Genetic assessment and candidate genes identification for breed-specific characteristics of Qingyuan partridge chicken based on runs of homozygosity.

BACKGROUND: Several core breeding and supporting lines of the Qingyuan partridge chicken, a representative local chicken breed in China, have been developed over 20 years. Consequently, its economic traits related to growth and reproduction have been significantly improved by breeding selection and commercial utilization, but some characteristic traits, such as partridge feathers, high meat quality and sufficient flavor, have always been retained. However, effective methods for genetic assessment and functional gene exploration of similar trait groups are lacking. The presence of identical haplotype fragments transmitted from parent to offspring results in runs of homozygosity (ROH), which offer an efficient solution. In this study, genomes of 134 Qingyuan partridge chickens representing two breeding populations and one preserved population were re-sequenced to evaluate the genetic diversity and explore functional genes by analyzing the diversity, distribution, and frequency of ROH. RESULTS: The results showed a low level of genomic linkage and degree of inbreeding within both the bred and preserved populations, suggesting abundant genetic diversity and an adequate genetic potential of the Qingyuan partridge chicken. Throughout the long-term selection process, 21 genes, including GLI3, ANO5, BLVRA, EFNB2, SLC5A12, and SVIP, associated with breed-specific characteristics were accumulated within three ROH islands, whereas another 21 genes associated with growth traits including IRX1, IRX2, EGFR, TPK1, NOVA1, BDNF and so on were accumulated within five ROH islands. CONCLUSIONS: These findings provide new insights into the genetic assessment and identification of genes with breed-specific and selective characteristics, offering a solid genetic basis for breeding and protection of Qingyuan partridge chickens.

Semiconducting Polymer Dots for Dual-Wavelength Differential Background-Suppressed Photoacoustic Imaging.

Photoacoustic imaging (PAI) can sensitively detect regions and substances with strong optical absorption, which means that diseased tissue can be imaged with high contrast in the presence of surrounding healthy tissue through the photoacoustic effect. However, its signal intensity and resolution may be limited by background signals generated by endogenous chromophores such as melanin and hemoglobin. A feasible method for practical application of this so-called background-suppressed PAI is still lacking. In this work, a dual-wavelength differential background noise-suppressed photoacoustic tomography is developed based on organic semiconducting polymer dots (Pdots). The Pdots have a strong absorption peak at 945 nm, and then the absorption decreases sharply with the increase of wavelength, and the absorption intensity drops to only about a quarter of the original value at 1050 nm. The present system significantly suppresses the strong background noise of blood through dual-wavelength differential PAI, enabling precise monitoring of the distribution information of theranostic agents in diseased tissues. The signal-to-noise ratio of the theranostic agent distribution map is increased by about 20 dB. This work provides a platform for real-time and accurate monitoring of tumors and drugs, which helps avoid damage to healthy tissue during treatment and has clinical significance in cancer treatment.

Dynamic monitoring of oxygen partial pressure in photodynamic therapy using pump-probe-based photoacoustic tomography.

Pump-probe-based photoacoustic tomography (PP-PAT) is an innovative and promising molecular imaging technique. In this study, we utilized PP-PAT for the first time, to the best of our knowledge, to monitor the dynamics of oxygen partial pressure (pO2) within murine tumors during photodynamic therapy (PDT) with methylene blue (MB). We developed, to our knowledge, a novel two-step fitting method to simultaneously map both the pO2 and the MB concentrations and implemented it with mexCuda to accelerate the pixel-wise-based calculation. The results demonstrated a penetration depth of up to 5 mm and revealed a significant decrease in pO2 during the PDT process, consistent with existing research findings. This study suggests that PP-PAT has the potential to become a valuable tool for intraoperative monitoring of PDT, thereby enhancing therapeutic efficacy.

SOSNet: Real-Time Small Object Segmentation via Hierarchical Decoding and Example Mining.

Real-time semantic segmentation plays an important role in auto vehicles. However, most real-time small object segmentation methods fail to obtain satisfactory performance on small objects, such as cars and sign symbols, since the large objects usually tend to devote more to the segmentation result. To solve this issue, we propose an efficient and effective architecture, termed small objects segmentation network (SOSNet), to improve the segmentation performance of small objects. The SOSNet works from two perspectives: methodology and data. Specifically, with the former, we propose a dual-branch hierarchical decoder (DBHD) which is viewed as a small-object sensitive segmentation head. The DBHD consists of a top segmentation head that predicts whether the pixels belong to a small object class and a bottom one that estimates the pixel class. In this situation, the latent correlation among small objects can be fully explored. With the latter, we propose a small object example mining (SOEM) algorithm for balancing examples between small objects and large objects automatically. The core idea of the proposed SOEM is that most of the hard examples on small-object classes are reserved for training while most of the easy examples on large-object classes are banned. Experiments on three commonly used datasets show that the proposed SOSNet architecture greatly improves the accuracy compared to the existing real-time semantic segmentation methods while keeping efficiency. The code will be available at https://github.com/StuLiu/SOSNet.

Epigenetic regulation and therapeutic targets in the tumor microenvironment.

The tumor microenvironment (TME) is crucial to neoplastic processes, fostering proliferation, angiogenesis and metastasis. Epigenetic regulations, primarily including DNA and RNA methylation, histone modification and non-coding RNA, have been generally recognized as an essential feature of tumor malignancy, exceedingly contributing to the dysregulation of the core gene expression in neoplastic cells, bringing about the evasion of immunosurveillance by influencing the immune cells in TME. Recently, compelling evidence have highlighted that clinical therapeutic approaches based on epigenetic machinery modulate carcinogenesis through targeting TME components, including normalizing cells' phenotype, suppressing cells' neovascularization and repressing the immunosuppressive components in TME. Therefore, TME components have been nominated as a promising target for epigenetic drugs in clinical cancer management. This review focuses on the mechanisms of epigenetic modifications occurring to the pivotal TME components including the stroma, immune and myeloid cells in various tumors reported in the last five years, concludes the tight correlation between TME reprogramming and tumor progression and immunosuppression, summarizes the current advances in cancer clinical treatments and potential therapeutic targets with reference to epigenetic drugs. Finally, we summarize some of the restrictions in the field of cancer research at the moment, further discuss several interesting epigenetic gene targets with potential strategies to boost antitumor immunity.

Feature Consistency-Based Prototype Network for Open-Set Hyperspectral Image Classification.

Hyperspectral image (HSI) classification methods have made great progress in recent years. However, most of these methods are rooted in the closed-set assumption that the class distribution in the training and testing stages is consistent, which cannot handle the unknown class in open-world scenes. In this work, we propose a feature consistency-based prototype network (FCPN) for open-set HSI classification, which is composed of three steps. First, a three-layer convolutional network is designed to extract the discriminative features, where a contrastive clustering module is introduced to enhance the discrimination. Then, the extracted features are used to construct a scalable prototype set. Finally, a prototype-guided open-set module (POSM) is proposed to identify the known samples and unknown samples. Extensive experiments reveal that our method achieves remarkable classification performance over other state-of-the-art classification techniques.

Photoacoustic Microscopic Imaging of Cerebral Vessels for Intensive Monitoring of Metabolic Acidosis.

PURPOSE: Metabolic acidosis as one of the most common perioperative complications has been associated with increased risks for poor prognosis. Routine monitoring methods include blood gas analysis and electrocardiogram, which are limited by time delay effects. And the existing intravital imaging modalities are difficult to achieve in one step. Here, we present a dual-wavelength photoacoustic imaging approach to overcome this dilemma. The aim of this study was to develop a rapid approach for intensive monitoring of acid-base imbalance and cerebral oxygen metabolism. PROCEDURES: We characterized the cerebrovascular structure by label-free dual-wavelength (532 and 559 nm) photoacoustic microscopy in healthy and diabetic mouse models with metabolic acidosis. Concurrently, we developed a single-vessel analysis method to accurately delineate the differential responses of small vessels and quantify the cerebral oxygenation following experimental alteration of pH. RESULTS: We demonstrated that there was an increasing trend in changes of vascular measurements (density, diameter, and relative hemoglobin concentration) and cerebral microvascular oxygen metabolism with the aggravation of acidosis. Furthermore, we established a clinical nomogram for the diagnosis of disease severity and yielded good discrimination ability with area under the curve of 0.920-0.967 and accuracy of 81.9-93.0%. The nomogram was also validated well in the diabetic mouse model with metabolic acidosis. CONCLUSIONS: Our photoacoustic imaging approach has great potential for rapid detection of metabolic acidosis and brain oxygen metabolism, which could potentially be applied as a bedside monitoring method for brain protection and timely treatment of acid-base abnormalities.

Alkaline earth metals for osteogenic scaffolds: From mechanisms to applications.

Regeneration of bone defects is a significant challenge today. As alternative approaches to the autologous bone, scaffold materials have remarkable features in treating bone defects; however, the various properties of current scaffold materials still fall short of expectations. Due to the osteogenic capability of alkaline earth metals, their application in scaffold materials has become an effective approach to improving their properties. Furthermore, numerous studies have shown that combining alkaline earth metals leads to better osteogenic properties than applying them alone. In this review, the physicochemical and physiological characteristics of alkaline earth metals are introduced, mainly focusing on their mechanisms and applications in osteogenesis, especially magnesium (Mg), calcium (Ca), strontium (Sr), and barium (Ba). Furthermore, this review highlights the possible cross-talk between pathways when alkaline earth metals are combined. Finally, some of the current drawbacks of scaffold materials are enumerated, such as the high corrosion rate of Mg scaffolds and defects in the mechanical properties of Ca scaffolds. Moreover, a brief perspective is also provided regarding future directions in this field. It is worth exploring that whether the levels of alkaline earth metals in newly regenerated bone differs from those in normal bone. The ideal ratio of each element in the bone tissue engineering scaffolds or the optimal concentration of each elemental ion in the created osteogenic environment still needs further exploration. The review not only summarizes the research developments in osteogenesis but also offers a direction for developing new scaffold materials.

Depression in Chinese Patients with Cleft Lip and/or Palate: A Preliminary Study.

(1) Objectives: To investigate the difference in prevalence of depression between patients with CL/P (cleft lip and/or palate) and analyze the possible demographic factors that affect the prevalence of depression in Chinese patients with CL/P. (2) Methods: Patients with CL (cleft lip only), CP (cleft palate), and CLP (cleft lip and palate) were included in the study group. Non-CL/P individuals were included in the control group. The Patient Health Questionnaire (PHQ-9) was used to screen the depression of Chinese patients with CL/P. The different proportions of different depression groups between the CL/P group and the control groups were tested by the Fisher-Freeman-Halton test and Bonferroni correction. The scores between the study groups and the control group were analyzed by one-way ANOVA. In the study groups, demographic and clinical data of the patients, including diagnosis (CL, CP, CLP), gender, age, the only child or not, and region were collected to analyze whether they were the possible factors affecting depression through one-way independent-samples t-test. Pearson correlation analysis was used to analyze the correlation between monthly family income and depression. (3) Results: 111 and 80 valid questionnaires were collected from the study and control groups, respectively. The mean PHQ-9 score of the study group (5.459 ± 6.082) was relatively higher than the control group (4.362 ± 3.384), and the difference in proportions of depression groups was statistically significant between the CL/P group and the control group (p = 0.01), especially in the mild depression (p < 0.05) and moderately severe depression groups (p < 0.05). Statistically significant differences in PHQ-9 scores were observed between the individuals of different genders (p = 0.036) and ages (p = 0.007) in patients with CL/P, the individuals who were the only child or not in patients with CL (p = 0.007), and the individuals of different ages in patients with CP (p = 0.016). (4) Conclusions: The prevalence of depression in Chinese patients with CL/P was different compared with those without CL/P, while gender, age, the only child or not, and region played significant roles in affecting depression psychology.

Spectroscopic photoacoustic/ultrasound/optical-microscopic multimodal intrarectal endoscopy for detection of centimeter-scale deep lesions.

The inadequacy of existing colorectal imaging tools has significantly obstructed the efficient detection of colorectal cancer. To address this issue, this work presents the cross-scale endoscopic imaging of rectal tumors with a combined photoacoustic/ultrasound tomography system and wide-field optical microscopy. This multimodal system combines the merits of centimeter-scale deep penetration, multi-spectral imaging, cross-scale imaging ability, low system cost, and 360° view in a single modality. Results indicated that the proposed system could reliably depict the location of the cancer invasion depth spectroscopically with indocyanine green The tumor angiogenesis can be well identified in the wide-field optical imaging mode, which helps to localize the tumors and guide the following photoacoustic/ultrasound scan. This work may facilitate the accurate characterization of colorectal cancer and promote the clinical translation of photoacoustic-based colorectal endoscopy.

Inhibiting microRNA-142-5p improves learning and memory in Alzheimer's disease rats via targeted regulation of the PTPN1-mediated Akt pathway.

OBJECTIVE: MicroRNAs (miRNAs) have been recognized as possible biomarkers for Alzheimer's disease (AD). MiR-142-5p has been reported to be abnormally expressed in brain tissues. However, the role of miR-142-5p in AD pathogenesis keeps unclear. This study aimed to investigate the effect of miR-142-5p on the learning and memory of AD rats via regulation of protein tyrosine phosphatase nonreceptor type 1 (PTPN1)-mediated protein kinase B (Akt) pathway. METHODS: The AD model was established by injection of Aß1-42 oligomer once into the lateral ventricle of rats, and the spatial learning and memory ability of rats was measured. AD rats were injected with miR-142-5p or PTPN1 vectors to explore their functions in inflammation, Aß, p-tau protein, apoptosis in brain tissues, and the effects on Akt pathway. The targeting relationship between miR-142-5p and PTPN1 was detected. RESULTS: Overexpressed miR-142-5p, down-regulated PTPN1 and inactivated Akt pathway were exhibited in AD. MiR-142-5p targeted PTPN1 to mediate Akt pathway. Reduced miR-142-5p and elevated PTPN1 improved the behavior of AD rats. MiR-142-5p targeted PTPN1 to effectively inhibit Aß formation and abnormal phosphorylation of p-tau protein, suppress the inflammation in the brain tissues of AD rat, and improve the survival rate of brain tissue cells. MiR-142-5p regulated PTPN1 to activate the Akt pathway, further inhibiting the apoptosis of brain neurons in AD rats. CONCLUSION: Down-regulating miR-142-5p targets PTPN1 to activate Akt pathway, thus improving the learning and memory of AD rats and playing an anti-AD role.

Early fecal microbiota transplantation from high abdominal fat chickens affects recipient cecal microbiome and metabolism.

Abdominal fat deposition (AFD) in chickens is closely related to the gut microecological balance. In this study, the gut microbiota from high-AFD chickens was transplanted into the same strain of 0-day-old chicks via fecal microbiota transplantation (FMT). The FTM from chickens with high AFD had no obvious effects on growth traits, adult body weight, carcass weight, abdominal fat weight, and abdominal fat percentage, but did reduce the coefficient of variation of AFD traits. FMT significantly decreased cecal microbiome richness, changed the microbiota structure, and regulated the biological functions associated with energy metabolism and fat synthesis. Additionally, the cecal metabolite composition and metabolic function of FMT recipient chickens were also significantly altered from those of the controls. Transplantation of high-AFD chicken gut microbiota promoted fatty acid elongation and biosynthesis and reduced the metabolism of vitamins, steroids, and carbohydrates in the cecum. These findings provide insights into the mechanisms by which chicken gut microbiota affect host metabolic profiles and fat deposition.

The correlation between OSA-related quality of life and two mental statuses in adolescent Chinese patients with cleft palate: A comprehensive study.

Objectives: To analyze obstructive sleep apnea (OSA)-related quality of life (QoL), the statuses of depression and anxiety, and to reveal the correlation between OSA-related QoL and two mental statuses in Chinese adolescent patients with cleft palate (CP). Methods: The Obstructive Sleep Apnea Questionaire-18 (OSA-18), the Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9) were applied to assess OSA-related QoL and the statuses of anxiety and depression in Chinese adolescent patients with CP, respectively. Non-CP adolescents were also included in the control group. OSA-related QoL and the two mental statuses were compared between the study and control groups. The correlation between the OSA-related QoL and two mental statuses was estimated in Chinese adolescent patients with CP. Results: A total of 8.7% patients showed a moderate or high impact of OSA on QoL, while all the adolescents from the control group showed little impact. The mean total OSA-18 score of the study group (36.261 ± 13.500) was significantly higher than the control (28.435 ± 8.934). The mean PHQ-9 scores of the study group and the control group were statistically different (3.957 vs. 2.113). The GAD-7 score in the study group was slightly higher than the control group (3.043 vs. 2.194), while the proportion of moderate-severe anxiety in the study group was relatively larger than that in the control group (6.5% vs. 1.6%). Moreover, there was a positive correlation between the OSA-related QoL and the statuses of anxiety and depression respectively, and the differences in GAD-7 and PHQ-9 scores between the moderate or high impact group and the little impact group were statistically significant. Conclusion: Chinese adolescents with CP reported a rate of moderate or high impact of OSA on QoL of 8.7%, which was significantly higher than adolescents without CP. The OSA-related QoL was worse and depression was severer in Chinese CP adolescents than in the control, while anxiety and depression in Chinese CP adolescents were associated with OSA-related QoL.

Multi-Scale Superpixel-Guided Structural Profiles for Hyperspectral Image Classification.

Hyperspectral image classification has received a lot of attention in the remote sensing field. However, most classification methods require a large number of training samples to obtain satisfactory performance. In real applications, it is difficult for users to label sufficient samples. To overcome this problem, in this work, a novel multi-scale superpixel-guided structural profile method is proposed for the classification of hyperspectral images. First, the spectral number (of the original image) is reduced with an averaging fusion method. Then, multi-scale structural profiles are extracted with the help of the superpixel segmentation method. Finally, the extracted multi-scale structural profiles are fused with an unsupervised feature selection method followed by a spectral classifier to obtain classification results. Experiments on several hyperspectral datasets verify that the proposed method can produce outstanding classification effects in the case of limited samples compared to other advanced classification methods. The classification accuracies obtained by the proposed method on the Salinas dataset are increased by 43.25%, 31.34%, and 46.82% in terms of overall accuracy (OA), average accuracy (AA), and Kappa coefficient compared to recently proposed deep learning methods.

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and its negative regulator kelch-like ECH-associated protein 1 (KEAP1) regulate various genes involved in redox homeostasis, which protects cells from stress conditions such as reactive oxygen species and therefore exerts beneficial effects on suppression of carcinogenesis. In addition to their pivotal role in cellular physiology, accumulating innovative studies indicated that NRF2/KEAP1-governed pathways may conversely be oncogenic and cause therapy resistance, which was profoundly modulated by epigenetic mechanism. Therefore, targeting epigenetic regulation in NRF2/KEAP1 signaling is a potential strategy for cancer treatment. In this paper, the current knowledge on the role of NRF2/KEAP1 signaling in cancer oxidative stress is presented, with a focus on how epigenetic modifications might influence cancer initiation and progression. Furthermore, the prospect that epigenetic changes may be used as therapeutic targets for tumor treatment is also investigated.

Anxiety in Chinese Patients With Cleft Lip and/or Palate: A Preliminary Study.

OBJECTIVES: To preliminarily analyze factors that affected the prevalence of anxiety in Chinese patients with cleft lip and/or palate (CL/P). METHODS: The Generalized Anxiety Disorder Scale (GAD-7) was used to screen anxiety in Chinese CL/P patients. Non-CL/P individuals were also included as the control group. Sociodemographic and clinical data consisting of diagnosis, gender, only child or not, monthly household income, and current family location were collected to analyze possible factors that could affect the anxiety of this patient population. RESULTS: One hundred forty-two and 78 valid questionnaires were collected from the study and control groups, respectively. The mean GAD-7 score of the study group (3.092 ± 3.381) was significantly lower than the control (3.987 ± 2.505). Moreover, the proportion of patients presenting with moderate-severe anxiety was larger in the study group than in the control group (6.6 vs. 0.0%). Statistically significant differences in GAD-7 scores were observed between the study and control groups when the patient was the only child, living in an urban area, or the monthly household income was between 1,000 and 5,000 yuan. CONCLUSION: Although the severity of anxiety in Chinese CL/P patients was not severer than those without CL/P, there was a relatively high incidence of moderate-severe anxiety in CL/P patients, while the only child, current family location and the monthly household income played significant roles in affecting anxiety psychology.

CircRNA-miRNA networks in regulating bone disease.

Circular RNA (circRNA) is a class of endogenous noncoding RNA (ncRNA), presenting as a special covalent closed loop without a 5' cap or 3' tail, maintaining resistance to RNA exonuclease and keeping high stability. Although lowly expressed in most situations, circRNA makes an active difference in regulating physiological or pathological processes by modulating gene expression by regulation of transcription, protein, and miRNA functions through various mechanisms in particular tissues. Recent studies have demonstrated the roles of the miRNA-circRNA network in the development of several bone diseases such as osteoporosis, a multiple-mechanism disease resulting from defective bone quality and low bone mass, osteoarthritis, whose main pathomechanism is inflammation and articular cartilage degradation, as well as osteosarcoma, known as one of the most common bone cancers. However, the specific mechanism of how circRNA along with miRNA influences those diseases is not well documented, showing potential for the development of new therapies for those bone diseases.

Specific Microbial Taxa and Functional Capacity Contribute to Chicken Abdominal Fat Deposition.

Genetically selected chickens with better growth and early maturation show an incidental increase in abdominal fat deposition (AFD). Accumulating evidence reveals a strong association between gut microbiota and adiposity. However, studies focusing on the role of gut microbiota in chicken obesity in conventional breeds are limited. Therefore, 400 random broilers with different levels of AFD were used to investigate the gut microbial taxa related to AFD by 16S rRNA gene sequencing of 76 representative samples, and to identify the specific microbial taxa contributing to fat-related metabolism using shotgun metagenomic analyses of eight high and low AFD chickens. The results demonstrated that the richness and diversity of the gut microbiota decrease as the accumulation of chicken abdominal fat increases. The decrease of Bacteroidetes and the increase of Firmicutes were correlated with the accumulation of chicken AFD. The Bacteroidetes phylum, including the genera Bacteroides, Parabacteroides, and the species, B. salanitronis, B. fragilis, and P. distasonis, were correlated to alleviate obesity by producing secondary metabolites. Several genera of Firmicutes phylum with circulating lipoprotein lipase activity were linked to the accumulation of chicken body fat. Moreover, the genera, Olsenella and Slackia, might positively contribute to fat and energy metabolism, whereas the genus, Methanobrevibacter, was possible to enhance energy capture, and associated to accumulate chicken AFD. These findings provide insights into the roles of the gut microbiota in complex traits and contribute to the development of effective therapies for the reduction of chicken fat accumulation.

Regenerating the Anal Sphincter: Cytokines, Stem Cells, or Both?

BACKGROUND: Healing of an anal sphincter defect at a time distant from injury is a challenge. OBJECTIVE: We aimed to investigate whether re-establishing stem cell homing at the site of an anal sphincter defect when cytokine expression has declined using a plasmid engineered to express stromal derived factor 1 with or without mesenchymal stem cells can improve anatomic and functional outcome. DESIGN: This was a randomized animal study. SETTINGS: Thirty-two female age- and weight-matched Sprague Dawley rats underwent 50% excision of the anal sphincter complex. Three weeks after injury, 4 interventions were randomly allocated (n = 8), including no intervention, 100-µg plasmid, plasmid and 800,000 cells, and plasmid with a gelatin scaffold mixed with cells. MAIN OUTCOME MEASURES: The differences in anal sphincter resting pressures just before and 4 weeks after intervention were used for functional analysis. Histology was analyzed using Masson staining. One-way ANOVA followed by the Tukey post hoc test was used for pressure and histological analysis. RESULTS: All 3 of the intervention groups had a significantly greater change in resting pressure (plasmid p = 0.009; plasmid + cells p = 0.047; plasmid + cells in scaffold p = 0.009) compared with the control group. The plasmid-with-cells group showed increased organization of muscle architecture and increased muscle percentage, whereas the control group showed disorganized architecture at the site of the defect. Histological quantification revealed significantly more muscle at the site of defect in the plasmid-plus-cells group compared with the control group, which had the least muscle. Quantification of connective tissue revealed significantly less fibrosis at the site of defect in the plasmid and plasmid-plus-cells groups compared with the control group. LIMITATIONS: Midterm evaluation and muscle morphology were not defined. CONCLUSIONS: At this midterm follow-up, local delivery of a stromal derived factor 1 plasmid with or without local mesenchymal stem cells enhanced anal sphincter muscle regeneration long after an anal sphincter injury, thereby improving functional outcome. See Video Abstract at http://links.lww.com/DCR/A324.

Electrical Stimulation Followed by Mesenchymal Stem Cells Improves Anal Sphincter Anatomy and Function in a Rat Model at a Time Remote From Injury.

BACKGROUND: We have explored cell-based therapy to aid anal sphincter repair, but a conditioning injury is required to direct stem cells to the site of injury because symptoms usually manifest at a time remote from injury. OBJECTIVE: We aimed to investigate the effect of local electrical stimulation followed by mesenchymal stem cell delivery on anal sphincter regeneration at a time remote from injury. DESIGN AND MAIN OUTCOME MEASURES: With the use of a rat model, electrical stimulation parameters and cell delivery route were selected based on in vivo cytokine expression and luciferase-labeled cell imaging of the anal sphincter complex. Three weeks after a partial anal sphincter excision, rats were randomly allocated to 4 groups based on different local interventions: no treatment, daily electrical stimulation for 3 days, daily stimulation for 3 days followed by stem cell injection on the third day, and daily electrical stimulation followed by stem cell injection on the first and third days. Histology-assessed anatomy and anal manometry evaluated physiology 4 weeks after intervention. RESULTS: The electrical stimulation parameters that significantly upregulated gene expression of homing cytokines also achieved mesenchymal stem cell retention when injected directly in the anal sphincter complex in comparison with intravascular and intraperitoneal injections. Four weeks after intervention, there was significantly more new muscle in the area of injury and significantly improved anal resting pressure in the group that received daily electrical stimulation for 3 days followed by a single injection of 1 million stem cells on the third day at the site of injury. LIMITATION: This was a pilot study and therefore was not powered for functional outcome. CONCLUSIONS: In this rat injury model with optimized parameters, electrical stimulation with a single local mesenchymal stem cell injection administered 3 weeks after injury significantly improved both new muscle formation in the area of injury and anal sphincter pressures.