On account of its proven clinical efficacy, the combination of systemically administered amoxicillin and metronidazole is frequently adjuncted to non-operative periodontal therapy and well documented. Potential drawbacks of this regimen, e.g., side effects and problems with the compliance, led to an ongoing search for alternatives. Azithromycin, an antibiotic extensively used in general medicine, has recently found its niche in periodontal therapy as well. This systematic review aimed to analyze the in vitro antimicrobial efficacy of amoxicillin plus metronidazole versus azithromycin. For this purpose, a systematic literature search was performed, and studies published up to 29 March 2018 referenced in Medline, Embase, Cochrane, and Biosis were independently screened by two authors. An additional hand search was performed and studies focusing on the evaluation of in vitro antimicrobial efficacy of amoxicillin + metronidazole or azithromycin on bacteria from the subgingival biofilm were included. English and German language research reports were considered. From 71 identified articles, only three articles were eligible for inclusion. These studies showed heterogeneity in terms of analytical methods and strains explored. However, all studies used multispecies biofilm models for analysis of the antimicrobial activity. Unanimously, studies reported on more pronounced antimicrobial effects when applying the combination of amoxicillin + metronidazole, compared to azithromycin. Based on the few studies available, the combination of amoxicillin + metronidazole seemed to display higher antimicrobial efficacy in vitro than azithromycin.

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

Tomato plants are attacked by diverse herbivorous arthropods, including by cell-content-feeding mites, such as the extreme generalist Tetranychus urticae and specialists like Tetranychus evansi and Aculops lycopersici. Mite feeding induces plant defense responses that reduce mite performance. However, T. evansi and A. lycopersici suppress plant defenses via poorly understood mechanisms and, consequently, maintain a high performance on tomato. On a shared host, T. urticae can be facilitated by either of the specialist mites, likely due to the suppression of plant defenses. To better understand defense suppression and indirect plant-mediated interactions between herbivorous mites, we used gene-expression microarrays to analyze the transcriptomic changes in tomato after attack by either a single mite species (T. urticae, T. evansi, A. lycopersici) or two species simultaneously (T. urticae plus T. evansi or T. urticae plus A. lycopersici). Additionally, we assessed mite-induced changes in defense-associated phytohormones using LC-MS/MS. Compared to non-infested controls, jasmonates (JAs) and salicylate (SA) accumulated to higher amounts upon all mite-infestation treatments, but the response was attenuated after single infestations with defense-suppressors. Strikingly, whereas 8 to 10% of tomato genes were differentially expressed upon single infestations with T. urticae or A. lycopersici, respectively, only 0.1% was altered in T. evansi-infested plants. Transcriptome analysis of dual-infested leaves revealed that A. lycopersici primarily suppressed T. urticae-induced JA defenses, while T. evansi dampened T. urticae-triggered host responses on a transcriptome-wide scale. The latter suggests that T. evansi not solely down-regulates plant gene expression, but rather directs it back towards housekeeping levels. Our results provide valuable new insights into the mechanisms underlying host defense suppression and the plant-mediated facilitation of competing herbivores.

MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown.

Pooling techniques, where multiple sub-samples are mixed in a single sample, are widely used to take full advantage of high-throughput DNA sequencing. Recently, Ranjard et al. (PLoS ONE 13:0195090, 2018) proposed a pooling strategy without the use of barcodes. Three sub-samples were mixed in different known proportions (i.e. 62.5%, 25% and 12.5%), and a method was developed to use these proportions to reconstruct the three haplotypes effectively.

Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype.

Resolving the historical biogeography of the leopard (Panthera pardus) is a complex issue, because patterns inferred from fossils and from molecular data lack congruence. Fossil evidence supports an African origin, and suggests that leopards were already present in Eurasia during the Early Pleistocene. Analysis of DNA sequences however, suggests a more recent, Middle Pleistocene shared ancestry of Asian and African leopards. These contrasting patterns led researchers to propose a two-stage hypothesis of leopard dispersal out of Africa: an initial Early Pleistocene colonisation of Asia and a subsequent replacement by a second colonisation wave during the Middle Pleistocene. The status of Late Pleistocene European leopards within this scenario is unclear: were these populations remnants of the first dispersal, or do the last surviving European leopards share more recent ancestry with their African counterparts?

Nitrilases are nitrile-converting enzymes commonly found within the plant kingdom that play diverse roles in nitrile detoxification, nitrogen recycling, and phytohormone biosynthesis. Although nitrilases are present in all higher plants, little is known about their function in trees. Upon herbivory, poplars produce considerable amounts of toxic nitriles such as benzyl cyanide, 2-methylbutyronitrile, and 3-methylbutyronitrile. In addition, as byproduct of the ethylene biosynthetic pathway upregulated in many plant species after herbivory, toxic β-cyanoalanine may accumulate in damaged poplar leaves. In this work, we studied the nitrilase gene family in Populus trichocarpa and investigated the potential role of the nitrilase PtNIT1 in the catabolism of herbivore-induced nitriles.

Nanoparticle albumin-bound (nab)-paclitaxel has better efficacy, safety profiles, and no need to use prophylactic steroids compared with solvent-based paclitaxel. We performed a single arm, phase II study to evaluate the efficacy and safety of weekly nab-paclitaxel and gemcitabine combination in patients with metastatic breast cancer (MBC) and explored role of tumor/stromal Caveolin-1 (Cav-1) as a predictive biomarker for the efficacy.

Maternal lifestyle factors, including smoking and increased body weight, increase risks of adult diseases such as metabolic syndrome and infertility. The fetal thyroid gland is essential for the control of fetal metabolic rate, cardiac output, and brain development. Altered fetal thyroid function may contribute to increased disease onset later in life. Here, we investigated the impact of maternal smoking and high maternal weight on human fetal thyroid function during the second trimester.

The use of herbal medicines in developing countries has been increasing over the years. In Ghana, since 2011, the government has been piloting the integration of herbal medicine in 17 public hospitals. However, the strengths and the weaknesses of the integration have not been fully explored. The current study sought to examine the strengths and weaknesses of the integration using the WHO health systems framework.

A proprietary composition GMCT contains extracts of two popular Asian herbs viz., Garcinia mangostana (GM) fruit rind and Cinnamomum tamala (CT) leaf. We systematically evaluated physical performance and muscle strength enhancing ability of GMCT in a preclinical mouse model followed by a 42-days double-blind placebo controlled human trial in resistance trained adult males.

Acute kidney injury (AKI) is an important health issue concerning ∼50% of patients treated in intensive care units. AKI mainly occurs after sepsis, acute ischemia, nephrotoxicity, or hypoxia and leads to severe damage of the kidney and to an increased risk of mortality. The diagnosis of AKI is currently based on creatinine urea levels and diuresis. Yet, novel markers may improve the accuracy of this diagnosis at an early stage of the disease, thereby allowing early prevention and therapy, ultimately leading to a reduction in the need for renal replacement therapy and decreased mortality. Non-protein-coding RNAs or noncoding RNAs are central players in development and disease. They are important regulatory molecules that allow a fine-tuning of gene expression and protein synthesis. This regulation is necessary to maintain homeostasis, and its dysregulation is often associated with disease development. Noncoding RNAs are present in the kidney and in body fluids and their expression is modulated during AKI. This review article assembles the current knowledge of the role of noncoding RNAs, including microRNAs, long noncoding RNAs and circular RNAs, in the pathogenesis of AKI. Their potential as biomarkers and therapeutic targets as well as the challenges to translate research findings to clinical application are discussed. Although microRNAs have entered clinical testing, preclinical and clinical trials are needed before long noncoding RNAs and circular RNAs may be considered as useful biomarkers or therapeutic targets of AKI.

Intestinal release of dietary triglycerides via chylomicrons is the major contributor to elevated postprandial triglyceride levels. Dietary lipids can be transiently stored in cytosolic lipid droplets (LDs) located in intestinal enterocytes for later release. ADP ribosylation factor-related protein 1 (ARFRP1) participates in processes of LD growth in adipocytes and in lipidation of lipoproteins in liver and intestine. This study aims to explore the impact of ARFRP1 on LD organization and its interplay with chylomicron-mediated triglyceride release in intestinal-like Caco-2 cells. Suppression of Arfrp1 reduced release of intracellularly derived triglycerides (0.69-fold) and increased the abundance of transitional endoplasmic reticulum ATPase TERA/VCP, fatty acid synthase-associated factor 2 (FAF2) and perilipin 2 (Plin2) at the LD surface. Furthermore, TERA/VCP and FAF2 co-occurred more frequently with ATGL at LDs, suggesting a reduced adipocyte triglyceride lipase (ATGL)-mediated lipolysis. Accordingly, inhibition of lipolysis reduced lipid release from intracellular storage pools by the same magnitude as Arfrp1 depletion. Thus, the lack of Arfrp1 increases the abundance of lipolysis-modulating enzymes TERA/VCP, FAF2 and Plin2 at LDs, which might decrease lipolysis and reduce availability of fatty acids for triglyceride synthesis and their release via chylomicrons.

Researchers have shown that long noncoding RNAs (lncRNAs) are closely associated with the pathogenesis of colorectal cancer (CRC). In here, we aimed to explore the function of lncRNA MAFG-AS1 in tumorigenesis of CRC. Firstly, we found that the expression of MAFG-AS1 was upregulated in CRC tissues and positively correlated with the advanced tumor stage. A reciprocal repression was found between MAFG-AS1 and miR-147b. The expression of miR-147b was downregulated in CRC tissues and inversely correlated with MAFG-AS1. Both the low-expression of miR-147b expression and the advanced tumor stage were independent factor for poor survival probability. Furthermore, overexpression of MAFG-AS1 promoted cell proliferation, cell cycle progression, and invasion, and inhibited apoptosis, while transduction of miR-147b partially reversed the effect of MAFG-AS1 on cellular processes. Consistently, stable over-expression of MAFG-AS1 contributed to the growth of colon cancer cell xenografts in vivo. NDUFA4 was identified as a direct target of miR-147b and knockdown of NDUFA4 abolished the oncogenic role of miR-147b inhibitor. Besides, MAFG-AS1 contributed to cell glycolysis by sponging miR-147b and activation of NDUFA4, causing an upregulation of PDK1, PFK1 and PKM2. Taken together, our study suggested that MAFG-AS1 functions as a novel oncogenic lncRNA in the development of CRC by regulating miR-147b/NDUFA4.

The mechanism behind an increased risk of recurrent pregnancy loss (RPL) remains largely unknown. In our previous study, we identified that inter-α-trypsin inhibitor heavy chain 4 (ITI-H4) is highly expressed at a modified molecular weight of 36 kDa in serum derived from RPL patients. Yet, the precise molecular mechanism and pathways by which the short form of ITI-H4 carries out its function remain obscure.

Pain is a common condition with a significant physical, psychosocial, and economic impact. Due to enormous progress in mobile device technology as well as the increase in smartphone ownership in the general population, mobile apps can be used to monitor patients with pain and support them in pain management.

The correct assembly of ribosomes from ribosomal RNAs (rRNAs) and ribosomal proteins (RPs) is critical, as indicated by the diseases caused by RP haploinsufficiency and loss of RP stoichiometry in cancer cells. Nevertheless, how assembly of each RP is ensured remains poorly understood. We use yeast genetics, biochemistry, and structure probing to show that the assembly factor Ltv1 facilitates the incorporation of Rps3, Rps10, and Asc1/RACK1 into the small ribosomal subunit head. Ribosomes from Ltv1-deficient yeast have substoichiometric amounts of Rps10 and Asc1 and show defects in translational fidelity and ribosome-mediated RNA quality control. These defects provide a growth advantage under some conditions but sensitize the cells to oxidative stress. Intriguingly, relative to glioma cell lines, breast cancer cells have reduced levels of LTV1 and produce ribosomes lacking RPS3, RPS10, and RACK1. These data describe a mechanism to ensure RP assembly and demonstrate how cancer cells circumvent this mechanism to generate diverse ribosome populations that can promote survival under stress.

Cas9 nuclease is the key effector of type II CRISPR adaptive immune systems found in bacteria. The nuclease can be programmed by a single guide RNA (sgRNA) to cleave DNA in a sequence-specific manner. This property has led to its widespread adoption as a genome editing tool in research laboratories and holds great promise for biotechnological and therapeutic applications. The general mechanistic features of catalysis by Cas9 homologs are comparable; however, a high degree of diversity exists among the protein sequences, which may result in subtle mechanistic differences. S. aureus (SauCas9) and especially S. pyogenes (SpyCas9) are among the best-characterized Cas9 proteins and share ∼17% sequence identity. A notable feature of SpyCas9 is an extremely slow rate of reaction turnover, which is thought to limit the amount of substrate DNA cleavage. Using in vitro biochemistry and enzyme kinetics, we directly compare SpyCas9 and SauCas9 activities. Here, we report that in contrast to SpyCas9, SauCas9 is a multiple-turnover enzyme, which to our knowledge is the first report of such activity in a Cas9 homolog. We also show that DNA cleaved with SauCas9 does not undergo any detectable single-stranded degradation after the initial double-stranded break observed previously with SpyCas9, thus providing new insights and considerations for future design of CRISPR/Cas9-based applications.

Dephosphorylation of the inhibitory "S259" site on RAF kinases (S259 on CRAF, S365 on BRAF) plays a key role in RAF activation. The MRAS GTPase, a close relative of RAS oncoproteins, interacts with SHOC2 and protein phosphatase 1 (PP1) to form a heterotrimeric holoenzyme that dephosphorylates this S259 RAF site. MRAS and SHOC2 function as PP1 regulatory subunits providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells. SHOC2's predicted structure shows remarkable similarities to the A subunit of PP2A, suggesting a case of convergent structural evolution with the PP2A heterotrimer. We have identified multiple regions in SHOC2 involved in complex formation as well as residues in MRAS switch I and the interswitch region that help account for MRAS's unique effector specificity for SHOC2-PP1. MRAS, SHOC2, and PPP1CB are mutated in Noonan syndrome, and we show that syndromic mutations invariably promote complex formation with each other, but not necessarily with other interactors. Thus, Noonan syndrome in individuals with SHOC2, MRAS, or PPPC1B mutations is likely driven at the biochemical level by enhanced ternary complex formation and highlights the crucial role of this phosphatase holoenzyme in RAF S259 dephosphorylation, ERK pathway dynamics, and normal human development.