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A two-hub-protein-based risk score system might be used for predicting tumor recurrence in rectal MAC patients. SIGNIFICANCE NCRT resistance is a major problem in the treatment of rectal MAC patients. Identifying robust predictive biomarkers for NCRT resistance is beneficial to the stratified treatment of rectal MAC patients. In this study, label-free mass spectrometry and weighted gene co-expression network analysis identified ENOA as a potential novel biomarker for the NCRT response and prognosis. ENOA may be involved in the process of the NCRT resistance and tumor recurrence through the carbon metabolism pathway.Over the last 20 years, advances in sequencing technologies paired with biochemical and structural studies have shed light on the unique pharmacological arsenal produced by the salivary glands of hematophagous arthropods that can target host hemostasis and immune response, favoring blood acquisition and, in several cases, enhancing pathogen transmission. Here we provide a deeper insight into Xenopsylla cheopis salivary gland contents pairing transcriptomic and proteomic approaches. Sequencing of 99 pairs of salivary glands from adult female X. cheopis yielded a total of 7432 coding sequences functionally classified into 25 classes, of which the secreted protein class was the largest. The translated transcripts also served as a reference database for the proteomic study, which identified peptides from 610 different proteins. Both approaches revealed that the acid phosphatase family is the most abundant salivary protein group from X. cheopis. Additionally, we report here novel sequences similar to the FS-H famicing methods paired with LC-MS/MS analysis, revealing its unique composition compared to the sialomes of other blood-feeding arthropods, and highlighting the different pathways taken during the evolution of salivary gland concoctions. In the absence of the X. cheopis genome sequence, this work serves as an extended reference for the identification of potential pharmacological proteins and peptides present in flea saliva.Syndecans belong to the family of transmembrane heparan sulfate proteoglycans and are associated with many physiopathological processes, including oral cancer. As previously shown soluble syndecan-1 (SDC1) fragments and synthetic SDC1 peptide were able to induce cell migration in oral cancer cell lines. In order to explore the role of SDC1 in oral cancer, we have investigated SDC1 interacting partners and its functional role in oral cancer models. Here we have shown that SDC1 interacts with follistatin-related protein 1 (FSTL1) by its ectodomain (ectoSDC1) and extracellular juxtamembrane peptide (pepSDC1) and that their transcript levels can affect tumor events. Using orthotopic mouse model we identified that the knock-down for FSTL1 (shFSTL1) or for both FSTL1 and SDC1 (sh2KD) produced less aggressive and infiltrative tumors, with lower keratinization deposition, but with increased levels of epithelial-mesenchymal transition and proliferation compared to control and SDC1 knock-down. Based on cell culture assays, we suggest that the shFSTL1 effect on tumor tissues might be from significant increase of mRNA levels of Activin A (ActA) and its resceptors. This study shows for the first time two different complexes, SDC1 and FSTL1; pepSDC1 and FSTL1, exhibiting a close relationship in cell signaling events, as FSTL1 promotes a more aggressive phenotype. SIGNIFICANCE This work contributes to the understanding of new SDC1 functions, based on the investigation of protein-protein complex formation in Oral Squamous cell carcinoma (OSCC) models. The FSTL1 identification, as an interacting partner of SDC1 ectodomain and of its derived peptide promotes molecular events that favors cancer development and progression, as highlighted by Activin A (ActA) and Epithelial-mesenchymal transition (EMT) gene expression and by changes in the phenotype of orthotopic OSCC mouse tumor tissues when SDC1-FSTL1 expression is modulated.Co-immunoprecipitation of proteins coupled to mass spectrometry is critical for the understanding of protein interaction networks. In instances where a suitable antibody is not available, it is common to graft synthetic tags onto a target protein sequence thereby allowing the use of commercially available antibodies for affinity purification. A common approach is through FLAG-Tag co-immunoprecipitation. To allow the selective elution of protein complexes, competitive displacement using a large molar excess of the tag peptides is often carried out. Yet, this creates downstream challenges for the mass spectrometry analysis due to the presence of large quantities of these peptides. Here, we demonstrate that Field Asymmetric Ion Mobility Spectrometry (FAIMS), a gas phase ion separation device prior to mass spectrometry analysis can be applied to FLAG-Tag co-immunoprecipitation experiments to increase the depth of protein coverage. By excluding these abundant tag peptides, we were able to observe deeper coverage of interacting proteins and as a result, deeper biological insights, without the need for additional sample handling or altering sample preparation protocols. SIGNIFICANCE We have shown that application of FAIMS separation in the gas phase can increase the proteome coverage of Flag-Tagged co-immunoprecipitation mass spectrometry experiments versus one without FAIMS. We were able to observe deeper coverage of interacting proteins and as a result, deeper biological insights, without additional sample handling, fractionation, machine run time or modifying the sample preparation protocol.Statin-associated muscle symptoms (SAMS) are the main side effects of statins. Currently, there are no effective biomarkers for accurate clinical diagnosis. Urine is not subject to homeostatic control and therefore accumulates early changes, making it an ideal biomarker source. We therefore examined urine proteome changes associated with SAMS. Here, we established a SAMS rat model by intragastric intubation with simvastatin (80 mg/kg). Biochemical analyses and hematoxylin and eosin staining were used to evaluate the degree of muscle injury. The urine proteome on days 3, 6, 9 and 14 was profiled using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Differential proteins on day 14 of SAMS were mainly associated with glycolysis/gluconeogenesis, pyruvate metabolism, metabolism of reactive oxygen species and apoptosis, which were associated with the pathological mechanism of SAMS. Among the 14 differential proteins on day 3, Fibrinogen gamma chain (FIBG), Osteopontin (OSTP) and C-reactive protein (CRP) were associated with muscle damage, while EH domain-containing protein 1(EHD1), Cubilin (CUBN) and Fibronectin (FINC) were associated with the pathogenic mechanisms of SAMS. Our preliminary results indicated that the urine proteome can reflect early changes in the SAMS rat model, providing the potential for monitoring drug side effects in future clinical research. SIGNIFICANCE This study demonstrate that the early muscle damage caused by simvastatin can be reflected in urinary proteins. The urine proteome also has the potential to reflect the pharmacology and toxicology of drugs in future clinical research.We retrospectively analyzed seven patients with Actinotignum schaalii bacteremia in a tertiary hospital in Japan. Pyelonephritis was the most frequent source of bacteremia, followed by Fournier's gangrene and pyometra. All patients with pyelonephritis had underlying urological conditions, ureteral stents, nephrostomy, ureteral stones, or ureterocele.Anaerobic cocci are common anaerobic isolates. Numerous genera of anaerobic cocci have been reported in both urinary tract microbiota, mainly of females, and in cases of urinary tract infections (UTIs), predominantly in patients with comorbidities, when no facultatively anaerobic bacteria were detected from the urine samples. UTIs caused by anaerobic cocci have been reported in >7% in some studies. As the routine diagnostic methods may be insufficient to detect and identify the anaerobic cocci in patients with UTIs, enhanced quantitative urine culture (EQUC) can give better results. EQUC is performed by plating urine samples onto different media to be incubated in both aerobic and anaerobic conditions with a prolonged incubation time. Other newer methods such as 16S rRNA gene sequencing, qualitative PCR and Next Generation Sequencing can also be considered. Anaerobic cocci such as Peptoniphilus, Parvimonas, Anaerococcus and Finegoldia spp. were found in patients with bacteremia of urinary source. A fatal outcome has been reported in a diabetic patient with emphysematous pyelonephritis caused by Finegoldia magna and Candida parapsilosis due to a delay in seeking hospital care during the COVID-19 pandemic. In specific cases such as of chronic infections, immunosuppression, comorbidity, advanced age, following urological tract manipulations and negative culture results for usual uropathogens, it may be advisable to use suprapubic aspiration cultured in both aerobic and anaerobic condition or EQUC using media which support the relative slow growing anaerobic cocci as well.Clostridioides difficile has been identified as one of the primary etiologic agents of nosocomial diarrhea and pseudomembranous colitis in humans and other mammals associated following broad-spectrum antibiotics use. In Rio de Janeiro, Brazil we describe a case of C. difficile infection (CDI) in a 13-year-old male dog.The opportunistic intestinal pathogen Clostridioides difficile is the number one cause of nosocomial diarrhea in humans. In this study, C. difficile was isolated from 26.7% of potatoes and 1.9% of salads from German retail. The majority of strains possessed toxinogenic PCR-ribotypes that are associated with human clinical cases pointing towards a potential risk to human health.We reviewed the molecular epidemiology of Clostridioides difficile infection (CDI) in Japan by reviewing articles in which typing analysis was performed on recovered C. difficile isolates. Most of the multicenter studies showed that the major prevalent PCR-ribotypes (RT018-related type, RT014, RT002, RT369, and RT017) accounted for more than 75% of clinical isolates in Japan, which has not changed significantly since the late 1990s. Within the RT018-related isolates, a shift from RT018 to RT018'' (QX239) and the persistence of high levels of antimicrobial resistance were observed. Among toxin A-negative, toxin B-positive C. difficile, RT017 was replaced by RT369, which was more resistant to fluoroquinolone. The isolation rate of binary toxin-positive isolates was low (2-6%), except in one study (10%). Isolation of RT027 and RT078 was rare in endemic settings, while there was a first report of a nosocomial outbreak due to RT027 C. difficile in 2019. Notably, the vast majority of RT027 isolates, including the epidemic strain responsible for the outbreak, were susceptible to moxifloxacin, suggesting that Japanese RT027 represents the pre-epidemic RT027 genetic background. To understand the CDI burden in Japan, a nationwide strain-based surveillance system is imperative.Tumor local chemotherapy employing injectable hydrogel reservoirs is a promising platform to achieve precise drug administration. However, balanced injectability, pH-responsiveness and long-term hydrolysis resistance of self-healing hydrogels remain appealing challenges. Herein, a modular preassembly strategy combining host-guest interactions with dynamic acylhydrazone bonds, was exploited to fabricate injectable cellulose-based hydrogels (CAAs) dressed with self-healing properties, pH-responsiveness and hydrolytic degradation resistance. Attributed to the host-guest interaction between β-cyclodextrin (CD) and 1-adamantane (AD), the hydrogels exhibited injectability, self-healing properties (healing efficiency of 97.5%) and rapid recovery ( 30 days) and pH-responsive behavior, endowing the hydrogels with precise spatiotemporal drug release administration. G007-LK The in vivo application of CAA as a carrier was studied using doxorubicin (DOX) model drug, and the results shows that using CAA as DOX carrier not only greatly enhances the anti-tumor efficacy of DOX, but also reduced the side effects of DOX.
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