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Helicobacter pylori (H. pylori) is a causative agent of various gastrointestinal diseases and eradication mainly relies on antibiotic treatment, with (AMX) being a key component. However, rising antibiotic resistance in H. pylori necessitates the use of antibiotics combination therapy, often disrupting gut microbiota equilibrium leading to further health complications. This study investigates a novel strategy utilizing AMX-loaded chitosan nanoparticles (AMX-CS NPs), co-administered with prebiotic inulin to counteract H. pylori infection while preserving microbiota health. Following microbroth dilution method, AMX displayed efficacy against H. pylori, with a MIC 50 of 48.34 ± 3.3 ng/mL, albeit with a detrimental impact on Lactobacillus casei (L. casei). The co-administration of inulin (500 μg/mL) with AMX restored L. casei viability while retaining the lethal effect on H. pylori. Encapsulation of AMX in CS-NPs via ionic gelation method, resulted in particles of 157.8 ± 3.85 nm in size and an entrapment efficiency (EE) of 86.44 ± 2.19 %. Moreover, AMX-CS NPs showed a sustained drug release pattern over 72 h with no detectable toxicity on human dermal fibroblasts cell lines. Encapsulation of AMX into CS NPs also reduced its MIC 50 against H. pylori, while its co-administration with inulin maintained L. casei viability. Interestingly, treatment with AMX-CS NPs also reduced the expression of the efflux pump gene hefA in H. pylori. This dual treatment strategy offers a promising approach for more selective antimicrobial treatment, minimizing disruption to healthy microbial communities while effectively addressing pathogenic threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Functionalized metal oxide nanoparticles (NPs) have demonstrated specific binding affinity to antigens or receptors presented on the cancer cell surface, favouring selective targeting and minimizing side effects during the chemotherapy. Placenta-specific protein 1 (PLAC-1) is a small cell surface protein overexpressed in certain types of breast cancer (BC); therefore, it can be used as a therapeutic target. The objective of this study is to develop NPs that can bind PLAC-1 and hence can inhibit the progression and metastatic potential of BC cells. Zinc oxide (ZnO) NPs were coated with a peptide (GILGFVFTL), which possesses a strong binding ability to PLAC-1. The physical attachment of the peptide to ZnO NPs was verified through various physicochemical and morphological characterization techniques. The selective cytotoxicity of the designed NPs was investigated using PLAC-1-bearing MDA-MB 231 human BC cell line and compared to LS-180 cells that do not express PLAC-1. The anti-metastatic and pro-apoptotic effects of the functionalized NPs on MDA-MB 231 cells were examined. Confocal microscopy was used to investigate the mechanism of NPs uptake by MDA-MB 231 cells. Compared to non-functionalized NPs, peptide functionalization significantly improved the targeting and uptake of the designed NPs by PLAC-1-expressing cancer cells with significant pro-apoptotic and anti-metastatic effects. The uptake of peptide functionalized ZnO NPs (ZnO-P NPs) occurred via peptide-PLAC1 interaction-assisted clathrin-mediated endocytosis. These findings highlight the potential targeted therapy of ZnO-P NPs against PLAC-1-expressing breast cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We investigated whether a 6-amino acid insertion/deletion polymorphism in the mucin domain of TIM-1 (T-cell immunoglobulin and mucin domain 1), modulates susceptibility to HIV-1 infection. The polymorphism was genotyped in three case/control cohorts of HIV-1 exposed seronegative individuals (HESN) and HIV-1 infected subjects from Italy, Peru, and Colombia; data from a Thai population were retrieved from the literature. Across all cohorts, homozygosity for the short TIM-1 allele was more common in HESNs than in HIV-1 infected subjects. A meta-analysis of the four association analyses yielded a p value of 0.005. In vitro infection assays of CD4+ T lymphocytes indicated that homozygosity for the short allele is associated with lower rate of HIV-1 replication. These results suggest that the deletion allele protects from HIV-1 infection with a recessive effect., (Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

RIG-I-like receptors (RLRs) are nucleic acid sensors that activate antiviral innate immune response. These molecules recognize diverse non-self RNA substrates and are antagonized by several viral inhibitors. We performed an evolutionary analysis of RLR genes (RIG-I, MDA5, and LGP2) in mammals. Results indicated that purifying selection had a dominant role in driving the evolution of RLRs. However, application of maximum-likelihood analyses identified several positions that evolved adaptively. Positively selected sites are located in all domains of MDA5 and RIG-I, whereas in LGP2 they are confined to the helicase domain. In both MDA5 and RIG-I, the linkers separating the caspase activation and recruitment domain and the helicase domain represented preferential targets of positive selection. Independent selective events in RIG-I and LGP2 targeted the corresponding site (Asp421 and Asp179, respectively) within a protruding α-helix that grips the V-shaped structure formed by the pincer. Most of the positively selected sites in MDA5 are in regions unique to this RLR, including a characteristic insertion within the helicase domain. Additional selected sites are located at the contact interface between MDA5 monomers, in spatial proximity to a positively selected human polymorphism (Arg843His) and immediately external to the parainfluenza virus 5 V protein binding region. Structural analyses suggested that the positively selected His834 residue is involved in parainfluenza virus 5 V protein binding. Data herein suggest that RLRs have been engaged in host-virus genetic conflict leading to diversifying selection and indicate parallel evolution at the same site in RIG-I and LGP2, a position likely to be of central importance in antiviral responses., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Selenoprotein N-related myopathy (SEPN1-RM) is an early-onset muscle disorder that can manifest clinically as congenital muscular dystrophy with spinal rigidity and can result in specific pathological entities such as multiminicore disease, desmin-related myopathy with Mallory body-like inclusions, and congenital fiber-type disproportion. Here we describe the clinical, histopathological, muscle magnetic resonance imaging (MRI) and genetic findings of three Italian SEPN1-RM families. Proband 1 is a 31-year-old female who was floppy at birth and developed axial and mild lower limb-girdle weakness. The second proband is a 13-year-old boy with RSMD1. Probands 3 and 4 were brothers showing clinical phenotype of congenital myopathy. Muscle MRI demonstrated selective involvement of sartorius, gluteal muscles and distal gastrocnemius and sparing of rectus femoris and gracilis. Muscle histopathology showed in proband 1 myopathic changes with mild connective tissue increase and some fibres lacking the Z-line, while probands 2 and 3 had multiminicores. SEPN1 gene analysis revealed five mutations, three of which are novel. Proband 1 was a compound heterozygote for a 92-bp (exon 1) and a 1-bp deletion (exon 9); proband 2 had a 99-bp deletion and a 10-bp duplication in exon 1, and proband 3 presented a novel homozygous mutation in intron 10 acceptor splice site., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Congenital muscular dystrophies (CMD) are autosomal recessive infantile disorders characterized by dystrophic changes at muscle biopsy and contractures. Central nervous system (CNS) abnormalities associated with mental retardation are often present. We describe a patient affected with muscle weakness, psychomotor developmental delay and normal brain MRI. Muscle biopsy showed complete absence of the alpha-dystroglycan (DG) glycosylated epitope and preservation of alpha-dystroglycan (alpha-DG) protein core. The analysis of FKRP, LARGE, POMT1 and POMGnT1 genes did not show any pathogenic mutations, suggesting that at least another gene may account for CMD with secondary glycosylated alpha-DG deficiency.

The human transcriptome is constituted of a great majority of intron-containing and a minority of intron-lacking mRNAs; given the different processing these transcripts undergo, they are expected to carry, intermingled with coding properties, very different editing information. Here we applied a computational approach to compare intronless and intron-containing coding sequences. Hexamer composition comparison allowed the definition of over- and under-represented motifs in intronless genes; surprisingly, experimental testing revealed that intron-lacking coding sequences are enriched rather than depleted in elements with splicing enhancement ability. Similarly, we show evidence that intronless transcripts display a significantly higher frequency of both shuttling and non-shuttling SR protein binding sites compared to intron-containing sequences. These observations suggest that SR proteins (and possibly other splicing factors) play a role in cellular processes distinct from splicing.

Despite promoter tissue specificity, up-regulation of the brain and Purkinje cell type dystrophin isoforms was described in skeletal muscle of X-linked dilated cardiomyopathy (XLDCM) and BMD affected individuals. An extended population of 11 Duchenne muscular dystrophy (DMD) and 11 Becker muscular dystrophy (BMD) patients was investigated to determine whether ectopic muscle expression of the two full-length non-muscular isoforms is a common event in dystrophinopathies and if it has functional significance. Up-regulation of the two non-muscle-specific isoforms was detected in four DMD patients but in none of the BMD affected individuals or non-dystrophic controls. This is the first report of an expression of these two isoforms in DMD skeletal muscle. Ectopic expression is not confined to regenerating or revertant fibers and does not correlate with age at biopsy, clinical phenotype, cardiac involvement, deletion size or location. We consider that muscle ectopic expression of the brain and Purkinje cell-type isoforms has no favorable prognostic significance in DMD and BMD patients.

Xotx1 is a Xenopus homeobox gene related to the Drosophila gene orthodenticle (otd). We previously reported that Xotx1 transcripts are already present in unfertilized egg. Here we report that maternal Xotx1 mRNA is vegetally localized during oogenesis. In stage II oocytes Xotx1 transcripts are localized within the mitochondrial cloud, in a perinuclear position; later on, they are translocated to the vegetal cortex within the mitochondrial cloud. We also observed that in stage III oocytes the expression domain of Wnt11 is contained within the one of Xotx1 while, at stage IV, the Xotx1 expression domain is contained within the one of Vg1.