The role of purinergic signaling in acupuncture-mediated relief of neuropathic and inflammatory pain.

Acupuncture is a traditional medicinal practice in China that has been increasingly recognized in other countries in recent decades. Notably, several reports have demonstrated that acupuncture can effectively aid in pain management. However, the analgesic mechanisms through which acupuncture provides such benefits remain poorly understood. Purinergic signaling, which is mediated by purine nucleotides and purinergic receptors, has been proposed to play a central role in acupuncture analgesia. On the one hand, acupuncture affects the transmission of nociception by increasing adenosine triphosphate dephosphorylation and thereby decreasing downstream P2X3, P2X4, and P2X7 receptors signaling activity, regulating the levels of inflammatory factors, neurotrophic factors, and synapsin I. On the other hand, acupuncture exerts analgesic effects by promoting the production of adenosine, enhancing the expression of downstream adenosine A1 and A2A receptors, and regulating downstream inflammatory factors or synaptic plasticity. Together, this systematic overview of the field provides a sound, evidence-based foundation for future research focused on the application of acupuncture as a means of relieving pain.

Flexible needle-type Microbiosensor for real-time monitoring traditional acupuncture-mediated adenosine release In vivo.

Rapid adenosine (ADO) signaling, on the time frame of seconds, regulates physiological and pathological processes, including the therapeutic efficacy of acupuncture. Nevertheless, standard monitoring strategies are limited by poor temporal resolution. Herein, an implantable needle-type microsensor capable of monitoring ADO release in vivo in response to acupuncture in real time has been developed. Electrocatalytic Prussian Blue nanoparticles, an immobilized multienzyme system, and a permselective poly-o-phenylenediamine-based membrane were used for the sequential modification of the sensing region of the electrode. The resultant sensor can perform amperometric measurements of ADO levels in response to a very low level of applied potential (-0.05 V vs Ag/AgCl). This microsensor also functioned across a broad linear range (0-50 µM) and exhibited good sensitivity (1.1 nA/µM) with a rapid response time of under 5 s. Importantly, the sensor also exhibited good reproducibility and high selectivity. For in vivo animal studies, the microsensor was employed for the continuous assessment of instantaneous ADO release at the ST36 (Zusanli) acupoint when this acupoint was subjected to twirling-rotating acupuncture manipulation. Benefiting from superior sensor in vivo performance and stability, the positive correlation between the variability in acupuncture-induced ADO release and the stimulus intensity levels that affect the clinical benefit can be demonstrated for the first time. Overall, these results highlight a powerful approach to analyzing the in vivo physiological effects of acupuncture, expanding application realm of micro-nano sensor technology on a fast time scale.

The mechanistic basis for the effects of electroacupuncture on neuropathic pain within the central nervous system.

Nociceptive signaling responses to painful stimuli are transmitted to the central nervous system (CNS) from the afferent nerves of the periphery through a series of neurotransmitters and associated signaling mechanisms. Electroacupuncture (EA) is a pain management strategy that is widely used, with clinical evidence suggesting that a frequency of 2-10 Hz is better able to suppress neuropathic pain in comparison to higher frequencies such as 100 Hz. While EA is widely recognized as a viable approach to alleviating neuralgia, the mechanistic basis underlying such analgesic activity remains poorly understood. The present review offers an overview of current research pertaining to the mechanisms whereby EA can alleviate neuropathic pain in the CNS, with a particular focus on the serotonin/norepinephrine, endogenous opioid, endogenous cannabinoid, amino acid neurotransmitter, and purinergic pathways. Moreover, the corresponding neurotransmitters, neuromodulatory compounds, neuropeptides, and associated receptors that shape these responses are discussed. Together, this review seeks to provide a robust foundation for further studies of the EA-mediated alleviation of neuropathic pain.

Adenosine signaling mediate pain transmission in the central nervous system.

Pain is a common clinical symptom that seriously affects the quality of life in a variety of patient populations. In recent years, research on the role of adenosine signaling in pain modulation has made great progress. Adenosine is a purine nucleoside and a neuromodulator, and regulates multiple physiological and pathophysiological functions through the activation of four G protein-coupled receptors, which are classified as A1, A2A, A2B, and A3 adenosine receptors (ARs). Adenosine and its receptors that are widespread in the central nervous system (CNS) play an important role in the processing of nociceptive sensory signals in different pain models. A1Rs have the highest affinity to adenosine, and the role in analgesia has been well investigated. The roles of A2ARs and A2BRs in the modulation of pain are controversial because they have both analgesic and pronociceptive effects. The analgesic effects of A3Rs are primarily manifested in neuropathic pain. In this article, we have reviewed the recent studies on ARs in the modulation of neuropathic pain, inflammatory pain, postoperative pain, and visceral pain in the CNS. Furthermore, we have outlined the pathways through which ARs contribute to pain regulation, thereby shedding light on how this mechanism can be targeted to provide effective pain relief.

Carbon Nanomaterials-Based Electrochemical Sensors for Heavy Metal Detection.

Heavy metals are commonly found in a wide range of environmental settings metals, but the potential toxicity associated with heavy metal exposure represents a major threat to global public health. It is thus vital that approaches to efficiently, reliably, and effectively detecting heavy metals in a range of sample types be established. Carbon nanomaterials offer many advantageous properties that make them well-suited to the design of sensitive, selective, easy-to-operate electrochemical biosensors ideal for detecting heavy metal ions. The present review offers an overview of recent progress in the development of carbon nanomaterial-based electrochemical sensors used to detect heavy metals. In addition to providing a detailed discussion of certain carbon nanomaterials such as carbon nanotubes, graphene, carbon fibers, carbon quantum dots, carbon nanospheres, mesoporous carbon, and Graphdiyne, we survey the challenges and future directions for this field. Overall, the studies discussed herein suggest that the further development of carbon nanomaterial-modified electrochemical sensors will support the integration of increasingly advanced sensor platforms to aid in detecting heavy metals in foods, environmental samples, and other settings, thereby benefitting human health and society as a whole.

Recent Advances in Metal Nanocomposite-Based Electrochemical (Bio)Sensors for Pharmaceutical Analysis.

Rising rates of drug abuse and pharmaceutical pollution throughout the world as a consequence of increased drug production and utilization pose a serious risk to public health and to environmental integrity. It is thus critical that reliable analytical approaches to detecting drugs and their metabolites in a range of sample matrices be developed. Recent advances in the design of nanomaterial-based electrochemical sensors and biosensors have enabled promising new approaches to pharmaceutical analysis. In particular, the development of a range of novel metal nanocomposites with enhanced catalytic properties has provided a wealth of opportunities for the design of rapid and reliable platforms for the detection of specific pharmaceutical compounds. The present review provides a comprehensive overview of representative metal nanocomposites with synergistic properties and their recent (2017-2022) application in the context of electrochemical sensing as a means of detecting specific antibiotic, tuberculostatic, analgesic, antineoplastic, antipsychotic, and antihypertensive drugs. In discussing these applications, we further explore a variety of testing-related principles, fabrication approaches, characterization techniques, and parameters associated with the sensitivity and selectivity of these sensor platforms before surveying the future outlook regarding the fabrication of next-generation (bio)sensor platforms for use in pharmaceutical analysis.

Expression of glia maturation factor γ is associated with colorectal cancer metastasis and its downregulation suppresses colorectal cancer cell migration and invasion in vitro.

Glia maturation factor γ (GMFG) functions to reorganize the actin cytoskeleton and appears to play a causative role in cell migration and adherence. The present study assessed GMFG expression in colorectal cancer cells and tissue specimens and then explored the role of GMFG in colorectal cancer progression in vitro. GMFG protein was highly expressed in colorectal cancer tissues and a metastatic colon cancer cell line. Knockdown of GMFG expression using GMFG siRNA or anti-GMFG antibody decreased the capacity of colon cancer LoVo cell migration and invasion in vitro, while recombinant GMFG treatment induced LoVo cell migration. Furthermore, GMFG knockdown also decreased expression of MMP2 protein and reversed epithelial-mesenchymal transition (EMT) phenotypes in LoVo cells. Co-culture of LoVo cells with human umbilical vein endothelial cells (HUVECs) and exogenous GMFG treatment promoted LoVo cell migration and invasion. The data from the present study indicate that GMFG should be further evaluated as a biomarker for detection of colorectal cancer metastasis and that the targeting of GMFG expression or function could be a novel strategy in the future control of colorectal cancer.

Ethanol reduces neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.

OBJECTIVE: To investigate the influence of exposure to different concentrations of ethanol on neural progenitor cells and the differentiation of neurons and glial cells in zebrafish embryos. METHODS: Zebrafish embryos were exposed to 1%, 2%, and 2.5% (V/V) ethanol at 5 hpf by adding ethanol to the egg water. In situ hybridization and real-time PCR were used to detect the changes in the mRNA expression profiles of the markers of different cells to examine the effects of alcohol on neural development. RESULTS: The number of neural precursor cells, neurons and mature glial cells was significantly reduced in the zebrafish embryos following ethanol exposure, and this reduction became more prominent as the ethanol concentration increased. The expression of the early glial marker slc1a3a was down-regulated in the spinal cord but increased in the brain after exposure to increased ethanol concentrations. The expression of the mature glial markers was significantly lowered in response to exposure to increasing ethanol concentrations. CONCLUSIONS: Ethanol can reduce neural precursor cells and inhibits neuronal and glial differentiation in zebrafish embryos.

[Pulmonary expression levels of fibroblast growth factor receptors and lung fibrosis in mice at different ages].

OBJECTIVE: To explore the correlation of pulmonary expressions of fibroblast growth factor receptors (FGFR1-4) with lung fibrosis and aging. METHODS: Real-time fluorescence quantitative PCR was used to detect the expression levels of FGFR1-4 in the lung tissues, and lung fibrosis was observed by HE and Masson staining in mice at different ages. RESULTS: The 4 subtypes of FGFR showed different expression levels in the lung tissues of mice, and FGFR2 had the highest expressions. The expression levels of all the 4 FGFR subtypes in 8-month-old mice were significantly lower than those in 5-week-old mice. The 8-month-old mice tended to present with histological changes of lung fibrosis. CONCLUSION: FGFR expressions is down-regulated with aging in mice. Among the FGFR subtypes, FGFR2 is expressed at the highest level. The occurrence of lung fibrosis with aging is probably associated with down-regulated FGFR expression. FGF/FGFR signaling may participate in the aging process and regulation of lung fibrosis.

Silver deposits in cutaneous burn scar tissue is a common phenomenon following application of a silver dressing.

BACKGROUND: Silver dressings have been widely and successfully used to prevent cutaneous wounds, including burns, chronic ulcers, dermatitis and other cutaneous conditions, from infection. However, in a few cases, skin discolouration or argyria-like appearances have been reported. This study investigated the level of silver in scar tissue post-burn injury following application of Acticoat, a silver dressing. METHODS: A porcine deep dermal partial thickness burn model was used. Burn wounds were treated with this silver dressing until completion of re-epithelialization, and silver levels were measured in a total of 160 scars and normal tissues. RESULTS: The mean level of silver in scar tissue covered with silver dressings was 136 microg/g, while the silver level in normal skin was less than 0.747 microg/g. A number of wounds had a slate-grey appearance, and dissection of the scars revealed brown-black pigment mostly in the middle and deep dermis within the scar. The level of silver and the severity of the slate-grey discolouration were correlated with the length of time of the silver dressing application. CONCLUSIONS: These results show that silver deposition in cutaneous scar tissue is a common phenomenon, and higher levels of silver deposits and severe skin discolouration are correlated with an increase in the duration of this silver dressing application.

Silver absorption on burns after the application of Acticoat: data from pediatric patients and a porcine burn model.

Silver dressings have been widely used to successfully prevent burn wound infection and sepsis. However, a few case studies have reported the functional abnormality and failure of vital organs, possibly caused by silver deposits. The aim of this study was to investigate the serum silver level in the pediatric burn population and also in several internal organs in a porcine burn model after the application of Acticoat. A total of 125 blood samples were collected from 46 pediatric burn patients. Thirty-six patients with a mean of 13.4% TBSA burns had a mean peak serum silver level of 114 microg/L, whereas 10 patients with a mean of 1.85% TBSA burns had an undetectable level of silver (<5.4 microg/L). Overall, serum silver levels were closely related to burn sizes. However, the highest serum silver was 735 microg/L in a 15-month-old toddler with 10% TBSA burns and the second highest was 367 microg/L in a 3-year old with 28% TBSA burns. In a porcine model with 2% TBSA burns, the mean peak silver level was 38 microg/L at 2 to 3 weeks after application of Acticoat and was then significantly reduced to an almost undetectable level at 6 weeks. Of a total of four pigs, silver was detected in all four livers (1.413 microg/g) and all four hearts (0.342 microg/g), three of four kidneys (1.113 microg/g), and two of four brains (0.402 microg/g). This result demonstrated that although variable, the level of serum silver was positively associated with the size of burns, and significant amounts of silver were deposited in internal organs in pigs with only 2% TBSA burns, after application of Acticoat.

The efficacy of Aloe vera, tea tree oil and saliva as first aid treatment for partial thickness burn injuries.

Many alternative therapies are used as first aid treatment for burns, despite limited evidence supporting their use. In this study, Aloe vera, saliva and a tea tree oil impregnated dressing (Burnaid) were applied as first aid to a porcine deep dermal contact burn, compared to a control of nothing. After burn creation, the treatments were applied for 20 min and the wounds observed at weekly dressing changes for 6 weeks. Results showed that the alternative treatments did significantly decrease subdermal temperature within the skin during the treatment period. However, they did not decrease the microflora or improve re-epithelialisation, scar strength, scar depth or cosmetic appearance of the scar and cannot be recommended for the first aid treatment of partial thickness burns.

Conservative surgical debridement as a burn treatment: supporting evidence from a porcine burn model.

In thermal deep-dermal burns, surgical debridement is normally used in conjunction with skin grafting or skin substitutes and debridement alone as a burn treatment is not usually practiced. The current study addresses whether or not debridement alone would enhance burn wound healing on small deep-dermal-partial thickness burns. This was a prospective and blinded experimental trial using a porcine deep-dermal-partial thickness burn model. Four burns, approximately 50 cm(2) in size, were created on each of eight pigs. Two burns from each pig were immediately surgically debrided and the other two were not debrided as the internal control. Hydrate gel together with paraffin gauze were used to cover the burns for four pigs and silver dressings for the other four. Clinical assessment of wound healing was conducted over a 6-week period. Skin samples were collected at the end of the experiment and histopathological evaluation was performed. The results show thinner scar formation and lower scar height in the debrided compared with nondebrided wounds in the hydrate gel/paraffin gauze groups. There were no statistically significant differences in wound healing assessment between the debrided and nondebrided wounds dressed with silver dressings. This study provides supporting evidence that immediate debridement with an appropriate dressing and without skin grafting may promote wound healing, suggesting its potential benefit for clinical patients.