Body Weight-Supported Treadmill Training Ameliorates Motoneuronal Hyperexcitability by Increasing GAD-65/67 and KCC2 Expression via TrkB Signaling in Rats with Incomplete Spinal Cord Injury.

Spasticity is a typical consequence after spinal cord injury (SCI). The critical reasons are reducing the synthesis of Gamma-Aminobutyric Acid (GABA), glycine and potassium chloride co-transporter 2 (KCC2) inside the distal spinal cord. The current work aimed to test whether exercise training could increase the expression of glutamic acid decarboxylase 65/67 (GAD-65/67, the key enzymes in GABA synthesis) and KCC2 in the distal spinal cord via tropomyosin-related kinase B (TrkB) signaling. The experimental rats were randomly assigned to the following five groups: Sham, SCI/phosphate-buffered saline (PBS), SCI-treadmill training (TT)/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG. After that, the model of T10 contusion SCI was used, then TrkB-IgG was used to prevent TrkB activity at 7 days post-SCI. Body weight-supported treadmill training started on the 8th day post-SCI for four weeks. The Hmax/Mmax ratio and the rate-dependent depression of H-reflex were used to assess the excitability of spinal motoneuronal networks. Western blotting and Immunohistochemistry techniques were utilized for measuring the expression of GAD-65, GAD-67, and KCC2. The findings revealed that exercise training could reduce motoneuronal excitability and boost GAD-65, GAD-67, and KCC2 production in the distal region of the spinal cord after SCI. The effects of exercise training were decreased after the TrkB signaling was inhibited. The present exploration demonstrated that exercise training increases GAD-65, GAD-67, and KCC2 expression in the spinal cord via TrkB signaling and that this method could also improve rats with motoneuronal hyperexcitability and spasticity induced by incomplete SCI.

Effects of Self-Assisted Shoulder Elevation of the Affected Side Combined with Balance Training on Associated Reactions of Upper Limb and Walking Function in Chronic Stroke Patients: A Randomized Controlled Trial.

BACKGROUND Associated reactions of the upper limb are frequently seen in stroke patients, especially during dynamic activities, such as walking. The aim of this study was to assess the effect of a method to inhibit the affected upper limb flexors combined with balance training on associated reactions of the affected upper limb and walking function in chronic stroke patients. MATERIAL AND METHODS 60 patients were randomly allocated into 3 groups (n=20 per group): control group (no upper limb intervention), back group (the unaffected hand assists the affected upper limb in the low back and keep it in an extended position) and shoulder elevation group using the inhibition method (the unaffected hand assists the affected shoulder to elevate above 90°). Before and after the four-week balance training, the surface electromyography was used to evaluate the rate of contraction of affected elbow flexors. Fugl-Meyer Assessment of Upper Extremity (FMA-UE), 10 Meter Walking Test (10MWT) and Barthel Index (BI) were used to measure functional status. RESULTS The shoulder elevation group had significant improvement in the percentage changes in the rate of contraction of the affected elbow flexors, 10WMT and FMA-UE (p<0.05) compared with back group and control group. We found no significant difference of 10WMT and FMA-UE between back group and control group. CONCLUSIONS The combination of the new inhibition method and the standing balance training could reduce the abnormal activity of affected elbow flexors during walking, increase walking speed, and improve the affected upper limb motor function.

Exercise training modulates glutamic acid decarboxylase-65/67 expression through TrkB signaling to ameliorate neuropathic pain in rats with spinal cord injury.

Neuropathic pain is one of the most frequently stated complications after spinal cord injury. In post-spinal cord injury, the decrease of gamma aminobutyric acid synthesis within the distal spinal cord is one of the main causes of neuropathic pain. The predominant research question of this study was whether exercise training may promote the expression of glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67, which are key enzymes of gamma aminobutyric acid synthesis, within the distal spinal cord through tropomyosin-related kinase B signaling, as its synthesis assists to relieve neuropathic pain after spinal cord injury. Animal experiment was conducted, and all rats were allocated into five groups: Sham group, SCI/PBS group, SCI-TT/PBS group, SCI/tropomyosin-related kinase B-IgG group, and SCI-TT/tropomyosin-related kinase B-IgG group, and then T10 contusion SCI model was performed as well as the tropomyosin-related kinase B-IgG was used to block the tropomyosin-related kinase B activation. Mechanical withdrawal thresholds and thermal withdrawal latencies were used for assessing pain-related behaviors. Western blot analysis was used to detect the expression of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-REB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. Immunohistochemistry was used to analyze the distribution of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord dorsal horn. The results showed that exercise training could significantly mitigate the mechanical allodynia and thermal hyperalgesia in post-spinal cord injury and increase the synthesis of brain-derived neurotrophic factor, tropomyosin-related kinase B, CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord. After the tropomyosin-related kinase B signaling was blocked, the analgesic effect of exercise training was inhibited, and in the SCI-TT/tropomyosin-related kinase B-IgG group, the synthesis of CREB, p-CREB, glutamic acid decarboxylase-65, and glutamic acid decarboxylase-67 within the distal spinal cord were also significantly reduced compared with the SCI-TT/PBS group. This study shows that exercise training may increase the glutamic acid decarboxylase-65 and glutamic acid decarboxylase-67 expression within the spinal cord dorsal horn through the tropomyosin-related kinase B signaling, and this mechanism may play a vital role in relieving the neuropathic pain of rats caused by incomplete SCI.

Decoding Calcium Signaling Dynamics during Drosophila Wing Disc Development.

The robust specification of organ development depends on coordinated cell-cell communication. This process requires signal integration among multiple pathways, relying on second messengers such as calcium ions. Calcium signaling encodes a significant portion of the cellular state by regulating transcription factors, enzymes, and cytoskeletal proteins. However, the relationships between the inputs specifying cell and organ development, calcium signaling dynamics, and final organ morphology are poorly understood. Here, we have designed a quantitative image-analysis pipeline for decoding organ-level calcium signaling. With this pipeline, we extracted spatiotemporal features of calcium signaling dynamics during the development of the Drosophila larval wing disc, a genetic model for organogenesis. We identified specific classes of wing phenotypes that resulted from calcium signaling pathway perturbations, including defects in gross morphology, vein differentiation, and overall size. We found four qualitative classes of calcium signaling activity. These classes can be ordered based on agonist stimulation strength Gαq-mediated signaling. In vivo calcium signaling dynamics depend on both receptor tyrosine kinase/phospholipase C γ and G protein-coupled receptor/phospholipase C ß activities. We found that spatially patterned calcium dynamics correlate with known differential growth rates between anterior and posterior compartments. Integrated calcium signaling activity decreases with increasing tissue size, and it responds to morphogenetic perturbations that impact organ growth. Together, these findings define how calcium signaling dynamics integrate upstream inputs to mediate multiple response outputs in developing epithelial organs.

Blocking of BDNF-TrkB signaling inhibits the promotion effect of neurological function recovery after treadmill training in rats with spinal cord injury.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the role of BDNF-TrkB signaling that promotes the recovery of neurological function in rats with incomplete spinal cord injury (SCI) after treadmill training (TT). SETTING: Rehabilitation Medicine Center of the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. METHODS: Forty rats were divided into five groups: (i) Sham; (ii) SCI and phosphate-buffered saline (PBS) (SCI/PBS); (iii) SCI-TT/PBS; (iv) SCI/TrkB-IgG; and (v) SCI-TT/TrkB-IgG. The intrathecal catheter and T10 contusion SCI model was established. At 7-day post SCI, the BDNF-TrkB signaling was blocked by TrkB-IgG. Exercise began at 8th day after SCI and continued for 4 weeks. The BBB scale and motor-evoked potential (MEP) were used for the evaluation of the locomotor functions. The BDNF/TrkB, PSD-95, SYP synthesis, and neuroprotective effect was determined by western blot, Nissl, or immunohistochemistry staining. RESULTS: The expression of BDNF and TrkB in the SCI-TT/PBS group was 1.46 ± 0.09 and 1.70 ± 0.22, respectively, higher than that in SCI/PBS group (0.51 ± 0.04 and 0.76 ± 0.07, respectively), relative to the Sham group. The BBB scores in the Sham, SCI/PBS, SCI-TT/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups were 21.00 ± 0.00, 7.63 ± 0.74, 12.13 ± 1.36, 7.88 ± 0.64, and 8.75 ± 0.88, respectively. The percentages of MEP responders/non-responders were 100, 0, 75, 0, and 50%. The MEP latencies in Sham, SCI-TT/PBS, and SCI-TT/TrkB-IgG groups were 6.65 ± 0.19, 13.32 ± 2.95, and 19.55 ± 4.55 ms, respectively. The number of NeuN+ neurons, the cell body area of motor neurons, PSD-95, and SYP expression in the SCI-TT/PBS group was significantly higher than that in the SCI/PBS, SCI/TrkB-IgG, and SCI-TT/TrkB-IgG groups. CONCLUSION: The BDNF-TrkB signaling is a critical pathway in exercise training that promotes the recovery of neurological function in rats with incomplete SCI.

Mechanistic Evaluation of the Protective Effect of Carnosine on Acute Lung Injury in Sepsis Rats.

This study analyzes the sepsis healing therapeutic potential of carnosine against experimentally sepsis-induced male albino rats. Carnosine in 2 different doses, 25 mg/kg and 50 mg/kg, were administered for 30 consecutive days. At the end of the treatment, lipid peroxidation, catalase, superoxide dismutase, glutathione peroxidase and myeloperoxidase activities were measured. Lungs weight and total protein content were determined in the bronchoalveolar fluid (BALF). Cytokines such as macrophage inhibitory factor (MIF), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) were determined in the BALF. In addition, the histopathological analysis was also carried out to understand the effect of carnosine in the cellular architecture. Carnosine treatment significantly renormalized the lipid peroxidation and other antioxidant enzymes. IL-ß, TNF-α, and MIF were found to be reduced after carnosine treatment. After carnosine treatment, the intensity of sepsis was significantly reduced evidenced by histopathological analysis. In western blot analysis, carnosine treatment causes the upregulation of IκBα together with the downregulation of the expressions of p65 and p-IKKα/ß (Ser 180/Ser 181).

Patterning of wound-induced intercellular Ca(2+) flashes in a developing epithelium.

Differential mechanical force distributions are increasingly recognized to provide important feedback into the control of an organ's final size and shape. As a second messenger that integrates and relays mechanical information to the cell, calcium ions (Ca(2+)) are a prime candidate for providing important information on both the overall mechanical state of the tissue and resulting behavior at the individual-cell level during development. Still, how the spatiotemporal properties of Ca(2+) transients reflect the underlying mechanical characteristics of tissues is still poorly understood. Here we use an established model system of an epithelial tissue, the Drosophila wing imaginal disc, to investigate how tissue properties impact the propagation of Ca(2+) transients induced by laser ablation. The resulting intercellular Ca(2+) flash is found to be mediated by inositol 1,4,5-trisphosphate and depends on gap junction communication. Further, we find that intercellular Ca(2+) transients show spatially non-uniform characteristics across the proximal-distal axis of the larval wing imaginal disc, which exhibit a gradient in cell size and anisotropy. A computational model of Ca(2+) transients is employed to identify the principle factors explaining the spatiotemporal patterning dynamics of intercellular Ca(2+) flashes. The relative Ca(2+) flash anisotropy is principally explained by local cell shape anisotropy. Further, Ca(2+) velocities are relatively uniform throughout the wing disc, irrespective of cell size or anisotropy. This can be explained by the opposing effects of cell diameter and cell elongation on intercellular Ca(2+) propagation. Thus, intercellular Ca(2+) transients follow lines of mechanical tension at velocities that are largely independent of tissue heterogeneity and reflect the mechanical state of the underlying tissue.

Effect of sling exercise combined with Schroth therapy on adolescents with mild idiopathic scoliosis: A twelve-week randomized controlled trial.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common structural deformity of the spine during adolescence, which could cause varying degrees of physical and mental damage to patients. Schroth therapy and sling exercise are widely used in the treatment of patients with AIS currently, and have shown the significant therapeutic effect relatively. OBJECTIVE: To observe the efficacy of sling exercise combined with Schroth therapy on adolescents with mild idiopathic scoliosis (MIS). METHODS: Sixty patients with AIS were randomly divided into the Schroth+sling group (n= 31) and the Schroth group (n= 29). Patients in both groups received Schroth therapy, and sling exercise was added in the Schroth+sling group. Before and after 12 weeks of treatment, the Cobb angle, angle of trunk rotation (ATR), Scoliosis Research Society-22 (SRS-22) scale score and averaged electromyography (AEMG) of bilateral paraspinal muscles were evaluated. RESULTS: After the treatment, Cobb angle, ATR in both groups were decreased compared with those before (P< 0.001), and the decrease in the Schroth+sling group was more obvious (P< 0.05). The AEMG of bilateral paraspinal muscles and the total score, posture, mental health of SRS-22 of the two groups improved compared with those before treatment (P< 0.05), and the Schroth+sling group had a significant improvement than the Schroth group (P< 0.05). CONCLUSION: Schroth therapy improved the degree of scoliosis, torticollis, quality of life, and bilateral paraspinal strength on adolescents with mild idiopathic scoliosis. The effect was more pronounced when the sling exercise was included in the treatment regimens.

Transcriptome profile analysis in spinal cord injury rats with transplantation of menstrual blood-derived stem cells.

Introduction: Menstrual blood-derived stem cells (MenSCs) are vital in treating many degenerative and traumatic disorders. However, the underlying molecular mechanisms remain obscure in MenSCs-treating spinal cord injury (SCI) rats. Methods: MenSCs were adopted into the injured sites of rat spinal cords at day 7 post surgery and the tissues were harvested for total RNA sequencing analysis at day 21 after surgery to investigate the expression patterns of RNAs. The differentially expressed genes (DEGs) were analyzed with volcano and heatmap plot. DEGs were sequentially analyzed by weighted gene co-expression network, functional enrichment, and competitive endogenous RNAs (ceRNA) network analysis. Next, expression of selected miRNAs, lncRNAs, circRNAs and mRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics packages and extra databases were enrolled to scoop the genes functions and their interaction relationships. Results: A total of 89 lncRNAs, 65 circRNAs, 120 miRNAs and 422 mRNAs were significantly upregulated and 65 lncRNAs, 72 circRNAs, 74 miRNAs, and 190 mRNAs were significantly downregulated in the MenSCs treated rats compared to SCI ones. Current investigation revealed that MenSCs treatment improve the recovery of the injured rats and the most significantly involved pathways in SCI regeneration were cell adhesion molecules, nature killer cell mediated cytotoxicity, primary immunodeficiency, chemokine signaling pathway, T cell receptor signaling pathway and B cell receptor signaling pathway. Moreover, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA ceRNA network of SCI was constructed. Finally, the protein-protein interaction (PPI) network was constructed using the top 100 DE mRNAs. The constructed PPI network included 47 nodes and 70 edges. Discussion: In summary, the above results revealed the expression profile and potential functions of differentially expressed (DE) RNAs in the injured spinal cords of rats in the MenSCs-treated and SCI groups, and this study may provide new clues to understand the mechanisms of MenSCs in treating SCI.

Efficacy and safety of vagus nerve stimulation on upper extremity motor function in patients with stroke: A meta-analysis of randomized controlled trials.

BACKGROUND: In 2021, the U.S. Food and Drug Administration (FDA) approved paired vagus nerve stimulation (VNS) for patients with moderate-to-severe upper extremity motor impairments following chronic ischemic stroke. OBJECTIVE: Previous meta-analyses have shown that VNS may impact stroke rehabilitation, but each has some limitations. METHODS: PubMed, Ovid, Cochrane Library, ScienceDirect, Web of Science and WHO ICTRP databases were searched until July 14, 2022 for randomized controlled trials (RCTs). We defined primary outcomes as Fugl-Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function Test (WMFT). Subgroup analyses included types of VNS, time since onset and long-term effects. Secondary outcomes included adverse events of VNS. RESULTS: Eight RCTs involving 266 patients were analyzed, of which five used direct VNS and three transcutaneous auricular VNS. The results revealed that VNS enhanced upper extremity function via FMA-UE (SMD = 0.73; 95% CI: 0.48 to 0.99; P < 0.00001) and WMFT (SMD = 0.82; 95% CI:0.52 to 1.13; P < 0.00001) in comparison to the control group, but showed no significant change on long-term effects of FMA-UE (SMD = 0.69; 95% CI: - 0.06 to 1.44; P = 0.07). There was no difference in adverse events between the VNS and control groups (RR = 1.16; 95% CI: 0.46 to 2.92; P = 0.74). CONCLUSION: For stroke victims with upper limb disabilities, VNS paired with rehabilitation was significantly safe and effective. More high-quality multicentric RCTs are needed to validate this conclusion.

A retrospective study of ultrasound-guided intervention for frozen shoulder in the frozen stage.

Background: To investigate the clinical value of ultrasound (US)-guided intervention for frozen shoulder (FS) in the frozen stage. Methods: This study included 40 patients who had primary FS in the frozen stage and were evaluated by US. These 40 patients have all received conservative treatment elsewhere, and no satisfactory results have been achieved, with no improvement in active and passive movement angles, and no improvement in scores within 3 months. Therefore, their previous treatment was set as comparison. All patients underwent US-guided shoulder joint capsule distension by injection of sterilized water. Of these participants, 22 patients with scapulohumeral periarthritis received a compound betamethasone injection, and 14 patients with thickened coracohumeral ligaments (CHLs) underwent acupotomy lysis, and the remaining 4 patients had no extra treatments. The Constant-Murley score (CMS) was evaluated before and after the operation and analysed for each patient. Results: Before treatment, the indices for the thickening of the subaxillary joint capsule, subacromial bursa (with or without effusion), long head of the biceps brachii tendon (LHBBT) and CHL were 40, 22, 16 and 14, respectively. After treatment, all the indices were significantly decreased (all P < 0.010) except for that of the LHBBT (P = 0.123). The patients' CMSs improved, with the median total CMS increasing from 59 points (interquartile range: 53-64 points) to 86 points (interquartile range: 78-90 points) (P < 0.010). While the internal rotation (Ir) of the shoulder joint did not improve (FDRs < 0.50), abduction, forward flexion (Ff) and external rotation (Er) improved significantly (all FDRs = 1.00). Conclusion: Compared with conservative treatment, US-guided intervention for FS in the frozen stage is highly effective and of great clinical value.

LncRNA/miRNA/mRNA ceRNA network analysis in spinal cord injury rat with physical exercise therapy.

Noncoding RNAs have been implicated in the pathophysiology of spinal cord injury (SCI), including cell death, glial scar formation, axonal collapse and demyelination, and inflammation. The evidence suggests that exercise therapy is just as effective as medical treatment in SCI. However, studies of competing endogenous RNA (ceRNA)-mediated regulation mechanisms in the therapy of SCI with exercise are rare. The focus of this research was to investigate the effect of exercise therapy on the expression levels of long noncoding RNA (lncRNA), microRNA (miRNA), and mRNA in rats with SCI. The RNA-seq technology has been used to examine the differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs), and genes (DEGs) between SCI and exercise therapy rats. The ceRNA network was established using interactions between miRNAs and mRNAs, as well as between miRNAs and lncRNAs/circRNAs. The Database for Annotation, Visualization, and Integrated Discovery was used to anticipate the underlying functions of mRNAs. Our current study identified 76 DELs, 33 DEMs, and 30 DEGs between groups of SCI rats and exercise therapy rats. Subsequently, these newly discovered ceRNA interaction axes could be important targets for the exercise treatment of SCI.

A decellularized spinal cord extracellular matrix-gel/GelMA hydrogel three-dimensional composite scaffold promotes recovery from spinal cord injury via synergism with human menstrual blood-derived stem cells.

Spinal cord injury (SCI), as a serious disabling disease, is still haunted by lacking of effective treatments. We previously found that transplantation of menstrual blood-derived mesenchymal stem cells (MenSCs) promoted axon regeneration in rats with SCI, while the abominable microenvironment after the SCI inhibited the survival of stem cells after transplantation. Biomaterials can support the activity of stem cells and accelerate the functional reconstruction of the injured spinal cord. In this study, we constructed a novel composite scaffold consisting of the decellularized spinal cord extracellular matrix-gel (DSCG) and the GelMA hydrogel, which harbored high water retention, wettability, degradability and soft mechanical property. In vitro, the DSCG/GelMA composite scaffold provided a dual bionic microenvironment with optimized bioactive components and favorable microstructures for the adhesion, proliferation and differentiation of MenSCs. After that, we prepared MenSC-encapsulated DSCG/GelMA composite scaffolds to bridge the 2 mm gap in rats with completely transected SCI. The in vivo results showed that the combined use of the DSCG/GelMA composite scaffold with MenSCs improved the motor function, reduced the inflammatory response, promoted neuronal differentiation, and inhibited the proliferation of reactive astrocytes after spinal cord injury. Altogether, our study provided a promising novel therapeutic option of using bioactive materials synergistic with stem cells for the treatment of SCI.

Impact of shoulder subluxation on peripheral nerve conduction and function of hemiplegic upper extremity in stroke patients: A retrospective, matched-pair study.

Purpose: To investigate the impact of shoulder subluxation (SS) on peripheral nerve conduction and function of the hemiplegic upper extremity (HUE) in poststroke patients.Methods: Thirty post-stroke patients were selected (SS group: 15 patients, non-SS group: 15 patients, respectively). Evaluation of nerve conduction in upper limbs: the compound muscle action potential (CMAP) amplitude and latency of suprascapular, axillary, musculocutaneous, radial, median, and ulnar nerves; the motor and sensory conduction velocity and the sensory nerve action potential (SNAP) amplitude of median, ulnar, and radial nerves. The Brunnstrom stage scale was used to evaluate the HUE motor function.Results: Compared with the healthy side, the CMAP and SNAP amplitudes of tested nerves on the HUE in both groups were lower, and the CMAP latency of the suprascapular, axillary and musculocutaneous nerves on the HUE in the SS group was longer (P < 0.05). Compared with the HUE in non-SS group, the CMAP amplitude of tested nerves (except ulnar) was decreased more (P < 0.05), the motor conduction velocity of the median nerve was lower (P < 0.05), and the Brunnstrom stage of the HUE was lower in SS group (P < 0.05).Conclusions: Stroke may lead to extensive abnormal nerve conduction on the HUE, and SS may aggravate the abnormality, which may disturb the recovery of upper limb function.

Tools to reverse-engineer multicellular systems: case studies using the fruit fly.

Reverse-engineering how complex multicellular systems develop and function is a grand challenge for systems bioengineers. This challenge has motivated the creation of a suite of bioengineering tools to develop increasingly quantitative descriptions of multicellular systems. Here, we survey a selection of these tools including microfluidic devices, imaging and computer vision techniques. We provide a selected overview of the emerging cross-talk between engineering methods and quantitative investigations within developmental biology. In particular, the review highlights selected recent examples from the Drosophila system, an excellent platform for understanding the interplay between genetics and biophysics. In sum, the integrative approaches that combine multiple advances in these fields are increasingly necessary to enable a deeper understanding of how to analyze both natural and synthetic multicellular systems.

A NEW REGISTRATION APPROACH FOR DYNAMIC ANALYSIS OF CALCIUM SIGNALS IN ORGANS.

Wing disc pouches of fruit flies are a powerful genetic model for studying physiological intercellular calcium (Ca 2+) signals for dynamic analysis of cell signaling in organ development and disease studies. A key to analyzing spatial-temporal patterns of Ca 2+ signal waves is to accurately align the pouches across image sequences. However, pouches in different image frames may exhibit extensive intensity oscillations due to Ca 2+ signaling dynamics, and commonly used multimodal non-rigid registration methods may fail to achieve satisfactory results. In this paper, we develop a new two-phase non-rigid registration approach to register pouches in image sequences. First, we conduct segmentation of the region of interest. (i.e., pouches) using a deep neural network model. Second, we use a B-spline based registration to obtain an optimal transformation and align pouches across the image sequences. Evaluated using both synthetic data and real pouch data, our method considerably outperforms the state-of-the-art non-rigid registration methods.

Human menstrual blood-derived stem cells promote functional recovery in a rat spinal cord hemisection model.

Spinal cord injury (SCI) is associated with a dismal prognosis including severe voluntary motor and sensory deficits in the presence of the current therapies, thus new and efficient treatment strategies are desperately required. Along with several advantages, such as easy accessibility, high-yield, potential of enormous proliferation, menstrual blood-derived mesenchymal stem cells (MenSCs) have been proposed as a promising strategy in regeneration medicine. In this study, the MenSCs were transplanted into incomplete thoracic (T10) spinal cord injury (SCI) rats, all rats were sacrificed at 7, 14, and 28 days after surgery. Based on the results, we found that MenSCs transplantation improved the hind limb motor function. Besides, H&E staining showed that MenSCs treatment markedly reduced cavity formation in the lesion site. Furthermore, treatment by MenSCs showed more MAP2-positive mature neurons, as well as axonal regeneration manifested by NF-200 and less expression of chondroitin sulfate proteoglycans (CSPGs) than the non-treatment in the lesion site. Additionally, immunofluorescence, Western blot, and qRT-PCR methods showed that levels of brain-derived neurotrophic factor (BDNF) were significantly higher in the injured spinal cord after implantation of MenSCs. Results of qRT-PCR indicated that inflammatory factors, including TNF-α and IL-1ß were inhibited after MenSCs transplantation. The improved motor function of hind limb and the increased cell body area of motor neurons were suppressed by blocking of the BDNF-TrkB signaling. It was eventually revealed that MenSCs implantation had beneficial therapeutic effects on the rehabilitation of the rat spinal cord hemisection model, mainly by enhancing the expression of BDNF. MenSCs transplantation may provide a novel therapeutic strategy for patients with SCI in the future.

HOXD-AS1 functions as an oncogenic ceRNA to promote NSCLC cell progression by sequestering miR-147a.

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide, and it occurs at a higher frequency in males. HOXD-AS1, an important cancer-associated long noncoding RNA (lncRNA), contributes to the development and progression of several cancers. However, the exact roles of HOXD-AS1 in NSCLC progression are still unknown. Here, we investigated the underlying mechanisms of HOXD-AS1 in human NSCLC tissues. We found that lncRNA HOXD-AS1 was specifically upregulated (P<0.001) in NSCLC tissues and promoted cancer cell growth by targeting miR-147a. Moreover, HOXD-AS1 expression positively correlated with NSCLC clinical pathologic characteristics (tumor size, P=0.006; tumor stage, P=0.044; recurrence, P=0.031) and survival rate (P=0.003). HOXD-AS1 knockdown reduced proliferation and promoted apoptosis of NSCLC cells. The dual-luciferase reporter assay showed that HOXD-AS1 could negatively regulate the expression of miR-147a. miR-147a inhibition abrogated the effect of HOXD-AS1 knockdown on the proliferation and apoptosis of NSCLC cells. Furthermore, HOXD-AS1 positively regulated the expression of pRB (a tumor suppressor protein) in NSCLC cells. Taken together, our data indicated that HOXD-AS1 might be an oncogenic lncRNA that promotes proliferation of NSCLC and could be a therapeutic target in NSCLC.

Neuromuscular interaction is required for neurotrophins-mediated locomotor recovery following treadmill training in rat spinal cord injury.

Recent results have shown that exercise training promotes the recovery of injured rat distal spinal cords, but are still unclear about the function of skeletal muscle in this process. Herein, rats with incomplete thoracic (T10) spinal cord injuries (SCI) with a dual spinal lesion model were subjected to four weeks of treadmill training and then were treated with complete spinal transection at T8. We found that treadmill training allowed the retention of hind limb motor function after incomplete SCI, even with a heavy load after complete spinal transection. Moreover, treadmill training alleviated the secondary injury in distal lumbar spinal motor neurons, and enhanced BDNF/TrkB expression in the lumbar spinal cord. To discover the influence of skeletal muscle contractile activity on motor function and gene expression, we adopted botulinum toxin A (BTX-A) to block the neuromuscular activity of the rat gastrocnemius muscle. BTX-A treatment inhibited the effects of treadmill training on motor function and BDNF/TrKB expression. These results indicated that treadmill training through the skeletal muscle-motor nerve-spinal cord retrograde pathway regulated neuralplasticity in the mammalian central nervous system, which induced the expression of related neurotrophins and promoted motor function recovery.