Effects of different mylohyoid muscle stimulations on swallowing cortex excitability in healthy subjects.

BACKGROUND: Dysphagia has been recognized by the World Health Organization as a medical disability. Improving mylohyoid muscle function plays an important role in pharyngeal dysphagia. The aim of this study was to evaluate the treatment of transcranial magnetic stimulation (TMS), peripheral magnetic stimulation (PMS), and electrical stimulation (ES) for dysphagia. METHODS: Forty healthy subjects were randomly divided into four groups: TMS+PMS, TMS, PMS, and ES. TMS stimulated the cortical representative area of the mylohyoid muscle and the PMS was directly stimulating the mylohyoid muscle, both of them at a frequency of 10 Hz for a total of 1,800 pulses. The intensity of ES was based on the subject's tolerance level, usually 2-5 mA. Functional near infrared spectroscopy (fNIRS) and motor evoked potential (MEP) of the mylohyoid muscle were used to evaluate the immediate effects of stimulation on swallowing cortex excitability of healthy subjects before and after intervention. RESULTS: The fNIRS results revealed notable activation across multiple channels in the four groups of healthy subjects both pre- and post- the intervention. Among these channels, the activation levels were most pronounced in the TMS+PMS group, followed by the TMS, PMS, and ES groups, respectively. Regarding the MEP results, post-intervention observations indicated a reduction in bilateral latency and an increase in bilateral amplitude in the TMS+PMS group. Additionally, the left amplitude exhibited an increase in the TMS group. CONCLUSIONS: In fNIRS, all four stimulation methods significantly activated the swallowing cortex of healthy subjects, and the activation of TMS+PMS was the most obvious, followed by TMS, PMS, and ES.

Calcitonin gene-related peptide: a potential protective agent in cerebral ischemia-reperfusion injury.

Ischemic stroke is the most common type of cerebrovascular disease with high disability and mortality rates, which severely burdens patients, their families, and society. At present, thrombolytic therapy is mainly used for the treatment of ischemic strokes. Even though it can achieve a good effect, thrombolytic recanalization can cause reperfusion injury. Calcitonin gene-related peptide (CGRP) is a neuropeptide that plays a neuroprotective role in the process of ischemia-reperfusion injury. By combining with its specific receptors, CGRP can induce vasodilation of local cerebral ischemia by directly activating the cAMP-PKA pathway in vascular smooth muscle cells and by indirectly activating the NO-cGMP pathway in an endothelial cell-dependent manner,thus rapidly increasing ischemic local blood flow together with reperfusion. CGRP, as a key effector molecule of neurogenic inflammation, can reduce the activation of microglia, downregulates Th1 classical inflammation, and reduce the production of TNF-α, IL-2, and IFN-γ and the innate immune response of macrophages, leading to the reduction of inflammatory factors. CGRP can reduce the overexpression of the aquaporin-4 (AQP-4) protein and its mRNA in the cerebral ischemic junction, and play a role in reducing cerebral edema. CGRP can protect endothelial cells from angiotensin II by reducing the production of oxidants and protecting antioxidant defense. Furthermore, CGRP-upregulated eNOS can further induce VEGF expression, which then promotes the survival and angiogenesis of vascular endothelial cells. CGRP can also reduce apoptosis by promoting the expression of Bcl-2 and inhibiting the expression of caspase-3. These effects suggest that CGRP can reduce brain injury and repair damaged nerve function. In this review, we focused on the role of CGRP in cerebral ischemia-reperfusion injury.

Research advances in the application of vagus nerve electrical stimulation in ischemic stroke.

Stroke seriously endangers human well-being and brings a severe burden to family and society. Different post-stroke dysfunctions result in an impaired ability to perform activities of daily living. Standard rehabilitative therapies may not meet the requirements for functional improvement after a stroke; thus, alternative approaches need to be proposed. Currently, vagus nerve stimulation (VNS) is clinically applied for the treatment of epilepsy, depression, cluster headache and migraine, while its treatment of various dysfunctions after an ischemic stroke is still in the clinical research stage. Recent studies have confirmed that VNS has neuroprotective effects in animal models of transient and permanent focal cerebral ischemia, and that its combination with rehabilitative training significantly improves upper limb motor dysfunction and dysphagia. In addition, vagus-related anatomical structures and neurotransmitters are closely implicated in memory-cognition enhancement processes, suggesting that VNS is promising as a potential treatment for cognitive dysfunction after an ischemic stroke. In this review, we outline the current status of the application of VNS (invasive and non-invasive) in diverse functional impairments after an ischemic stroke, followed by an in-depth discussion of the underlying mechanisms of its mediated neuroprotective effects. Finally, we summarize the current clinical implementation challenges and adverse events of VNS and put forward some suggestions for its future research direction. Research on VNS for ischemic stroke has reached a critical stage. Determining how to achieve the clinical transformation of this technology safely and effectively is important, and more animal and clinical studies are needed to clarify its therapeutic mechanism.

IL-37 As a Potential Biotherapeutics of Inflammatory Diseases.

Interleukin-37 (IL-37) was discovered as a new member of pro-inflammatory IL-1 superfamily. However, further studies suggested that IL-37 plays a critical anti-inflammatory role in innate and adaptive immunity. IL-37 may suppress the inflammatory process via intracellular SMAD family member 3 (SMAD3) and extracellular IL-18 Receptor alpha (IL-18Rα) signaling pathway, respectively. Meanwhile, the abnormal expression of IL-37 was observed in immune-mediated inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, atherosclerosis, systemic lupus erythematosus, asthma, and multiple sclerosis, which suggest IL-37 is a potential therapeutic target for these diseases. In this review, we summarize the anti-inflammatory mechanism of IL-37 and discuss the critical roles of IL-37 in the pathogenesis of these diseases. Further studies are required to confirm the effectiveness of IL-37 as a novel target for these inflammatory diseases.

Expression and Purification of Tag-removed Human IL37 by Digestion on Beads in Escherichia coli.

BACKGROUND: Human Interleukin 37 (IL37), a unique anti-inflammatory cytokine of IL1 family member, plays critical roles in innate and adaptive immunity and inflammation. OBJECTIVE: Preparation of high purity and tag-removed recombinant IL37 protein (rIL37) is critical for its clinical application. METHOD: In this study, we constructed an N-terminal cleavable GST-fused IL37 expression vector for recombinant expression. RESULTS: Subsequent to transformation and optimization of the induction temperature, the soluble expression level of rIL37 was 306.5 mg/L of culture medium at 18 °C induction in Escherichia coli. Meanwhile, rIL37 was digested on beads by GST-HRV3C protease during GST affinity chromatography. After further purification, the purity of rIL37 was higher than 99 %. Finally, the antiinflammatory activity of tag-removed protein was verified by the results showing that rIL37 suppressed IL1ß production in PBMCs. CONCLUSION: This work presents a protocol to produce high purity and tag-removed rIL37 with antiinflammatory activity, which provides the firm basis for advancing clinical application in human IL37-related inflammatory diseases.

A new enzyme-free quadratic SERS signal amplification approach for circulating microRNA detection in human serum.

In this communication, we proposed a new enzyme-free quadratic SERS signal amplification approach for the ultrasensitive detection of circulating miRNA in human serum. Combined with miRNA-triggered hybridization chain reaction and Ag(+)-mediated cascade amplification, a limit of miRNA detection as low as 0.3 fM could be achieved. More importantly, our method is suitable for the direct detection of circulating miRNAs in human serum collected from patients with different stages of chronic lymphocytic leukemia (CLL).

DNA-templated in situ growth of AgNPs on SWNTs: a new approach for highly sensitive SERS assay of microRNA.

In this communication, we find that the single-walled carbon nanotubes (SWNTs) can demonstrate an excellent ssDNA concentration-dependent surface enhanced Raman scattering (SERS) effect after the decoration of DNA-templated in situ grown AgNPs on the surface. Inspired by this, the SWNT@AgNPs hybrid nanocomposite was employed to achieve microRNA detection which is also sensitive to crude extraction from human breast cancer cells and even patient tissues before and after chemotherapy.

Silver nanoparticle gated, mesoporous silica coated gold nanorods (AuNR@MS@AgNPs): low premature release and multifunctional cancer theranostic platform.

Multifunctional nanoparticles integrated with an imaging module and therapeutic drugs are promising candidates for future cancer diagnosis and therapy. Mesoporous silica coated gold nanorods (AuNR@MS) have emerged as a novel multifunctional cancer theranostic platform combining the large specific surface area of mesoporous silica, which guarantees a high drug payload, and the photothermal modality of AuNRs. However, premature release and side effects of exogenous stimulus still hinder the further application of AuNR@MS. To address these issues, herein, we proposed a glutathione (GSH)-responsive multifunctional AuNR@MS nanocarrier with in situ formed silver nanoparticles (AgNPs) as the capping agent. The inner AuNR core functions as a hyperthermia agent, while the outer mesoporous silica shell exhibits the potential to allow a high drug payload, thus posing itself as an effective drug carrier. With the incorporation of targeting aptamers, the constructed nanocarriers show drug release in accordance with an intracellular GSH level with maximum drug release into tumors and minimum systemic release in the blood. Meanwhile, the photothermal effect of the AuNRs upon application to near-infrared (NIR) light led to a rapid rise in the local temperature, resulting in an enhanced cell cytotoxicity. Such a versatile theranostic system as AuNR@MS@AgNPs is expected to have a wide biomedical application and may be particularly useful for cancer therapy.

Universal surface-enhanced Raman scattering amplification detector for ultrasensitive detection of multiple target analytes.

Up to now, the successful fabrication of efficient hot-spot substrates for surface-enhanced Raman scattering (SERS) remains an unsolved problem. To address this issue, we describe herein a universal aptamer-based SERS biodetection approach that uses a single-stranded DNA as a universal trigger (UT) to induce SERS-active hot-spot formation, allowing, in turn, detection of a broad range of targets. More specifically, interaction between the aptamer probe and its target perturbs a triple-helix aptamer/UT structure in a manner that activates a hybridization chain reaction (HCR) among three short DNA building blocks that self-assemble into a long DNA polymer. The SERS-active hot-spots are formed by conjugating 4-aminobenzenethiol (4-ABT)-encoded gold nanoparticles with the DNA polymer through a specific Au-S bond. As proof-of-principle, we used this approach to quantify multiple target analytes, including thrombin, adenosine, and CEM cancer cells, achieving lowest limit of detection values of 18 pM, 1.5 nM, and 10 cells/mL, respectively. As a universal SERS detector, this prototype can be applied to many other target analytes through the use of suitable DNA-functional partners, thus inspiring new designs and applications of SERS for bioanalysis.