in less amounts and their fecal levels in different human groups, intestinal microbial producing populations, and influence on health are insufficiently known. They have been proposed as markers of protein fermentation, which leads to the concomitant production of other fermentation products that can be harmful for the colon epithelium. In this context, the aim of this study was to shed light into the production of BCFA by the human intestinal microbiota, as related to age, body mass index (BMI), and diet. Fecal levels of the different SCFA were analyzed by gas chromatography in 232 healthy individuals with ages between 3 months and 95 years, and BMI in adults ranging from 19 to 54. Dietary assessments in adults were obtained through a food frequency questionnaire (FFQ). Molar proportions of BCFA in feces were strongly and positively related with aging. However, not a significant relationship was obtained between BCFA and BMI. A negative correlation was found between the consumption of dietary insoluble fiber and fecal levels of BCFA. More studies are needed for improving our understanding on the relationship of BCFA production profile with the intestinal microbiota composition and human health.
Aire is a transcriptional controller in medullary thymic epithelial cells (mTECs) modulating a set of peripheral tissue antigens (PTAs) and non-PTA mRNAs as well as miRNAs. Even miRNAs exerting posttranscriptional control of mRNAs in mTECs, the composition of miRNA-mRNA networks may differ. Under reduction in Aire expression, networks exhibited greater miRNA diversity controlling mRNAs. Variations in the number of 3'UTR binding sites of Aire-dependent mRNAs may represent a crucial factor that influence the miRNA interaction. To test this hypothesis, we analyzed through bioinformatics the length of 3'UTRs of a large set of Aire-dependent mRNAs. The data were obtained from existing RNA-seq of mTECs of wild type or Aire-knockout (KO) mice. We used computational algorithms as FASTQC, STAR and HTSEQ for sequence alignment and counting reads, DESEQ2 for the differential expression, 3USS for the alternative 3'UTRs and TAPAS for the alternative polyadenylation sites. We identified 152 differentially expressed mRNAs between these samples comprising those that encode PTAs as well as transcription regulators. In Aire KO mTECs, most of these mRNAs featured an increase in the length of their 3'UTRs originating additional miRNA binding sites and new miRNA controllers. Results from the in silico analysis were statistically significant and the predicted miRNA-mRNA interactions were thermodynamically stable. Even with no in vivo or in vitro experiments, they were adequate to show that lack of Aire in mTECs might favor the downregulation of PTA mRNAs and transcription regulators via miRNA control. This could unbalance the overall transcriptional activity in mTECs and thus the self-representation.
Innate immunity is the first line of defense against invading pathogens and may mediate HIV-1 resistance in HIV-1-exposed seronegative (HESN) individuals. This study aims to identify components of innate immunity that confer natural HIV-1 resistance in Chinese HESN individuals. Specifically, we compared the expression levels of Toll-like receptors (TLRs) and associated pathway molecules in peripheral blood mononuclear cells (PBMCs), monocytes/macrophages, and plasma obtained from HESN and control individuals. HESN individuals had higher expression of TLR9, IRF7, IFN-α/β, RANTES, and MIP-1α/1β in PBMCs and plasma than control subjects. Upon TLR9 stimulation, significantly higher expression of TLR9 and IRF7, as well as higher production of IFN-α/β, RANTES, and MIP-1α/1β, was observed in PBMCs and monocytes/macrophages from HESN individuals than in the corresponding cells from control individuals. More importantly, both with and without TLR9 stimulation, the levels of HIV-1 replication in monocyte-derived macrophages (MDMs) from HESN individuals were significantly lower than those in MDMs from control individuals. These data suggest that increased TLR9 activity and subsequent release of antiviral factors contribute to protection against HIV-1 in HESN individuals.
Alemtuzumab, a monoclonal antibody targeting CD52 that causes lymphocyte apoptosis, is a form of advanced immunosuppression that is currently used as a therapy for refractory acute cellular rejection and chronic lung allograft dysfunction in lung transplant recipients (1-3). Side effects of alemtuzumab include bone marrow suppression, infection, and malignancy. Whether alemtuzumab can be safely used in allograft recipients that have an increased propensity for bone marrow suppression due to telomeropathies is unknown. In a retrospective case series, we report outcomes associated with alemtuzumab in three lung allograft recipients with short telomere lengths, comparing endpoints such as leukopenia, transfusion needs, infection, hospitalization and survival to those of 17 patients without known telomeropathies that received alemtuzumab. We show that the use of alemtuzumab in lung transplant recipients with short telomeres is safe, though is associated with an increased incidence of neutropenia, thrombocytopenia and anemia requiring packed red blood cell transfusions. Alemtuzumab appears to be an acceptable advanced immunosuppressive therapy in patients with telomeropathies, though given the design and scope of this study, the actual clinical effect needs further evaluation in larger trials.
The mustard family (Brassicaceae) comprises several dozen monophyletic clades usually ranked as tribes. The tribe Boechereae plays a prominent role in plant research due to the incidence of apomixis and its close relationship to Arabidopsis. This tribe, largely confined to western North America, harbors nine genera and c. 130 species, with >90% of species belonging to the genus Boechera. Hundreds of apomictic diploid and triploid Boechera hybrids have spurred interest in this genus, but the remaining Boechereae genomes remain virtually unstudied. Here we report on comparative genome structure of six genera (Borodinia, Cusickiella, Phoenicaulis, Polyctenium, Nevada, and Sandbergia) and three Boechera species as revealed by comparative chromosome painting (CCP). All analyzed taxa shared the same seven-chromosome genome structure. Comparisons with the sister Halimolobeae tribe (n = 8) showed that the ancestral Boechereae genome (n = 7) was derived from an older n = 8 genome by descending dysploidy followed by the divergence of extant Boechereae taxa. As tribal divergence post-dated the origin of four tribe-specific chromosomes, it is proposed that these chromosomal rearrangements were a key evolutionary innovation underlaying the origin and diversification of the Boechereae in North America. Although most Boechereae genera exhibit genomic conservatism, intra-tribal cladogenesis has occasionally been accompanied by chromosomal rearrangements (particularly inversions). Recently, apomixis was reported in the Boechereae genera Borodinia and Phoenicaulis. Here, we report sexual reproduction in diploid Nevada, diploid Sandbergia, and tetraploid Cusickiella and aposporous apomixis in tetraploids of Polyctenium and Sandbergia. In sum, apomixis is now known to occur in five of the nine Boechereae genera.
Efforts to boost crop yield and meet global food demands while striving to reach sustainability goals are hindered by the increasingly severe impacts of abiotic stress, such as drought. One strategy for alleviating drought stress in crops is to utilize root-associated bacteria, yet knowledge concerning the relationship between plant hosts and their microbiomes during drought remain under-studied. One broad pattern that has recently been reported in a variety of monocot and dicot species from both native and agricultural environments, is the enrichment of Actinobacteria within the drought-stressed root microbiome. In order to better understand the causes of this phenomenon, we performed a series of experiments in millet plants to explore the roles of drought severity, drought localization, and root development in provoking Actinobacteria enrichment within the root endosphere. Through 16S rRNA amplicon-based sequencing, we demonstrate that the degree of drought is correlated with levels of Actinobacterial enrichment in four species of millet. Additionally, we demonstrate that the observed drought-induced enrichment of Actinobacteria occurs along the length of the root, but the response is localized to portions of the root experiencing drought. Finally, we demonstrate that Actinobacteria are depleted in the dead root tissue of Japanese millet, suggesting saprophytic activity is not the main cause of observed shifts in drought-treated root microbiome structure. Collectively, these results help narrow the list of potential causes of drought-induced Actinobacterial enrichment in plant roots by showing that enrichment is dependent upon localized drought responses but not root developmental stage or root death.
The biostimulant potential of three different organic acids (OAs) present in the rhizosphere, specifically lactic, oxalic, and citric acids, have been studied. The results showed a rapid and complete metabolism of these three acids with soil microorganisms using them as a source of carbon and energy. Biostimulation was confirmed by soil biochemical studies which showed an increase in enzymatic activities, such as dehydrogenase and phosphatase, lactic and citric acids being those that produced the greatest biostimulation. With regard to microbiota composition, amplicon sequencing of the 16S rRNA gene showed changes in the structure of soil microbial communities. Applying OAs produced a decrease in richness and diversity indices, inducing specific changes in the structure of the microbiological communities. Applying lactic acid induced rapid changes in microbiota composition at both phylum and family taxonomic levels, favoring the proliferation of microorganisms involved in its degradation and soil fertility, such as the genus Bacillus and the family Micrococcaceae. Once the lactic acid was degraded, the biodiversity tended to return to similar phyla, but specific distinctive families and genera remained, leaving a pattern of induction of taxa described as plant growth-promoting bacteria (PGPB), such as the Sinorhizobium and Lysobacter genera, and the Pseudomonaceae family. Similar behavior was found with citric acid, which favored the proliferation and dominance of microorganisms of the Clostridiaceae family, involved in its degradation, as well as microorganisms of both the Micrococcaceae and Pseudomonadaceae families which were found on day 7, leaving a similar pattern of induction as that found after the mineralization of lactic acid. On the other hand, oxalic acid induced long-lasting changes in the bacterial community composition. This was characterized by an increase in the proportion of the Burkholderiales order, which includes microorganisms involved in the degradation of this acid and microorganisms described as PGPB. This study presents evidence supporting the use of OAs as potential soil fertility inducers, due both to their effects in enhancing the dominance of taxa described as PGPB and to their stimulating soil microbial activity.
Insect herbivores have dramatic effects on the chemical composition of plants. Many of these induced metabolites contribute to the quality (e.g., flavor, human health benefits) of specialty crops such as the tea plant (Camellia sinensis). Induced chemical changes are often studied by comparing plants damaged and undamaged by herbivores. However, when herbivory is quantitative, the relationship between herbivore pressure and induction can be linearly or non-linearly density dependent or density independent, and induction may only occur after some threshold of herbivory. The shape of this relationship can vary among metabolites within plants. The tea green leafhopper (Empoasca onukii) can be a widespread pest on tea, but some tea farmers take advantage of leafhopper-induced metabolites in order to produce high-quality "bug-bitten" teas such as Eastern Beauty oolong. To understand the effects of increasing leafhopper density on tea metabolites important for quality, we conducted a manipulative experiment exposing tea plants to feeding by a range of E. onukii densities. After E. onukii feeding, we measured volatile and non-volatile metabolites, and quantified percent damaged leaf area from scanned leaf images. E. onukii density had a highly significant effect on volatile production, while the effect of leaf damage was only marginally significant. The volatiles most responsive to leafhopper density were mainly terpenes that increased in concentration monotonically with density, while the volatiles most responsive to leaf damage were primarily fatty acid derivatives and volatile phenylpropanoids/benzenoids. In contrast, damage (percent leaf area damaged), but not leafhopper density, significantly reduced total polyphenols, epigallocatechin gallate (EGCG), and theobromine concentrations in a dose-dependent manner. The shape of induced responses varied among metabolites with some changing linearly with herbivore pressure and some responding only after a threshold in herbivore pressure with a threshold around 0.6 insects/leaf being common. This study illustrates the importance of measuring a diversity of metabolites over a range of herbivory to fully understand the effects of herbivores on induced metabolites. Our study also shows that any increases in leafhopper density associated with climate warming, could have dramatic effects on secondary metabolites and tea quality.
Understanding combining ability and heterosis among diverse maize germplasm resources is important for breeding hybrid maize (Zea mays L.). Using 28 temperate and 23 tropical maize inbreds that represent different ecotypes and worldwide diversity of maize germplasm, we first developed a large-scale multiple-hybrid population (MHP) with 724 hybrids, which could be divided into three subsets, 325 temperate diallel hybrids and 136 tropical diallel hybrids generated in Griffing IV, and 263 temperate by tropical hybrids generated in NCD II. All the parental lines and hybrids were evaluated for 11 traits in replicated tests across two locations and three years. Several widely used inbreds showed strong general combining ability (GCA), and their derived hybrids showed strong specific combining ability (SCA). Heterosis is a quantifiable, trait-dependent and environment-specific phenotype, and the response of parental lines and their hybrids to environments resulted in various levels of heterosis. For all the tested traits except plant height and hundred grain weight (HGW), NCD II (temperate × tropical) hybrids showed higher average heterosis than the temperate and tropical diallel hybrids, with higher hybrid performance for ear length, ear diameter, and HGW. Tropical maize germplasm can be used to improve the yield potential for temperate lines. Grain number per row and grain number per ear were two most important traits that determined yield heterosis, which can be used as direct selection criteria for yield heterosis. The hybrids from heterotic groups, Reid × SPT, Reid × LRC, SPT × PA, and Lancaster × LRC, contributed highly significant positive SCA effects and strong heterosis to yield-related traits, and the heterotic patterns identified in this study were potentially useful for commercial maize breeding. Heterosis was more significantly and positively correlated with SCA than GCA, indicating that SCA can be used in heterosis prediction to develop potential hybrids in commercial maize breeding. The results of the present study not only contribute to developing breeding strategies, but also improve targeted breeding efficiency by using both temperate and tropical maize to broaden genetic basis. Large sets of parental lines with available genotypic information can be shared and used in worldwide hybrid breeding programs through an open-source breeding strategy. Potential applications of the reported results in developing hybrid maize breeding strategies were also discussed.
Plants experience low ambient temperature and low red to far-red ratios (L-R/FR) of light due to vegetative shading and longer twilight durations in cool seasons. Low temperature induce photoinhibition through inactivation of the photosynthetic apparatus, however, the role of light quality on photoprotection during cold stress remains poorly understood. Here, we report that L-R/FR significantly prevents the overreduction of the entire intersystem electron transfer chain and the limitation of photosystem I (PSI) acceptor side, eventually alleviating the cold-induced photoinhibition. During cold stress, L-R/FR activated cyclic electron flow (CEF), enhanced protonation of PSII subunit S (PsbS) and de-epoxidation state of the xanthophyll cycle, and promoted energy-dependent quenching (qE) component of non-photochemical quenching (NPQ), enzyme activity of Foyer-Halliwell-Asada cycle and D1 proteins accumulation. However, L-R/FR -induced photoprotection pathways were compromised in tomato PROTON GRADIENT REGULATION5 (PGR5) and PGR5-LIKE PHOTOSYNTHETIC PHENOTYPE1A (PGRL1A) co-silenced plants and NADH DEHYDROGENASE-LIKE COMPLEX M (NDHM) -silenced plants during cold stress. Our results demonstrate that both PGR5/PGRL1- and NDH-dependent CEF mediate L-R/FR -induced cold tolerance by enhancing the thermal dissipation and the repair of photodamaged PSII, thereby mitigating the overreduction of electron carriers and the accumulation of reactive oxygen species. The study indicates that there is an anterograde link between photoreception and photoprotection in tomato plants during cold stress.
Pathogen infection triggers extensive reprogramming of the plant transcriptome, including numerous genes the function of which is unknown. Due to their wide taxonomic distribution, genes encoding proteins with Domains of Unknown Function (DUFs) activated upon pathogen challenge likely play important roles in disease. In Arabidopsis thaliana, we identified thirteen genes harboring a DUF4228 domain in the top 10% most induced genes after infection by the fungal pathogen Sclerotinia sclerotiorum. Based on functional information collected through homology and contextual searches, we propose to refer to this domain as the pathogen and abiotic stress response, cadmium tolerance, disordered region-containing (PADRE) domain. Genome-wide and phylogenetic analyses indicated that PADRE is specific to plants and diversified into 10 subfamilies early in the evolution of Angiosperms. PADRE typically occurs in small single-domain proteins with a bipartite architecture. PADRE N-terminus harbors conserved sequence motifs, while its C-terminus includes an intrinsically disordered region with multiple phosphorylation sites. A pangenomic survey of PADRE genes expression upon S. sclerotiorum inoculation in Arabidopsis, castor bean, and tomato indicated consistent expression across species within phylogenetic groups. Multi-stress expression profiling and co-expression network analyses associated AtPADRE genes with the induction of anthocyanin biosynthesis and responses to chitin and to hypoxia. Our analyses reveal patterns of sequence and expression diversification consistent with the evolution of a role in disease resistance for an uncharacterized family of plant genes. These findings highlight PADRE genes as prime candidates for the functional dissection of mechanisms underlying plant disease resistance to fungi.
Cancer cachexia is a metabolic syndrome with alterations in gene regulatory networks that consequently lead to skeletal muscle wasting. Integrating microRNAs-mRNAs omics profiles offers an opportunity to understand transcriptional and post-transcriptional regulatory networks underlying muscle wasting. Here, we used RNA sequencing to simultaneously integrate and explore microRNAs and mRNAs expression profiles in the tibialis anterior (TA) muscles of the Lewis Lung Carcinoma (LLC) model of cancer cachexia. We found 1,008 mRNAs and 18 microRNAs differentially expressed in cachectic mice compared with controls. Although our transcriptomic analysis demonstrated a high heterogeneity in mRNA profiles of cachectic mice, we identified a reduced number of differentially expressed genes that were uniformly regulated within cachectic muscles. This set of uniformly regulated genes is associated with the extracellular matrix (ECM), proteolysis, and inflammatory response. We also used transcriptomic data to perform enrichment analysis of transcriptional factor binding sites in promoter sequences, which revealed activation of the atrophy-related transcription factors NF-κB, Stat3, AP-1, and FoxO. Furthermore, the integration of mRNA and microRNA expression profiles identified post-transcriptional regulation by microRNAs of genes involved in ECM organization, cell migration, transcription factors binding, ion transport, and the FoxO signaling pathway. Our integrative analysis of microRNA-mRNA co-profiles comprehensively characterized regulatory relationships of molecular pathways and revealed microRNAs targeting ECM-associated genes in cancer cachexia.
Increasing evidence has revealed close relationships between long non-coding RNAs (lncRNAs) and chemoresistance in multiple types of tumors; however, functional lncRNAs in breast cancer (BC) have not been completely identified. In this study, we aimed to identify novel lncRNAs that might play critical roles in doxorubicn resistance, which could reveal potential biomarkers of BC. Using a BC dataset (GSE81971), we identified 452 lncRNAs that were upregulated and 659 that were downregulated; furthermore, there were 1896 differentially expressed mRNAs, of which 1137 were upregulated and 758 were downregulated in MCF-7/ADR cells compared with the expression in MCF-7 cells. We constructed an lncRNA-mRNA network by integrating probe reannotation and regulatory interactions. To elucidate the key lncRNAs in BC, we further analyzed dysregulated lncRNA-mRNA crosstalk, and six candidate lncRNAs (lnc-TRDMT1-5, ZNF667-AS1, lnc-MPPE1-13, DSCAM-AS1:5, DSCAM-AS1:2, and lnc-CFI-3) were identified. Notably, the expression level of lnc-TRDMT1-5 was significantly upregulated in resistant cells compared with sensitive cells, and its levels were increased in BC tissues compared with adjacent tissues. Levels were positively associated with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) expression levels. High expression of lnc-TRDMT1-5 predicted poor prognosis in ER-positve and HER2-positive BC patients, especially in patients with chemoresistance. Bioinformatic and functional analysis revealed that lnc-TRDMT1-5 was involved in many crucial pathways in cancer, such as the PI3K/AKT and Wnt signaling pathways. Subcellular localization predicted that lnc-TRDMT1-5 was located in the cytoplasm, and the lncRNA-miRNA-mRNA network showed that lnc-TRDMT1-5 might serve as a regulator in BC. Here, our results demonstrated a dysregulated lncRNA-mRNA network that might provide new treatment strategies for chemoresistant BC, and the results identified a new lncRNA, lnc-TRDMT1-5, with oncogenic and prognostic functions in human BC.
Frailty is a multidimensional syndrome that reflects the physiological reserve of elderly. It is related to unfavorable outcomes in various cardiovascular conditions. We conducted a systematic review and meta-analysis of the association of frailty with all-cause mortality and bleeding after acute myocardial infarction (AMI) in the elderly.
Midgut volvulus in pregnancy is rare but life-threatening, resulting in high maternal and fetal mortality. This surgical emergency commonly masquerades as symptoms of pregnancy, which together with its low incidence often leads to delay in diagnosis and definitive treatment. Here, we review the last three decades of the literature, discuss the challenges in managing this rare condition, and raise awareness among clinicians to minimise loss of life.
Even though a great improvement in the last twenty years, the problem of newborn deaths is still remaining. In 2017 alone, an estimated 2.5 million neonatal deaths occurred worldwide, around 39 percent of all deaths in sub-Saharan Africa. Early detection of neonatal illness is an important step towards improving newborn survival. If mothers know the appropriate manifestations of the causes of death in newborns (neonatal danger signs), it is possible to avert related mortality, because of the health-seeking behavior of mothers highly relies on their knowledge of neonatal danger signs.
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