The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 ...The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or Medicine.Specifically,Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel,evaluating the structure of the Piezo channel and its physiological and pathological functions,and proposed a possible role for the Piezo channel in acupuncture mechanical stimulation.Professor Michael Xi Zhu introduced the discovery of the transient receptor potential(TRP)family,reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family,and that information regarding associations between the meridian and lymphatic systems may have important research and medical value.In addition,Professor Tianle Xu reviewed the history of ion channel research,particularly the physiological and pharmacological effects of non-classical ion channels(eg,the acid sensing ion channel family)and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture actions.Professor Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational research.Finally,Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical stimulation.Therefore,we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medicine is in helping interpret how acupuncture and moxibustion adjust homeostasis(ie,by activating mechanical and thermal sensation),which is conducive to validating and promoting the clinical efficacy of acupuncture modalities.展开更多
The development of secondary health complications following spinal cord injury has been increasingly recognized by healthcare professionals as a major concern.These problems most specifically affect complete or near-c...The development of secondary health complications following spinal cord injury has been increasingly recognized by healthcare professionals as a major concern.These problems most specifically affect complete or near-complete spinal cord injury patients(e.g.,those with minimal mobility),who are not typically rehabilitated with treadmill training approaches,because motor control and leg movements are largely impaired.However,recent pharmaceutical advances in central pattern generator activation may provide new therapeutic hopes for these spinal cord injury patients.This article provides a comprehensive overview,for the non-specialist,of the most recent advances in this field.展开更多
AIM: To determine the tissue and temporal distribution of human umbilical cord matrix stem (hUCMS) cells in severe combined immunodeficiency (SCID) mice. METHODS: For studying the localization of hUCMS cells, tritiate...AIM: To determine the tissue and temporal distribution of human umbilical cord matrix stem (hUCMS) cells in severe combined immunodeficiency (SCID) mice. METHODS: For studying the localization of hUCMS cells, tritiated thymidine-labeled hUCMS cells were injected in SCID mice and tissue distribution was quantitatively determined using a liquid scintillation counter at days 1, 3, 7 and 14. Furthermore, an immunofluorescence detection technique was employed in which anti-human mitochondrial antibody was used to identify hUCMS cells in mouse tissues. In order to visualize the distribution of transplanted hUCMS cells in H&E stained tissue sections, India Black ink 4415 was used to label the hUCMS cells. RESULTS: When tritiated thymidine-labeled hUCMS cells were injected systemically (iv) in female SCID mice, the lung was the major site of accumulation at 24 h after transplantation. With time, the cells migrated to other tissues, and on day three, the spleen, stomach, and small and large intestines were the major accumulation sites. On day seven, a relatively large amount of radioactivity was detected in the adrenal gland, uterus, spleen, lung, and digestive tract. In addition, labeled cells had crossed the blood brain barrier by day 1. CONCLUSION: These results indicate that peripherally injected hUCMS cells distribute quantitatively in a tissue-specific manner throughout the body.展开更多
Processing bioactive peptides from natural sources using electrodialysis with ultrafiltration membranes(EDUF)have gained attention since it can fractionate in terms of their charge and molecular weight.Quinoa is a pse...Processing bioactive peptides from natural sources using electrodialysis with ultrafiltration membranes(EDUF)have gained attention since it can fractionate in terms of their charge and molecular weight.Quinoa is a pseudo-cereal highlighted by its high protein content,amino acid profile and adapting growing conditions.The present work aimed at the production of quinoa peptides through fractionation using EDUF and to test the fractions according to antihypertensive and antidiabetic activity.Experimental data showed the production of peptides ranging between 0.4 and 1.5 k Da.Cationic(CQPF)(3.01%),anionic(AQPF)(1.18%)and the electrically neutral fraction quinoa protein hydrolysate(QPH)-EDUF(~95%)were obtained.In-vitro studies showed the highest glucose uptake modulation in L6 cell skeletal myoblasts in presence of QPH-EDUF and AQPF(17%and 11%)indicating potential antidiabetic activity.The antihypertensive effect studied in-vivo in spontaneously hypertensive rats(SHR),showed a decrease in systolic blood pressure in presence of the fractionated peptides,being 100 mg/kg a dose comparable to Captopril(positive control).These results contribute to the current knowledge of bioactive peptides from quinoa by reporting the relevance of EDUF as tool to produce selected peptide fractions.Nevertheless,further characterization is needed towards peptide sequencing,their respective role in the metabolism and scaling-up production using EDUF.展开更多
Background: There is evidence that sow heat stress(HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to midgesta...Background: There is evidence that sow heat stress(HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to midgestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi(LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control(CON, 20 ℃, n = 7 gilts, 18 LD samples) or controlled HS(cyclic 28 to 33 ℃, n = 8 gilts, 23 LD samples)conditions for 3 weeks.Results: A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles(false discovery rate(FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups(FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group(P = 0.004).Conclusions: These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular responses to gestational HS.展开更多
Gastrointestinal (GI) parasitic infections of sheep and goats were investigated in 69 farms located in Thessaly region of Greece, characterized by temperate Mediterranean climate, during two consecutive seasons. A tot...Gastrointestinal (GI) parasitic infections of sheep and goats were investigated in 69 farms located in Thessaly region of Greece, characterized by temperate Mediterranean climate, during two consecutive seasons. A total of 557 fecal samples were collected. Helminth eggs were detected in 44 (7.9%) samples. Strongyle-type eggs were found in 19 (3.4%) samples, Nematodirus spp. eggs in 6 (1.1%) samples, Trichuris spp. eggs in 16 (2.9%) samples, Fasciola hepatica in 3 (0.5%) samples, and Dicrocoelium dendriticum in 1 (0.2%) sample. Coccidian oocysts were found in 36 (6.5%) samples. Risk factors related to animal and farmer status, farm and pasture management, and environmental factors derived by satellite data were examined for their association with the prevalence of helmith infections. A logistic regression model showed that the educational level of farmers and the elevation of farm location were associated with helminth展开更多
To amplify the NS, NP, PB1, PB2 and PA internal genes of two equine H3N8 influenza A viruses isolated in Greece in 2003 and 2007 five primer pairs were designed. The derived sequences were analysed from a phylogenetic...To amplify the NS, NP, PB1, PB2 and PA internal genes of two equine H3N8 influenza A viruses isolated in Greece in 2003 and 2007 five primer pairs were designed. The derived sequences were analysed from a phylogenetic point of view and compared with the evolutionary patters of the HA and NA proteins. Comparison of nucleotide sequences of the five internal genes of the Greek strains showed high similarity (99.3% - 99.7%) to strains isolated from outbreaks in Europe and Asia during 2002-2008. A total of 11 amino acid substitutions of the surface protein NA and the RNP complex proteins were identified in the Greek strains compared to those of progenitor viruses circulating up to 2003. These substitutions were repeated in Chinese and Mongolian isolates from outbreaks in 2007-2008. Notably NS1 protein did not acquired amino acid substitutions and moreover, a stop codon introduced at position 220 was stably maintained in the Greek strains. Phylogenetic trees of the five internal genes did not show the same separation in clades. Greek strains classified them into the American sublineage (as for the PA) Florida clade II (as for the NP, NS1 and PB1) and among Chinese strains of 2007-2008 outbreaks (as for the PB2). Additionally, evolutionary profiles of these internal proteins, except PB2, indicated a parallel evolution fashion to the HA protein, suggesting the possible occurrence of genetic reassortment between H3N8 viruses of district evolutionary lineages. In conclusion, phylogenetic analysis of the internal genes reported in this study could establish a candidate framework for future scientific communications on the phylogenetic diversity and evolution of the equine influenza viruses.展开更多
Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits...Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.展开更多
Dear Editor,The common marmoset(Callithrix jacchus),a small New World monkey species,is considered an ideal non-human primate model for studying the evolution and neural mechanism of vocal behavior due to their rich c...Dear Editor,The common marmoset(Callithrix jacchus),a small New World monkey species,is considered an ideal non-human primate model for studying the evolution and neural mechanism of vocal behavior due to their rich call repertoire and vocal communication[1-3].Especially,the early vocal development of marmoset monkeys has attracted much attention,because newborn marmosets have been shown to exhibit a vocal development trajectory.Within two months after birth,marmosets'vocalizations undergo dramatic changes from cries to adult-like mature calls,a process that is influenced not only by inner physical maturation but also by parental care and feedback[4].展开更多
Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bi...Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bioactive form of ghrelin. However, recent advances indicate that both AG and UAG exert distinct and common effects in organisms. Soon after its discovery, ghrelin was shown to promote appetite and adiposity in animal and human models. In response to these anabolic effects, an impressive number of elements have suggested the influence of ghrelin on the regulation of metabolic functions and the development of obesityrelated disorders. However, due to the complexity ofits biochemical nature and the physiological processes it governs, some of the effects of ghrelin are still debated in the literature. Evidence suggests that ghrelin influences glucose homeostasis through the modulation of insulin secretion and insulin receptor signaling. On the other hand, insulin was also shown to influence circulating levels of ghrelin. Here, we review the relationship between ghrelin and insulin and we describe the impact of this interaction on the modulation of glucose homeostasis.展开更多
Chronic neuroinflammation is thought to play an etiological role in Alzheimer’s disease (AD) which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration...Chronic neuroinflammation is thought to play an etiological role in Alzheimer’s disease (AD) which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatio-temporal link between neuritic and amyloid pathology, with the obligatory enzyme for β-amyloid (Aβ) production, namely β-secretase-1 (BACE1), being overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aβ in these genetically modified animals. Further, it is unclear whether the inflammation seen in AD is the result of , or the cause of neuritic dystrophy. Here we explored the occurrence of AD-like axonal and dendritic pathology in adult rat brains affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated in the ipsilateral hippocampal lysates in the LPS-treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased β-amyloid precursor protein and Aβ antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.展开更多
AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experime...AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy donors.PBMCs were activated by lipopolysaccharide(LPS) stimulation before being treated with Adenosine triphosphate(ATP,1 mmol/L),human α-defensin-5(HD-5,50 μg/mL),and/or nigericin(Nig,30 μmol/L).For each experiment,the culture supernatants were collected separately from the cells.Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies.RESULTS:We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation.In the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely inhibited.Similarly,in the presence of HD-5,the release of IL-1β,but not the processing of IL-1β,was significantly inhibited from LPS-activated monocytes stimulated with Nig.Finally,we treated LPS-activated monocytes with ATP and Nig and collected the supernatants.We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes.Interestingly,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by HD-5.All images are representative of three independent experiments.CONCLUSION:These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.展开更多
Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity agai...Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vaccines (MLV). In this study, we explored the efficacy and immunological mechanisms of protection of MontanideTM Gel01 ST (Gel01) adjuvanted modified live PRRSV vaccine in pigs challenged with two genetically distinct strains of PRRSV. Gel01-MLV reduced lymph node pathology scores in pigs challenged with VR-2332 (parental strain of MLV vaccine) but not that in pigs challenged with MN184A (heterologous strain), when compared to that in pigs vaccinated with un-adjuvanted MLV. Pigs vaccinated with Gel01-MLV had higher levels of PRRS-specific antibodies, as measured by IDEXX ELISA and virus neutralizing antibodies, after vaccination and VR-2332 challenge. In addition, pigs vaccinated with Gel01-MLV had decreased levels of IFN-γ, IL-10, and T-regulatory lymphocytes in the blood as compared to that in pigs vaccinated with MLV alone. Interestingly, we found that addition of Gel01 did not change the profile of other T lymphocyte populations after PRRSV challenge. These results demonstrate that the MLV adjuvanted with Gel01 provides enhanced protection against homologous PRRSV infection, possibly by regulating the production of PRRSV-specific antibodies and cytokines involved in the development of T-regulatory cells. Thus, Gel01 ST is a promising adjuvant that can be formulated with PRRSV MLV vaccines to reduce disease severity and tissue damage caused by PRRSV infection in pigs.展开更多
Objective · Formalin is a classic and most widely used algogenic substance, but its itchy effect is not clear. The present study aims to explore the hypothesis that formalin may induce itch as well as pain. Metho...Objective · Formalin is a classic and most widely used algogenic substance, but its itchy effect is not clear. The present study aims to explore the hypothesis that formalin may induce itch as well as pain. Methods · Flinching, as well as licking and forelimb wiping of the site of injection were counted as pain responses, whereas biting and hind paw scratching of the cheek were counted as itchy responses. To discriminate formalin-induced sensations in rats, the irritant(saline as control) was injected, and then pain and itchy responses were recorded.Results · Intraplantar injection of formalin elicited biphasic behavior responses characterized as flinching, as well as biting or licking of the hind paw without significant gender differences. Following intradermal administration of formalin to the cheek, rats exhibited episodic forelimb wiping of the cheek, representative of pain. No gender difference was noticed for this type of behavior. In addition, episodes of hind paw scratches of the cheek, representative of pruritoceptive responses, also occurred. Interestingly, hind paw scratches appeared to be more pronounced in male than in female rats. Conclusion · Intradermal administration of formalin elicits pruritoceptive as well as nociceptive responses in rats.展开更多
Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent decades.The field of psychiatry is constantly challenged...Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent decades.The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations,and that has to be supported by a continuous growth in knowledge.The majority of neuropsychiatric symptoms reflect complex geneenvironment interactions,with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms.It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stressrelated behavioural phenotypes in both paternal and maternal lineages,providing further supporting evidence for heritability in humans.However,unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions.While rodents will remain the dominant model system for preclinical studies(especially for addressing complex behavioural phenotypes),there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models.Here,we will discuss the utility and advantages of two alternative model organisms–Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.展开更多
Knot theory is a branch of topology in pure mathematics, however, it has been increasingly used in different sciences such as chemistry. Mathematically, a knot is a subset of three-dimensional space which is homeomorp...Knot theory is a branch of topology in pure mathematics, however, it has been increasingly used in different sciences such as chemistry. Mathematically, a knot is a subset of three-dimensional space which is homeomorphic to a circle and it is only defined in a closed loop. In chemistry, knots have been applied to synthetic molecular design. Mathematics and chemistry together can work to determine, characterize and create knots which help to understand different molecular designs and then forecast their physical features. In this study, we provide an introduction to the knot theory and its topological concepts, and then we extend it to the context of chemistry. We present parametric representations for several synthetic knots. The main goal of this paper is to develop a geometric and topological intuition for molecular knots using parametric equations. Since parameterizations are non-unique;there is more than one set of parametric equations to specify the same molecular knots. This parametric representation can be used easily to express geometrically molecular knots and would be helpful to find out more complicated molecular models.展开更多
The purpose of the study was to analyse on pain following traumatic spinal cord injury, its prevalence, the types of pain present, the common treatments used and their perceived effectiveness in the management of thes...The purpose of the study was to analyse on pain following traumatic spinal cord injury, its prevalence, the types of pain present, the common treatments used and their perceived effectiveness in the management of these reported pain types. A cross sectional study was carried out at St Giles Rehabilitation Centre and from members of the Spinal Injuries Association of Zimbabwe (SIAZ). A researcher-administered questionnaire was used to collect data from 24 participants with traumatic spinal cord injury. The questionnaire elicited information on demographic data, pain characteristics and the perceived effectiveness of the common treatments used. Among the 24 participants in the study, 17 were males (70.8%) and 7 were females (29.2%). Pain prevalence was 79.2% among the study participants and approximately a fifth (21.03%) of all participants rated their pain as severe. Eight (33.3%) of the participants had neuropathic pain while 11 (45.8%) had both nociceptive and neuropathic pain types. However, no association was found between sex, age, time post injury when tested against the presence of pain (p > 0.05). Weather changes aggravated almost every type of pain reported. Both pharmacological and non-pharmacological methods were used to manage the pain but their perceived effectiveness was rated as low. The majority of the traumatic spinal cord injured people experienced some pain and this pain was severe in a fifth of all participants. Pain significantly affected their quality of life. Physiotherapists and other medical professionals need to be aware of this and should employ pain reducing modalities and empathy when dealing with these patients.展开更多
Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase(MAPK)pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Se...Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase(MAPK)pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury,but there has been little research focusing on the hypoglossal nerve injury and repair.In this study,we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days.p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury;exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus.Under transmission electron microscopy,we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury.Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.展开更多
The peripheral nervous system(PNS)is essential for performing and maintaining various motor and sensory functions.Abnormalities can lead to a series of peripheral neurological conditions,such as paraesthesia,pain,or s...The peripheral nervous system(PNS)is essential for performing and maintaining various motor and sensory functions.Abnormalities can lead to a series of peripheral neurological conditions,such as paraesthesia,pain,or spasms,which are debilitating and lowering the quality of life.Thecurrent guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction,which occur already at an advancedstage.There are currently no effective methods that visually reflect the extent of peripheral neuropathy.In our study,we present a novel in vivoand in situ real-time imaging of peripheral nerves based on the second near-infrared window(NIR-II)fluoresce nee.In NIR-II system,lead sulfidequa ntum dots(PbS Qds)with NIR-II fluoresce nee specifically bound to motor neuro rvspecific protein agrin,acting as image con trast.In micemodel,peripheral nerves were visible as soon as after 2 h post injection.We provide evidenee for the efficacy of this approach,which allows todirectly dem on strate peripheral nerves,their structure,and pote ntial damagesites and degree.Furthermore,our products were of goodbiocompatibility,while the n eural fluoresce nee signal was solid,bright and stable for 4 h in vivo.Thus,overall,our results suggest that NIR-II isan effective new method for direct imaging of peripheral nerves in vivo,opening new horizons on early,improved and more precise,targeteddiag no sis.A resulti ng more rapid installatio n of perso nalized therapy facilitates a better prognosis of clinical peripheral neuropathy.展开更多
基金the National Natural Science Foundation of China(Nos.82030125 and 81873369)。
文摘The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or Medicine.Specifically,Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel,evaluating the structure of the Piezo channel and its physiological and pathological functions,and proposed a possible role for the Piezo channel in acupuncture mechanical stimulation.Professor Michael Xi Zhu introduced the discovery of the transient receptor potential(TRP)family,reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family,and that information regarding associations between the meridian and lymphatic systems may have important research and medical value.In addition,Professor Tianle Xu reviewed the history of ion channel research,particularly the physiological and pharmacological effects of non-classical ion channels(eg,the acid sensing ion channel family)and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture actions.Professor Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational research.Finally,Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical stimulation.Therefore,we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medicine is in helping interpret how acupuncture and moxibustion adjust homeostasis(ie,by activating mechanical and thermal sensation),which is conducive to validating and promoting the clinical efficacy of acupuncture modalities.
文摘The development of secondary health complications following spinal cord injury has been increasingly recognized by healthcare professionals as a major concern.These problems most specifically affect complete or near-complete spinal cord injury patients(e.g.,those with minimal mobility),who are not typically rehabilitated with treadmill training approaches,because motor control and leg movements are largely impaired.However,recent pharmaceutical advances in central pattern generator activation may provide new therapeutic hopes for these spinal cord injury patients.This article provides a comprehensive overview,for the non-specialist,of the most recent advances in this field.
基金Supported by (in part) the Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Researchthe KSU College of Veterinary Medicine Dean's FundKSU Targeted Excellence, Kansas State Legislative Appropriation and NIH1R21CA135599
文摘AIM: To determine the tissue and temporal distribution of human umbilical cord matrix stem (hUCMS) cells in severe combined immunodeficiency (SCID) mice. METHODS: For studying the localization of hUCMS cells, tritiated thymidine-labeled hUCMS cells were injected in SCID mice and tissue distribution was quantitatively determined using a liquid scintillation counter at days 1, 3, 7 and 14. Furthermore, an immunofluorescence detection technique was employed in which anti-human mitochondrial antibody was used to identify hUCMS cells in mouse tissues. In order to visualize the distribution of transplanted hUCMS cells in H&E stained tissue sections, India Black ink 4415 was used to label the hUCMS cells. RESULTS: When tritiated thymidine-labeled hUCMS cells were injected systemically (iv) in female SCID mice, the lung was the major site of accumulation at 24 h after transplantation. With time, the cells migrated to other tissues, and on day three, the spleen, stomach, and small and large intestines were the major accumulation sites. On day seven, a relatively large amount of radioactivity was detected in the adrenal gland, uterus, spleen, lung, and digestive tract. In addition, labeled cells had crossed the blood brain barrier by day 1. CONCLUSION: These results indicate that peripherally injected hUCMS cells distribute quantitatively in a tissue-specific manner throughout the body.
基金financially supported by the Postdoctoral Fellowship N°3190683 of Dr.Adrián González-Munoz from the Chilean Agencia Nacional de Investigación y Desarrollo(ANID)the Natural Sciences and Engineering Research Council of Canada(NSERC)Discovery Grant Program(Grant SD RGPIN-2018-04128 of Prof.Laurent Bazinet)。
文摘Processing bioactive peptides from natural sources using electrodialysis with ultrafiltration membranes(EDUF)have gained attention since it can fractionate in terms of their charge and molecular weight.Quinoa is a pseudo-cereal highlighted by its high protein content,amino acid profile and adapting growing conditions.The present work aimed at the production of quinoa peptides through fractionation using EDUF and to test the fractions according to antihypertensive and antidiabetic activity.Experimental data showed the production of peptides ranging between 0.4 and 1.5 k Da.Cationic(CQPF)(3.01%),anionic(AQPF)(1.18%)and the electrically neutral fraction quinoa protein hydrolysate(QPH)-EDUF(~95%)were obtained.In-vitro studies showed the highest glucose uptake modulation in L6 cell skeletal myoblasts in presence of QPH-EDUF and AQPF(17%and 11%)indicating potential antidiabetic activity.The antihypertensive effect studied in-vivo in spontaneously hypertensive rats(SHR),showed a decrease in systolic blood pressure in presence of the fractionated peptides,being 100 mg/kg a dose comparable to Captopril(positive control).These results contribute to the current knowledge of bioactive peptides from quinoa by reporting the relevance of EDUF as tool to produce selected peptide fractions.Nevertheless,further characterization is needed towards peptide sequencing,their respective role in the metabolism and scaling-up production using EDUF.
基金partially funded by Australian Pork Limited (APL2017/2216)the Postgraduate Research Scholarship and the Melbourne Research Scholarship from APL and The University of Melbourne,respectively
文摘Background: There is evidence that sow heat stress(HS) during gestation affects fetal development with implications for impaired muscle growth. We have previously demonstrated that maternal HS during early to midgestation compromised muscle fibre hyperplasia in developing fetal pigs. Thus, we hypothesised these phenotypic changes are associated with a change in expression of genes regulating fetal skeletal muscle development and metabolism. To test this, at d 60 of gestation, RNA sequencing and immunohistochemistry were performed on fetal longissimus dorsi(LD) muscle biopsies collected from pregnant gilts that had experienced either thermoneutral control(CON, 20 ℃, n = 7 gilts, 18 LD samples) or controlled HS(cyclic 28 to 33 ℃, n = 8 gilts, 23 LD samples)conditions for 3 weeks.Results: A total of 282 genes were differentially expressed between the HS and CON groups in female LD muscles(false discovery rate(FDR) ≤ 0.05), whereas no differentially expressed genes were detected in male LD muscles between the two groups(FDR > 0.05). Gestational HS increased the expression of genes associated with transcription corepressor activity, adipogenesis cascades, negative regulation of angiogenesis and pro-inflammatory signalling in female LD muscles. Immunohistochemical analyses revealed a decreased muscle vascularity density in fetuses from HS group for both sexes compared to those from the CON group(P = 0.004).Conclusions: These results reveal gilt HS during early to mid-gestation altered gene expression profiles in fetal LD muscles in a sexually dimorphic manner. The molecular responses, including transcription and angiogenesis repressions and enhanced adipogenesis cascades, were exclusively observed in females. However, the associated reductions in muscle vascularity were observed independently of sexes. Collectively this may indicate female fetal pigs are more adaptive to gestational HS in terms of gene expression changes, and/or there may be sexually dimorphic differences with respect to the timing of muscle molecular responses to gestational HS.
文摘Gastrointestinal (GI) parasitic infections of sheep and goats were investigated in 69 farms located in Thessaly region of Greece, characterized by temperate Mediterranean climate, during two consecutive seasons. A total of 557 fecal samples were collected. Helminth eggs were detected in 44 (7.9%) samples. Strongyle-type eggs were found in 19 (3.4%) samples, Nematodirus spp. eggs in 6 (1.1%) samples, Trichuris spp. eggs in 16 (2.9%) samples, Fasciola hepatica in 3 (0.5%) samples, and Dicrocoelium dendriticum in 1 (0.2%) sample. Coccidian oocysts were found in 36 (6.5%) samples. Risk factors related to animal and farmer status, farm and pasture management, and environmental factors derived by satellite data were examined for their association with the prevalence of helmith infections. A logistic regression model showed that the educational level of farmers and the elevation of farm location were associated with helminth
文摘To amplify the NS, NP, PB1, PB2 and PA internal genes of two equine H3N8 influenza A viruses isolated in Greece in 2003 and 2007 five primer pairs were designed. The derived sequences were analysed from a phylogenetic point of view and compared with the evolutionary patters of the HA and NA proteins. Comparison of nucleotide sequences of the five internal genes of the Greek strains showed high similarity (99.3% - 99.7%) to strains isolated from outbreaks in Europe and Asia during 2002-2008. A total of 11 amino acid substitutions of the surface protein NA and the RNP complex proteins were identified in the Greek strains compared to those of progenitor viruses circulating up to 2003. These substitutions were repeated in Chinese and Mongolian isolates from outbreaks in 2007-2008. Notably NS1 protein did not acquired amino acid substitutions and moreover, a stop codon introduced at position 220 was stably maintained in the Greek strains. Phylogenetic trees of the five internal genes did not show the same separation in clades. Greek strains classified them into the American sublineage (as for the PA) Florida clade II (as for the NP, NS1 and PB1) and among Chinese strains of 2007-2008 outbreaks (as for the PB2). Additionally, evolutionary profiles of these internal proteins, except PB2, indicated a parallel evolution fashion to the HA protein, suggesting the possible occurrence of genetic reassortment between H3N8 viruses of district evolutionary lineages. In conclusion, phylogenetic analysis of the internal genes reported in this study could establish a candidate framework for future scientific communications on the phylogenetic diversity and evolution of the equine influenza viruses.
文摘Biodegradable Nanoparticles (NPs) are under intense investigation due to their potential application in targeted drug delivery. Upon their entry to the biological system, they encounter the immune system, which limits their availability at the intended site. Most importantly, the innate immune system is the one that acts as the first line of defense against foreign materials. It can be activated by collectin proteins which recognize the structural pattern of polysaccharide on the surface of microorganisms. NPs may interact with these proteins in a similar way, and the interaction may lead to beneficial outcomes in vaccine delivery. On the other hand, in targeted drug delivery, it is desirable for the NPs not to be recognized as foreign material as this may lead to their fast elimination from the system through mechanism such as opsonization. We investigated the interaction of PEGylated and un-PEGylated PLGA NPs with Recombinant Human Mannose-Binding Protein (HMBP) in an effort to understand the effect of surface modification on their binding to the protein. Results show that both PLGA-COOH and PLGA-PEG-NH2 bind to HMBP as studied using dynamic light scattering (DLS), fluoresce and UV-vis spectroscopy. However, their binding is shown to have different effect on the structure of the protein. Study done using fluorescence spectroscopy displayed a decrease in fluorescence emission of the protein upon binding to PLGA-COOH. On the other hand the fluorescence emission of the protein increased upon binding to the PLGA-PEG-NH2 indicating conformational changes in the protein structure.
基金supported by the STI2030-Major Projects(2021ZD0203900)Shanghai Municipal Science and Technology(22ZR1481500)+1 种基金"Strategic Priority Research Program"of the Chinese Academy of Sciences(XDB32010000)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05).
文摘Dear Editor,The common marmoset(Callithrix jacchus),a small New World monkey species,is considered an ideal non-human primate model for studying the evolution and neural mechanism of vocal behavior due to their rich call repertoire and vocal communication[1-3].Especially,the early vocal development of marmoset monkeys has attracted much attention,because newborn marmosets have been shown to exhibit a vocal development trajectory.Within two months after birth,marmosets'vocalizations undergo dramatic changes from cries to adult-like mature calls,a process that is influenced not only by inner physical maturation but also by parental care and feedback[4].
基金Supported by Fonds de Recherche du Québec en Santé(toLaplante M and St-Pierre DH)Operating grants from NaturalSciences and Engineering Research Council of Canada and Diabète QuébecLaplante M also holds operating grants from the Canadian Institutes of Health Research,Canadian Liver Foundation and the Fondation de l’Institut Universitaire de Cardiologieet de Pneumologie de Québec
文摘Ghrelin is a 28 amino acid peptide mainly derived from the oxyntic gland of the stomach. Both acylated(AG) and unacylated(UAG) forms of ghrelin are found in the circulation. Initially, AG was considered as the only bioactive form of ghrelin. However, recent advances indicate that both AG and UAG exert distinct and common effects in organisms. Soon after its discovery, ghrelin was shown to promote appetite and adiposity in animal and human models. In response to these anabolic effects, an impressive number of elements have suggested the influence of ghrelin on the regulation of metabolic functions and the development of obesityrelated disorders. However, due to the complexity ofits biochemical nature and the physiological processes it governs, some of the effects of ghrelin are still debated in the literature. Evidence suggests that ghrelin influences glucose homeostasis through the modulation of insulin secretion and insulin receptor signaling. On the other hand, insulin was also shown to influence circulating levels of ghrelin. Here, we review the relationship between ghrelin and insulin and we describe the impact of this interaction on the modulation of glucose homeostasis.
文摘Chronic neuroinflammation is thought to play an etiological role in Alzheimer’s disease (AD) which is characterized pathologically by amyloid and tau formation, as well as neuritic dystrophy and synaptic degeneration. The causal relationship between these pathological events is a topic of ongoing research and discussion. Recent data from transgenic AD models point to a tight spatio-temporal link between neuritic and amyloid pathology, with the obligatory enzyme for β-amyloid (Aβ) production, namely β-secretase-1 (BACE1), being overexpressed in axon terminals undergoing dystrophic change. However, the axonal pathology inherent with BACE1 elevation seen in transgenic AD mice may be secondary to increased soluble Aβ in these genetically modified animals. Further, it is unclear whether the inflammation seen in AD is the result of , or the cause of neuritic dystrophy. Here we explored the occurrence of AD-like axonal and dendritic pathology in adult rat brains affected by LPS-induced chronic neuroinflammation. Unilateral intracerebral LPS injection induced prominent inflammatory response in glial cells in the ipsilateral cortex and hippocampal formation. BACE1 protein levels were elevated in the ipsilateral hippocampal lysates in the LPS-treated animals relative to controls. BACE1 immunoreactive dystrophic axons appeared in the LPS-treated ipsilateral cortex and hippocampal formation, colocalizing with increased β-amyloid precursor protein and Aβ antibody (4G8) immunolabeling. Quantitative Golgi studies revealed reduction of dendritic branching points and spine density on cortical layer III and hippocampal CA3 pyramidal neurons in the LPS-treated ipsilateral cerebrum. These findings suggest that Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration occur in wildtype mammalian brain in partnership with neuroinflammation following LPS injection.
基金Supported by NIH R21 AI085416 (to Shi J)NIH NCRR P20-RR017686 (to PI:Daniel MarcusShi J)
文摘AIM:To investigate whether caspase-1 activation/intracellular processing of pro-interleukin-1β(pro-IL-1β) and extracellular release of mature IL-1β from activated monocytes are separable events.METHODS:All experiments were performed on fresh or overnight cultured human peripheral blood monocytes(PBMCs) that were isolated from healthy donors.PBMCs were activated by lipopolysaccharide(LPS) stimulation before being treated with Adenosine triphosphate(ATP,1 mmol/L),human α-defensin-5(HD-5,50 μg/mL),and/or nigericin(Nig,30 μmol/L).For each experiment,the culture supernatants were collected separately from the cells.Cell lysates and supernatants were both subject to immunoprecipitation with anti-IL1β antibodies followed by western blot analysis with anti-caspase-1 and anti-IL-1β antibodies.RESULTS:We found that pro-IL-1β was processed to mature IL-1β in LPS-activated fresh and overnight cultured human monocytes in response to ATP stimulation.In the presence of HD-5,this release of IL-1β,but not the processing of pro-IL-1β to IL-1β,was completely inhibited.Similarly,in the presence of HD-5,the release of IL-1β,but not the processing of IL-1β,was significantly inhibited from LPS-activated monocytes stimulated with Nig.Finally,we treated LPS-activated monocytes with ATP and Nig and collected the supernatants.We found that both ATP and Nig stimulation could activate and release cleaved caspase-1 from the monocytes.Interestingly,and contrary to IL-1β processing and release,caspase-1 cleavage and release was not blocked by HD-5.All images are representative of three independent experiments.CONCLUSION:These data suggest that caspase-1 activation/processing of pro-IL-1β by caspase-1 and the release of mature IL-1β from human monocytes are distinct and separable events.
文摘Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease caused by the PRRS virus. The MontanideTM class of flexible polymeric adjuvants has recently been shown to enhance protective immunity against PRRSV infection in piglets when used in combination with PRRS modified live vaccines (MLV). In this study, we explored the efficacy and immunological mechanisms of protection of MontanideTM Gel01 ST (Gel01) adjuvanted modified live PRRSV vaccine in pigs challenged with two genetically distinct strains of PRRSV. Gel01-MLV reduced lymph node pathology scores in pigs challenged with VR-2332 (parental strain of MLV vaccine) but not that in pigs challenged with MN184A (heterologous strain), when compared to that in pigs vaccinated with un-adjuvanted MLV. Pigs vaccinated with Gel01-MLV had higher levels of PRRS-specific antibodies, as measured by IDEXX ELISA and virus neutralizing antibodies, after vaccination and VR-2332 challenge. In addition, pigs vaccinated with Gel01-MLV had decreased levels of IFN-γ, IL-10, and T-regulatory lymphocytes in the blood as compared to that in pigs vaccinated with MLV alone. Interestingly, we found that addition of Gel01 did not change the profile of other T lymphocyte populations after PRRSV challenge. These results demonstrate that the MLV adjuvanted with Gel01 provides enhanced protection against homologous PRRSV infection, possibly by regulating the production of PRRSV-specific antibodies and cytokines involved in the development of T-regulatory cells. Thus, Gel01 ST is a promising adjuvant that can be formulated with PRRSV MLV vaccines to reduce disease severity and tissue damage caused by PRRSV infection in pigs.
文摘Objective · Formalin is a classic and most widely used algogenic substance, but its itchy effect is not clear. The present study aims to explore the hypothesis that formalin may induce itch as well as pain. Methods · Flinching, as well as licking and forelimb wiping of the site of injection were counted as pain responses, whereas biting and hind paw scratching of the cheek were counted as itchy responses. To discriminate formalin-induced sensations in rats, the irritant(saline as control) was injected, and then pain and itchy responses were recorded.Results · Intraplantar injection of formalin elicited biphasic behavior responses characterized as flinching, as well as biting or licking of the hind paw without significant gender differences. Following intradermal administration of formalin to the cheek, rats exhibited episodic forelimb wiping of the cheek, representative of pain. No gender difference was noticed for this type of behavior. In addition, episodes of hind paw scratches of the cheek, representative of pruritoceptive responses, also occurred. Interestingly, hind paw scratches appeared to be more pronounced in male than in female rats. Conclusion · Intradermal administration of formalin elicits pruritoceptive as well as nociceptive responses in rats.
文摘Mental illness remains the greatest chronic health burden globally with few inroads having been made despite significant advances in genomic knowledge in recent decades.The field of psychiatry is constantly challenged to bring new approaches and tools to address and treat the needs of vulnerable individuals and subpopulations,and that has to be supported by a continuous growth in knowledge.The majority of neuropsychiatric symptoms reflect complex geneenvironment interactions,with epigenetics bridging the gap between genetic susceptibility and environmental stressors that trigger disease onset and drive the advancement of symptoms.It has more recently been demonstrated in preclinical models that epigenetics underpins the transgenerational inheritance of stressrelated behavioural phenotypes in both paternal and maternal lineages,providing further supporting evidence for heritability in humans.However,unbiased prospective studies of this nature are practically impossible to conduct in humans so preclinical models remain our best option for researching the molecular pathophysiologies underlying many neuropsychiatric conditions.While rodents will remain the dominant model system for preclinical studies(especially for addressing complex behavioural phenotypes),there is scope to expand current research of the molecular and epigenetic pathologies by using invertebrate models.Here,we will discuss the utility and advantages of two alternative model organisms–Caenorhabditis elegans and Drosophila melanogaster-and summarise the compelling insights of the epigenetic regulation of transgenerational inheritance that are potentially relevant to human psychiatry.
文摘Knot theory is a branch of topology in pure mathematics, however, it has been increasingly used in different sciences such as chemistry. Mathematically, a knot is a subset of three-dimensional space which is homeomorphic to a circle and it is only defined in a closed loop. In chemistry, knots have been applied to synthetic molecular design. Mathematics and chemistry together can work to determine, characterize and create knots which help to understand different molecular designs and then forecast their physical features. In this study, we provide an introduction to the knot theory and its topological concepts, and then we extend it to the context of chemistry. We present parametric representations for several synthetic knots. The main goal of this paper is to develop a geometric and topological intuition for molecular knots using parametric equations. Since parameterizations are non-unique;there is more than one set of parametric equations to specify the same molecular knots. This parametric representation can be used easily to express geometrically molecular knots and would be helpful to find out more complicated molecular models.
文摘The purpose of the study was to analyse on pain following traumatic spinal cord injury, its prevalence, the types of pain present, the common treatments used and their perceived effectiveness in the management of these reported pain types. A cross sectional study was carried out at St Giles Rehabilitation Centre and from members of the Spinal Injuries Association of Zimbabwe (SIAZ). A researcher-administered questionnaire was used to collect data from 24 participants with traumatic spinal cord injury. The questionnaire elicited information on demographic data, pain characteristics and the perceived effectiveness of the common treatments used. Among the 24 participants in the study, 17 were males (70.8%) and 7 were females (29.2%). Pain prevalence was 79.2% among the study participants and approximately a fifth (21.03%) of all participants rated their pain as severe. Eight (33.3%) of the participants had neuropathic pain while 11 (45.8%) had both nociceptive and neuropathic pain types. However, no association was found between sex, age, time post injury when tested against the presence of pain (p > 0.05). Weather changes aggravated almost every type of pain reported. Both pharmacological and non-pharmacological methods were used to manage the pain but their perceived effectiveness was rated as low. The majority of the traumatic spinal cord injured people experienced some pain and this pain was severe in a fifth of all participants. Pain significantly affected their quality of life. Physiotherapists and other medical professionals need to be aware of this and should employ pain reducing modalities and empathy when dealing with these patients.
文摘Studies have shown that sensory nerve damage can activate the p38 mitogen-activated protein kinase(MAPK)pathway,but whether the same type of nerve injury after exercise activates the p38MAPK pathway remains unclear.Several studies have demonstrated that nerve growth factor may play a role in the repair process after peripheral nerve injury,but there has been little research focusing on the hypoglossal nerve injury and repair.In this study,we designed and established rat models of hypoglossal nerve crush injury and gave intraperitoneal injections of exogenous nerve growth factor to rats for 14 days.p38MAPK activity in the damaged neurons was increased following hypoglossal nerve crush injury;exogenous nerve growth factor inhibited this increase in acitivity and increased the survival rate of motor neurons within the hypoglossal nucleus.Under transmission electron microscopy,we found that the injection of nerve growth factor contributed to the restoration of the morphology of hypoglossal nerve after crush injury.Our experimental findings indicate that exogenous nerve growth factor can protect damaged neurons and promote hypoglossal nerve regeneration following hypoglossal nerve crush injury.
基金This work was supported by National Natural Science Foundation of China(Nos.81672247,81772339,8181101445,81811530750,and 81811530389)Shanghai Rising-Star Project(No.18QB1400500),The Key Clinical Medicine Center of Shanghai(No.2017ZZ01006)+2 种基金Sanming Project of Medicine in Shenzhen(No.SZSM201612078)The Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201714)Development Project of Shanghai Peak Disciplines-Integrative Medicine(No.20180101).
文摘The peripheral nervous system(PNS)is essential for performing and maintaining various motor and sensory functions.Abnormalities can lead to a series of peripheral neurological conditions,such as paraesthesia,pain,or spasms,which are debilitating and lowering the quality of life.Thecurrent guidelines for diagnosis rely predominantly on clinical symptoms resulting from PNS dysfunction,which occur already at an advancedstage.There are currently no effective methods that visually reflect the extent of peripheral neuropathy.In our study,we present a novel in vivoand in situ real-time imaging of peripheral nerves based on the second near-infrared window(NIR-II)fluoresce nee.In NIR-II system,lead sulfidequa ntum dots(PbS Qds)with NIR-II fluoresce nee specifically bound to motor neuro rvspecific protein agrin,acting as image con trast.In micemodel,peripheral nerves were visible as soon as after 2 h post injection.We provide evidenee for the efficacy of this approach,which allows todirectly dem on strate peripheral nerves,their structure,and pote ntial damagesites and degree.Furthermore,our products were of goodbiocompatibility,while the n eural fluoresce nee signal was solid,bright and stable for 4 h in vivo.Thus,overall,our results suggest that NIR-II isan effective new method for direct imaging of peripheral nerves in vivo,opening new horizons on early,improved and more precise,targeteddiag no sis.A resulti ng more rapid installatio n of perso nalized therapy facilitates a better prognosis of clinical peripheral neuropathy.
