Rosa laevigata Polysaccharides Ameliorate Dextran Sulfate Sodium-Induced Ulcerative Colitis of Beagles through Regulating Gut Microbiota.

Rosa laevigata Michx. polysaccharides (RLP) have been demonstrated to possess antioxidant and anti-inflammatory properties. However, the mechanisms and efficacy of these polysaccharide components in preventing ulcerative colitis (UC) remain to be elucidated. The efficacy and mechanisms of RLP were investigated in a study that utilized healthy adult beagles to establish a UC model, considering the similarities in gut microbiota between humans and dogs. In the study, the beagle model induced by sodium dextran sulfate exhibited typical symptoms of ulcerative colitis, such as weight loss and diarrhea. All these symptoms and changes were significantly ameliorated through oral supplementation of RLP. Additionally, microbial community analysis based on the 16S rDNA gene revealed that RLP alleviated UC by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. In conclusion, our study has provided that RLP effectively alleviated colitis by preserving the intestinal barrier and regulating the gut microbiota composition.

Application Value of Flexible Endoscopic Examination of Swallowing in Acute Stoke Patients With Dysphagia.

BACKGROUND: The aim was to study the application value of flexible endoscopic examination of swallowing (FEES) for the aspiration screening, the diagnosis of dysphagia and evaluation of the therapeutic effect in acute stoke patients with dysphagia. METHODS: A total of 525 patients with acute stoke who were hospitalized from October 2015 to January 2021 in the Rehabilitation Medicine Department of our hospital underwent FEES for analyzing the characteristic performance. Twenty-one cases of them were examined by video fluoroscopic swallow study and compared with the results of FEES for evaluating the reliability of the FEES, the reliability of diagnosis of dysphagia, and the consistency of the 2 methods. The effect of rehabilitation was evaluated by comparing the FEES test results before and after treatment. RESULTS: In 525 patients, the FEES revealed 378 cases of aspiration (139 cases were silent aspiration), showing a higher detection rate than water swallow test. Patients with potential cricopharyngeus achalasia got the same results through both of examinations. FEES can provide more positive indicators, guide clinical rehabilitation treatment and objectively assess the effect of rehabilitation. CONCLUSIONS: Acute stoke patients with dysphagia have characteristic pharyngeal and laryngeal performance. FEES is simple to operate and has high application value in the diagnosis and treatment of dysphagia.

Is the Fate of Clinical Candidate Arry-520 Already Sealed? Predicting Resistance in Eg5-Inhibitor Complexes.

Arry-520 is an advanced drug candidate from the Eg5 inhibitor class undergoing clinical evaluation in patients with relapsed or refractory multiple myeloma. Here, we show by structural analysis that Arry-520 binds stoichiometrically to the motor domain of Eg5 in the conventional allosteric loop L5 pocket in a complex that suggests the same structural mechanism as other Eg5 inhibitors. We have previously shown that acquired resistance through mutations in the allosteric-binding site located at loop L5 in the Eg5 structure appears to be independent of the inhibitors' scaffold, which suggests that Arry-520 will ultimately have the same fate. When Arry-520 was assessed in two cell lines selected for the expression of either Eg5(D130A) or Eg5(L214A) STLC-resistant alleles, mutations previously shown to convey resistance to this class of inhibitors, it was inactive in both. Surprisingly, when the cells were challenged with ispinesib, another Eg5 inhibitor, the Eg5(D130A) cells were resistant, but those expressing Eg5(L214A) were strikingly sensitive. Molecular dynamics simulations suggest that subtle differences in ligand binding and flexibility in both compound and protein may alter allosteric transmission from the loop L5 site that do not necessarily result in reduced inhibitory activity in mutated Eg5 structures. Although we predict that cells challenged with Arry-520 in the clinical setting are likely to acquire resistance through point mutations in the Eg5-binding site, the data for ispinesib suggest that this resistance mechanism is not scaffold independent as previously thought, and new inhibitors can be designed that retain inhibitory activity in these resistant cells.

Autosomal recessive non-syndromic hearing loss is caused by novel compound heterozygous mutations in TMC1 from a Tibetan Chinese family.

OBJECTIVES: Hearing loss is the most common sensory disorder worldwide. Biallelic mutations in 42 different genes have been identified as associated with autosomal recessive non-syndromic hearing loss (ARNSHL). One of the common genes responsible for ARNSHL is TMC1. TMC1 mutations have been reported to cause non-syndromic hearing loss in a variety of populations. The current study is designed to investigate mutations prevalent among Chinese ethnic groups with ARNSHL. METHODS: Targeted exome sequencing (TES) was employed to study the genetic causes of two siblings with ARNSHL in a Tibetan Chinese family. Variants identified by TES were further confirmed by Sanger sequencing. RESULTS: We identified two distinct variants in the TMC1 gene in two deaf siblings of one Tibetan Chinese family using TES. Both siblings inherited a paternal allele containing a deletion of c.1396_1398AAC (p.Asn466del) and a maternal allele containing an insertion of c.2210_2211insCT (p.Glu737HisfsX2). The former disrupts a highly conserved residue in the large intracellular loop domain adjacent to the fourth transmembrane domain, and the latter causes a truncation of a portion of the C-terminal domain. These variants were compound heterzygous and segregated with the hearing impairment in this family. CONCLUSION: The novel compound heterozygous mutant alleles of TMC1 identified in this study were responsible for the ARNSHL in this Tibetan Chinese family. Although compound heterozygous mutations in TMC1 occurring in different TMC1 domains have been previously described in Han Chinese; this result suggests that the TMC1 variants contributing to hereditary deafness in Chinese populations may be more complex than initially assumed and that sequence-based diagnostics will be required for a comprehensive evaluation of ARNSHL.