Therapeutic effect of fecal microbiota transplantation on chronic unpredictable mild stress-induced depression

Background and objectiveDepression is a complex neuropsychiatric disease with extensive morbidity. Its pathogenesis remains unclear, and it is associated with extremely low rates of cure and complete remission. It is vital to study the pathogenesis of depression to develop effective treatments. This study aimed to explore the therapeutic effects and mechanisms of fecal microbiota transplantation (FMT) for the treatment of depression in rats.MethodsThirty Sprague-Dawley (SD) rats were randomly divided into three groups: control, chronic unpredictable mild stress (CUMS) to model depression, and CUMS+FMT. For the CUMS and CUMS+FMT groups, after CUMS intervention (four weeks), the rats were given normal saline or FMT (once/week for three weeks), respectively. Behavior, colonic motility, 16S rDNA amplicon sequencing, and untargeted metabolomics on fecal samples were compared between the three rat groups. The following markers were analyzed: 5-hydroxytryptamine (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), and brain-derived neurotrophic factor (BDNF) levels in the hippocampus; glucagon-like peptide 1 (GLP-1), lipopolysaccharide (LPS), and interleukin (IL)-6 levels in the serum; and GLP-1, GLP-1 receptor (GLP-1R), and serotonin 4 receptor (5-HT4R) levels in colonic tissues.ResultsFMT improved symptoms of depression and colonic motility in rats exposed to CUMS. The expression levels of 5-HT, GABA, BDNF, and other biochemical indices, significantly differed among the three groups. Meanwhile, the intestinal microbiota in the CUMS+FMT group was more similar to that of the control group with a total of 13 different fecal metabolites.ConclusionFMT exerted antidepressant effects on CUMS-induced depression in rats, and the mechanism involved various neurotransmitters, inflammatory factors, neurotrophic factors, and glucagon-like peptides

Multiple imaging modality-guided radiofrequency ablation combined with transarterial chemoembolization for hepatocellular carcinoma in special locations

PURPOSEWe aimed to evaluate the safety and effectiveness of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) guided by multiple imaging modalities for hepatocellular carcinomas (HCCs) in special (i.e., high-risk or unfavorable) locations compared with those in conventional locations.METHODSA total of 122 HCC patients were enrolled, including 85 patients (69.7%) with HCC in conventional locations and 37 (30.3%) with HCC in special locations. The clinical data, overall survival (OS), progression-free survival (PFS), and procedure-related adverse events were analyzed.RESULTSRFA combined with TACE was successfully performed in all patients. Three complications (2.5%) occurred, with no significant difference between the conventional (n=1, 1.2%) and special (n=2, 5.4%) locations (P = 0.218). Complete tumor necrosis rate was not significantly different between the conventional (n=73, 85.9%) and special (n=34, 91.9%) locations at one-month imaging (P = 0.353). After a follow-up of 3–48 months, the PFS was 17 months for patients with HCC in conventional locations and 14 months for patients with HCC in special locations; one-year PFS rate was 68.1% in the conventional location group, not significantly (P = 0.741) different from 59.1% in the special location group. The OS was 28 months in the conventional location group while 32 months in the special location group. The cumulative one- and two-year OS rates were 89.9% and 63.3%, respectively, in the conventional location group, not significantly different from 96.3% and 65% in the special location group (P = 0.273). Age (P = 0.043) and tumor size (P < 0.001) were significant prognostic factors for OS, and tumor size (P < 0.001) was the only significant prognostic factor for PFS.CONCLUSIONRFA guided by multiple imaging modalities combined with TACE may be safe and effective for treating HCCs in special locations

Dense infraspecific sampling reveals cryptic differentiation in the enigmatic hemiparasitic love vine Cassytha filiformis (Lauraceae)

Species delimitation remains a challenge worldwide, especially in highly diverse tropical and subtropical regions. Here, we use an integrative approach that combines morphology, phylogenomics, and species distribution modeling (SDM) to clarify the cryptic differentiation within the enigmatic hemiparasitic love vine Cassytha filiformis (Lauraceae) in China and adjacent regions. We generated complete plastid genomes and nuclear ribosomal sequences for diverse samples from across the species range and compared results with previously published plastid data, recovering two well-supported monophyletic clades. Further, the analysis revealed significant differences in two morphological characters and SDM, indicating distinct environmental factors influencing their distributions. Fossil-calibrated analyses to estimate the origins and diversification patterns for the cryptic species gave divergence age estimates corresponding to the Oligo-Miocene; a period of new ecological opportunities associated with the prevailing East Asian monsoon. Multivariate analyses support the conclusion that southern China and adjacent regions have a different, previously unknown, cryptic lineage of C. filiformis. Our study highlights the importance of using multivariate approach to characterize plant species, as well as the significant role that past climatic changes have played in driving speciation in parasitic plants in tropical and subtropical zones.</p

Study of Local Inner Ear Gene Therapy for Controlling Autoimmune Sensorineural Hearing Loss

Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vectorexpressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groups ( &lt; 0.05). Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases

A Protective Mechanism against Antibiotic-Induced Ototoxicity: Role of Prestin

Hearing loss or ototoxicity is one of the major side effects associated with the use of the antibiotics, particularly aminoglycosides (AGs), which are the most commonly used antibiotics worldwide. However, the molecular and cellular events involved in the antibiotic-induced ototoxicity remains unclear. In the present study, we test the possibility that prestin, the motor protein specifically expressed in the basolateral membrane of outer hair cells (OHCs) in the cochlea with electromotility responsible for sound amplification, may be involved in the process of AG-induced apoptosis in OHCs. Our results from both mice model and cultured cell line indicate a previously unexpected role of prestin, in mediating antibiotic-induced apoptosis, the effect of which is associated with its anion-transporting capacity. The observed downregulation of prestin mRNA prior to detectable apoptosis in OHCs and hearing loss in the antibiotic-treated mice is interesting, which may serve as a protective mechanism against hearing loss induced by AGs in the early stage

Flattening filter-free accelerators: a report from the AAPM Therapy Emerging Technology Assessment Work Group.

This report describes the current state of flattening filter-free (FFF) radiotherapy beams implemented on conventional linear accelerators, and is aimed primarily at practicing medical physicists. The Therapy Emerging Technology Assessment Work Group of the American Association of Physicists in Medicine (AAPM) formed a writing group to assess FFF technology. The published literature on FFF technology was reviewed, along with technical specifications provided by vendors. Based on this information, supplemented by the clinical experience of the group members, consensus guidelines and recommendations for implementation of FFF technology were developed. Areas in need of further investigation were identified. Removing the flattening filter increases beam intensity, especially near the central axis. Increased intensity reduces treatment time, especially for high-dose stereotactic radiotherapy/radiosurgery (SRT/SRS). Furthermore, removing the flattening filter reduces out-of-field dose and improves beam modeling accuracy. FFF beams are advantageous for small field (e.g., SRS) treatments and are appropriate for intensity-modulated radiotherapy (IMRT). For conventional 3D radiotherapy of large targets, FFF beams may be disadvantageous compared to flattened beams because of the heterogeneity of FFF beam across the target (unless modulation is employed). For any application, the nonflat beam characteristics and substantially higher dose rates require consideration during the commissioning and quality assurance processes relative to flattened beams, and the appropriate clinical use of the technology needs to be identified. Consideration also needs to be given to these unique characteristics when undertaking facility planning. Several areas still warrant further research and development. Recommendations pertinent to FFF technology, including acceptance testing, commissioning, quality assurance, radiation safety, and facility planning, are presented. Examples of clinical applications are provided. Several of the areas in which future research and development are needed are also indicated