Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice.

Precise monitoring of internal temperature is vital for thermal homeostasis in mammals. For decades, warm-sensitive neurons (WSNs) within the preoptic area (POA) were thought to sense internal warmth, using this information as feedback to regulate body temperature (Tcore). However, the cellular and molecular mechanisms by which WSNs measure temperature remain largely undefined. Via a pilot genetic screen, we found that silencing the TRPC4 channel in mice substantially attenuated hypothermia induced by light-mediated heating of the POA. Loss-of-function studies of TRPC4 confirmed its role in warm sensing in GABAergic WSNs, causing additional defects in basal temperature setting, warm defense, and fever responses. Furthermore, TRPC4 antagonists and agonists bidirectionally regulated Tcore. Thus, our data indicate that TRPC4 is essential for sensing internal warmth and that TRPC4-expressing GABAergic WSNs function as a novel cellular sensor for preventing Tcore from exceeding set-point temperatures. TRPC4 may represent a potential therapeutic target for managing Tcore.

Low Electrical Resistance Properties of Acupoints: Roles of NOergic Signaling Molecules and Neuropeptides in Skin Electrical Conductance.

Early studies from several independent laboratories demonstrated that acupoints possess the characteristics of low electrical resistance. New devices are developing to increase the reliability of electrical skin impedance measurements for counteracting the factors including skin dryness, skin thickness, size of the sensing electrode, pressure applied on the electrode, interelectrode distance, room temperature, and humidity. Morphological studies have identified that blood vessels, hair follicles, and nervous components are enhanced in the meridians/acupoints, which represent areas of potentially high neuronal activity. Recent evidence shows that nitric oxide (NO) concentrations are enhanced in skin acupoints/meridians. L-arginine-derived NO synthesis modifies skin norepinephrine (NE) synthesis/release in acupoints/meridians, and NO-NE activations play an important role in mediating the skin conductance responses to electrical stimulation. NOergic signaling molecules interact with gap junction and transient receptor potential vanilloid type-1. Other studies reported that the high conductance at acupoints is a result of the release of the neuropeptides substance P and calcitonin gene-related peptide during neurogenic inflammation in the referred pain area. Pathological body conditions caused considerable changes in skin conductance or impedance at acupoints. Although systematic research with an improved equipment and research design to avoid the influencing factors are requested for a definite answer in this field, the results from anatomical and biochemical studies consistently show that acupoints exist higher levels of nervous components, and NOergic signaling molecules and neuropeptides involved in the skin low resistance at acupoints. The increased interest in the acupoints/meridians has led to an open-minded attitude towards understanding this system, which is fundamental important to establish the valid aspects of scientific basis of Chinese medicine mechanisms and therapies.

Nitric Oxide on Pathophysiology of SARS-CoV 19: Toward Possible Role of Acupuncture Treatment.

The ongoing outbreak of COVID-19 has quickly become a daunting challenge to global health. In the absence of satisfied therapy, effective treatment interventions are urgently needed. Previous studies have demonstrated that acupuncture is effective at relieving common symptoms of COVID-19 including breathlessness, nausea, insomnia, leukopenia, fatigue, vomiting, and abdominal pain. Experiments have shown that nitric oxide (NO) inhibits the replication cycle of severe acute respiratory syndrome (SARS) coronavirus with similar structures of COVID-19. Increase in level of NO by using NO gas inhalation has been shown to restore lung function by reducing airway resistance and improving virus-induced lung infections in SARS patients. Recent case report showed that a medical acupuncturist with symptoms consistent with severe COVID pneumonia achieved full recovery by self-administered medical acupuncture and cupping therapy at home. Clinical features and pathophysiology demonstrated that NO deficiency and endothelial dysfunction contribute to the development of COVID-19. Several studies from different groups consistently demonstrated that acupuncture increases NO synthase expression and induces an elevation of NO production and release in plasma and the local skin regions in both animals and humans. It is suggested that exogenous NO supplies or interventions that induce increasing levels of NO can play an important role in protective effects against inflammation and acute lung injury. This article reviews the rationale for mechanisms of NO induction induced by acupuncture in the possible treatment of COVID-19 and highlights its potential for contributing to better clinical outcomes and improving future clinical studies of acupuncture on treatment of COVID-19.

Effects of electroacupuncture plus drug anesthesia on pain and stress response in patients after radical surgery for stomach cancer / 针灸推拿医学（英文版）

Objective: To observe the effect of electroacupuncture plus drug anesthesia on pain and stress response in patients after radical surgery for stomach cancer.Methods: A total of 60 patients were randomized into a control group and an observation group by the random number table, with 30 cases in each group. The control group was given conventional drug anesthesia. The observation group was given additional electroacupuncture intervention. Before anesthesia and 2 h, 12 h and 24 h after surgery, the visual analog scale (VAS) was scored, the heart rate, the mean arterial pressure, and the levels of serum β-endorphin (β-EP) and adrenocorticotrophic hormone (ACTH) were measured. Results: Two hours, 12 h and 24 h after surgery, the VAS scores of both groups were higher than those before anesthesia (all P<0.05), and the VAS scores in the observation group were lower than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the heart rates and mean arterial pressures in the control group were significantly higher than those before anesthesia (all P<0.05), while there were no significant intra-group differences in the observation group (all P>0.05), and the indicators were lower than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the serum β-EP levels in the observation group were significantly higher than those before anesthesia (all P<0.05), and significantly higher than those in the control group at the same time points (all P<0.05). Two hours, 12 h and 24 h after surgery, the serum ACTH levels in the control group were significantly higher than those before anesthesia (all P<0.05), and were significantly higher than those in the observation group at the same time points (all P<0.05). Conclusion: Electroacupuncture plus drug anesthesia can significantly relieve pain and stress response in patients after radical surgery for stomach cancer.

Establishing an adequate dose of acupuncture is essential for clinical trial studies.

Importance: A number of recent clinical trials have demonstrated that acupuncture is more effective for treating chronic pain conditions compared to sham and no acupuncture, but some research questions have remained unaddressed and are standing in the way of further progress. Observations and Advances: The effectiveness of acupuncture for pain conditions compared to usual care have been demonstrated, which has significantly enhanced the position of acupuncture in multiple pain guidelines following these studies. However, the studies also generated some conflicting results with difficulty in comparing each other. Research examining an adequate dose of acupuncture therapy with optimal intervention parameters and time table has also long been neglected and is now urgent. The dose of acupuncture depends on stimulation parameters: force/intensity and speed/frequency of manual acupuncture (MA) or electroacupuncture (EA) and time table (number of treatment sessions and duration). Various frequencies and intensities of MA and EA stimulation have been utilized in individual research. Different acupuncture treatment sessions (once, twice, three to five times per week) and periods (4, 6, 8, and 12 weeks) have been used in these clinical trials. One clinical trial using one session of needle acupuncture and laser at 12 weeks (8 to 12 treated sessions) did not improve pain in patients with chronic knee pain but similar trials of osteoarthritis knee have significant effects of pain improvement after biweekly sessions of needle acupuncture for 8 weeks of treatment. Conclusions and Relevance: Determining a right treatment regimen on correct acupuncture point(s) for acupuncture is a critical first step for acupuncture clinical trials. Appropriate acupuncture parameters such as acupuncture stimulation technique, treatment sessions, and treatment duration must be considered in acupuncture clinical trials. An adequate dose of acupuncture for clinical trials should be established following dose finding workshops for acupuncture before the studies, which not only improve the therapeutic effects of the therapies but also allow the comparisons between trials and between the acupuncture community/practice and trial studies.

Electrochemically triggered degradation of silicon membranes for smart on-demand transient electronic devices.

Transient electronics is an emerging technology that enables unique functional transformation or the physical disappearance of electronic devices, and is attracting increasing attention for potential applications in data secured hardware as an ultimate solution against data breaches. Developing smart triggered degradation modalities of silicon (Si) remain the key challenge to achieve advanced non-recoverable on-demand transient electronics. Here, we present a novel electrochemically triggered transience mechanism of Si by lithiation, allowing complete and controllable destruction of Si devices. The depth and microstructure of the lithiation-affected zone over time is investigated in detail and the results suggest a few hours of lithiation is sufficient to create microcracks and significantly promote lithium penetration. Finite element models are proposed to confirm the mechanism. Electrochemically triggered degradation of thin film Si ribbons and Si integrated circuit chips with metal-oxide-semiconductor field-effect transistors from a commercial 0.35 micrometer complementary metal-oxide-semiconductor technology node is performed to demonstrate the potential applications for commercial electronics. This work opens new opportunities for versatile triggered transience of Si-based devices for critical secured information systems and green consumer electronics.

Chemical Constituents and Pharmacological Activities of Rosmarini Officinalis Herba / 中国实验方剂学杂志

Rosmarini Officinalis Herba is a common shrubby aromatic plant, which is widely used in traditional food and folk medicine. At present, most of relevant researches focus on rosemary's essential oil, ethanol and water extract, which not only plays an important role in food preservation, preservation and condiments, but also is often used to improve acne, dandruff, circulation function, alleviate muscle pain and fatigue and treat asthma, bronchitis. It has a high application value, and a variety of other pharmacological effects. However, Rosmarini Officinalis Herba has not been included in the Chinese Pharmacopoeia, with no quality evaluation standard for its medicinal use. The products in the market may have some potential safety hazards in the use process. Therefore, the full understanding of the chemical constituents and pharmacological effects of rosemary is crucial for a comprehensive study of the properties and applications of Rosmarini Officinalis Herba. Through the collation and analysis of relevant literatures at home and abroad, it is concluded that Rosmarini Officinalis Herba has anti-cancer, anti-bacterial, anti-oxidation, anti-inflammatory, anti-depression and other pharmacological effects. The chemical constituents extracted from Rosmarini Officinalis Herba are rich in acid phenols, flavonoids, terpenoids and essential oils. Up to now, there are no systematic and comprehensive report on the chemical constituents and pharmacological effects of Rosmarini Officinalis Herba. This paper reviews the progress of the researches on the chemical constituents and pharmacological effects of Rosmarini Officinalis Herba, and discusses its application, in the expectation to lay a foundation for the future research on food development, drug research and clinical application of rosemary.

Anti-leukemia Mechanism and Problems of Volatile Oil from Traditional Chinese Medicine / 中国实验方剂学杂志

Leukemia is a hematopoietic hyperplastic disease with an increasing incidence year by year, involving bone marrow and lymphatic system. The disease is complex and a highly heterogeneous disease, including a variety of subtypes, with difficulties in treatment and a poor prognosis. Currently, retinoic acid and its derivatives, arsenic are commonly used in clinical treatment as leukemia cell differentiation inducers. However, their clinical range of treatment is mostly restricted to granulocytic leukemia, with a high price and certain toxic and side effects. With the development of molecular genetics, molecular biology, second-generation sequencing and other technologies, the etiology and pathology of leukemia has been significantly studied, but the specific pathogenesis of leukemia has still been unclear. With the further promotion of molecular targeted drugs, chimeric antigen receptor T-cell immunotherapy (CAR-T) and hematopoietic stem cell transplantation, although the treatment of leukemia has entered a new field, compared with traditional chemotherapy, these therapies have high costs, and the long-term efficacy is yet to be further confirmed. After years of basic research and clinical research, traditional Chinese medicine(TCM) volatile oil in the treatment of leukemia has made remarkable achievements. Essential oil can alleviate the toxic and side effect of chemotherapy drugs, effectively prolong or prevent the relapse of leukemia, inhibit the proliferation of leukemia cells, and promote the apoptosis of leukemia cells. In this paper, the authors reviewed relevant domestic and foreign literatures by literature tracking method, summarized the anti-leukemia mechanism of essential oil of TCM, analyzed the characteristics and existing problems of essential oil of TCM, and proposed the improvement direction, in order to provide reference for accelerating the research and development and innovation of essential oil in the treatment of leukemia.

Biocompatible and Implantable Optical Fibers and Waveguides for Biomedicine.

Optical fibers and waveguides in general effectively control and modulate light propagation, and these tools have been extensively used in communication, lighting and sensing. Recently, they have received increasing attention in biomedical applications. By delivering light into deep tissue via these devices, novel applications including biological sensing, stimulation and therapy can be realized. Therefore, implantable fibers and waveguides in biocompatible formats with versatile functionalities are highly desirable. In this review, we provide an overview of recent progress in the exploration of advanced optical fibers and waveguides for biomedical applications. Specifically, we highlight novel materials design and fabrication strategies to form implantable fibers and waveguides. Furthermore, their applications in various biomedical fields such as light therapy, optogenetics, fluorescence sensing and imaging are discussed. We believe that these newly developed fiber and waveguide based devices play a crucial role in advanced optical biointerfaces.

Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture.

Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupoints and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide (NO) level is elevated in the acupoints/ meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx- (total nitrite and nitrate) and cyclic guanosine monophosphate (cGMP) concentrations are consistently increased over skin acupoints compared to non-meridian control regions (NMCR) in humans. Dermal microdialysis in humans showed that NO-cGMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture (EA). Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints, and selecting well-trained acupuncturetists for using correct acupoints and appropriate parameters should improve acupuncture clinical trial studies.

Response of Local Nitric Oxide Release to Manual Acupuncture and Electrical Heat in Humans: Effects of Reinforcement Methods.

This study was to examine the influences of manual acupuncture (MA) and electrical heat corresponding to reinforcing methods on nitric oxide (NO) release over the skin regions in humans. A device with collecting solution was taped to the skin surface along pericardium (PC) or lung (LU) meridian. Acupuncture needles were gently inserted into PC 4 with reinforcing stimulation (low force/rate) for 20 minutes in the MA group. LU11 on the finger was heated (43-44°C) by electrical heat for 20 minutes. Biocapture was consecutively conducted for two 20-minute intervals during and after each treatment. Total nitrite and nitrate (NO x-) in the collecting samples were quantified using chemiluminescence in blinded fashion. Baseline NO x- levels are higher and tended to be higher over PC and LU acupoints during the 1st biocapture. NO x- levels over PC regions were consistently increased by MA during both intervals. NO x- concentrations over LU acupoints were increased and tended to be increased by electrical heat in the 1st and 2nd biocapture. The results suggest that reinforcing MA and electrical heat induce NO released from the local skin regions with higher levels at acupoints, which improve local circulation and contribute to the beneficial effects of the therapies.

Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture / 中国结合医学杂志

Recent clinical trial studies have demonstrated that the effects of acupuncture on pain improvement are small and no difference between acupoints and non-points. Whether acupuncture needles must be inserted in specific points depends on whether acupoint specificity exists that is still not resolved, and is now urgent. Previous anatomical studies have demonstrated that acupoints exist higher number of nerve fibers/trunks, blood vessels, hair follicles, and sweat glands as well as density of the gap junction. Recent evidence shows that nitric oxide (NO) level is elevated in the acupoints/ meridians and is associated with an enhanced expression of NO synthase endowed with transient receptor potential vanilloid type-1. There is growing evidence from international groups showing that acupuncture induces NO-mediated vasodilatation, which increases local blood flow and allows for a flush of algesic or sensitizing substances, leading to pain relief. Previous studies, using a novel biocapture system, have demonstrated that NOx(total nitrite and nitrate) and cyclic guanosine monophosphate (cGMP) concentrations are consistently increased over skin acupoints compared to non-meridian control regions (NMCR) in humans. Dermal microdialysis in humans showed that NO-cGMP releases in the subcutaneous tissue of acupoint are higher than those in NMCR and increased by electroacupuncture (EA). Recent studies have demonstrated that low-frequency electrical stimulation and manual acupuncture with low stimulating force and rate produce an elevation of NO release predominantly over acupoints. In contrast, NO levels over the areas of the skin regions are moderately reduced by high-frequency EA stimulation. The results from anatomical and biochemical studies consistently show that acupoints exist higher levels of NO signaling molecules, and stimulus-evoked NO release is also with a higher level at acupoints. Results suggest that NO signaling molecules contribute to the specificity of acupoints, and selecting well-trained acupuncturetists for using correct acupoints and appropriate parameters should improve acupuncture clinical trial studies.

Battery-free, stretchable optoelectronic systems for wireless optical characterization of the skin.

Recent advances in materials, mechanics, and electronic device design are rapidly establishing the foundations for health monitoring technologies that have "skin-like" properties, with options in chronic (weeks) integration with the epidermis. The resulting capabilities in physiological sensing greatly exceed those possible with conventional hard electronic systems, such as those found in wrist-mounted wearables, because of the intimate skin interface. However, most examples of such emerging classes of devices require batteries and/or hard-wired connections to enable operation. The work reported here introduces active optoelectronic systems that function without batteries and in an entirely wireless mode, with examples in thin, stretchable platforms designed for multiwavelength optical characterization of the skin. Magnetic inductive coupling and near-field communication (NFC) schemes deliver power to multicolored light-emitting diodes and extract digital data from integrated photodetectors in ways that are compatible with standard NFC-enabled platforms, such as smartphones and tablet computers. Examples in the monitoring of heart rate and temporal dynamics of arterial blood flow, in quantifying tissue oxygenation and ultraviolet dosimetry, and in performing four-color spectroscopic evaluation of the skin demonstrate the versatility of these concepts. The results have potential relevance in both hospital care and at-home diagnostics.

[Analysis of the Puzzle between Acupuncture Community and Acupuncture Clinical Trials].

Recently a number of acupuncture clinical trial projects mainly conducted by conventional scientists have generated many negative results. A large meta-analysis of patient-level acupuncture data for the treatment of chronic pain conditions have demonstrated that the effects of verum acupuncture on pain improvement have statistically significant, but small, differences compared with sham-acupuncture procedures and no difference between acupuncture points and non-points. These conclusions have puzzled the acupuncture community and made confusion for acupuncture research and practices. The purpose of this paper was to compare differences between acupuncture clinical practices and the trial studies, which include "acupuncture technical principles", "acupuncture clinical trial design", and "acupuncture practice based on the theory of traditional Chinese medicine". These factors contribute to the puzzle between the acupuncture community/practice and acupuncture clinical trials, which can be improved in future studies.

Analysis of the Puzzle between Acupuncture Community and Acupuncture Clinical Trials / 中国中西医结合杂志

Recently a number of acupuncture clinical trial projects mainly conducted by conventional scientists have generated many negative results. A large meta-analysis of patient-level acupuncture data for the treatment of chronic pain conditions have demonstrated that the effects of verum acupuncture on pain improvement have statistically significant, but small, differences compared with sham-acupuncture procedures and no difference between acupuncture points and non-points. These conclusions have puzzled the acupuncture community and made confusion for acupuncture research and practices. The purpose of this paper was to compare differences between acupuncture clinical practices and the trial studies, which include "acupuncture technical principles", "acupuncture clinical trial design", and "acupuncture practice based on the theory of traditional Chinese medicine". These factors contribute to the puzzle between the acupuncture community/practice and acupuncture clinical trials, which can be improved in future studies.

Influence of age, gender, and race on nitric oxide release over acupuncture points-meridians.

This study examined the influence of age, gender and race on nitric oxide (NO) release over acupuncture points, meridian without acupoint, and non-meridian regions of the Pericardium (PC) and Bladder (BL) meridian as well as aging on LU meridian in 61 healthy subjects. Biocapture tubes were attached to the skin surface, and total nitrite and nitrate was biocaptured and quantified using chemiluminescence. In elder ages compared to adults, NO levels over the ventral forearm were significantly decreased over LU on radial regions but not altered over PC on medial regions. Conversely, NO content was elevated over BL regions only in overweight/obesity of elder ages. NO levels over PC regions were marginally elevated in overweight/obese males compared to females but did not alter between races. These results suggest a selective reduction of NO release over LU meridian with aging, which is consistent with a progressive decline in lung function and increase in chronic respiratory disease in elder ages. Increased NO levels along the BL meridian in older obese subjects may reflect a modified NO level along somatic-bladder pathway for counteracting bladder dysfunctions with aging. Both of them support somatic-organ connections in the meridian system associated with potential pathophysiological changes with aging.

Transcutaneous Electrical Stimulation Increased Nitric Oxide-Cyclic GMP Release Biocaptured Over Skin Surface of Pericardium Meridian and Acupuncture Points in Humans.

OBJECTIVES: The purpose of this study was to consecutively capture and quantify nitric oxide (NO) and cGMP, the second messenger of NO, over the skin surface of acupuncture points (acupoints), meridian line without acupoint, and non-meridian control regions of the Pericardium meridian (PC) in humans, and investigate their response to transcutaneous electrical nerve stimulation (TENS) . DESIGN, SETTING, AND MAIN OUTCOME MEASURES: Adhesive biocapture tubes were attached to the skin surface along PC regions and injected with 2-Phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl solution, an NO-scavenging compound, contacting the skin surface for 20 minutes each during 4 consecutive biocapture intervals. TENS (1.0 mA, 6 Hz, 1.0 msec duration) was applied over acupoints PC 8 and PC 3 during the 2nd biocapture for 20 min. Total nitrite and nitrate (NO(x)-), the stable metabolic products of NO, and cGMP in biocaptured samples were quantified using chemiluminescence and ELISA. RESULTS: NO(x)- levels in the 1st biocapture over PC regions are almost two fold higher compared to subsequent biocaptures and are higher over PC acupoints versus non-meridian control region. Following TENS, NO(x)- concentrations over PC regions were significantly increased, and cGMP is predominantly released from the skin surface of PC acupoints. CONCLUSIONS: TENS induces elevations of NO-cGMP concentrations over local skin region with a high level at acupoints. The enhanced signal molecules improve local circulation, which contributes to beneficial effects of the therapy.

Infrared heat treatment reduces food intake and modifies expressions of TRPV3-POMC in the dorsal medulla of obesity prone rats.

PURPOSE: Infrared heat, a transient receptor potential vanilloid type-3 (TRPV3) sensitive stimulus, may have potential physiological effects beneficial to treating metabolic syndrome. MATERIALS AND METHODS: Obesity prone (OP) and obesity resistant (OR) rats were fed for seven days on a high-fat diet. Heat treated OP rats were exposed twice daily to infrared light for 20 min each, separated by 80 min of rest. Food intake, blood pressure, blood glucose, and body weight measurements were taken daily and compared between treated OP rats, untreated OP rats, and OR controls. The animals were perfused with 4% paraformaldehyde, and immunohistochemistry was performed on the coronal brainstem sections with polyclonal antibodies against TRPV3 and pro-opiomelanocortin (POMC). The positive-staining cells in the medulla nuclei were quantified using a microscope with reticule grid. RESULTS: Food intake, body weight, and mean arterial blood pressure (MAP) were higher in OP rats, a diet-induced metabolic syndrome model, accompanied by a reduced expression of POMC, an anorectic agent, in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS). Food intake in heat-treated OP rats was significantly decreased. POMC positive neuron count was increased in the HN and mNTS of OP rats following treatment. TRPV3 positive staining neurons were increased in the HN and mNTS of OP control rats and decreased following the heat treatments. CONCLUSION: Lowered POMC and heightened TRPV3 expressions in the HN and mNTS are involved in development of hyperphagia and obesity in OP rats. Exposure to infrared heat modifies TRPV3 and POMC expression in the brainstem, reducing food intake.

TRPV1 expression in acupuncture points: response to electroacupuncture stimulation.

The present study was to examine the distribution of transient receptor potential vanilloid type-1 (TRPV1) receptor immunoreactivity in the acupuncture points (acupoint), and determine the influences of electroacupuncture (EA) stimulation on TRPV1 expression. EA stimulation of BL 40 was conducted in two sessions of 20 min separated by an 80 min interval in anesthetized rats. Sections of skin containing BL 40, and its non-meridian control were examined by immunolabeling with antibodies directed against TRPV1. Without EA, the number of subepidermal nerve fibers expressing TRPV1 was higher in the acupoint than in non-acupoint control skin (p<0.01). The subepidermal nerve fibers showed the co-localization of TRPV1 with peripherine, a marker for the C-fibers and A-δ fibers. The expression of TRPV1 in nerve fibers is significantly increased by EA stimulation in acupoints (p<0.01). However the upregulation in the non acupoint meridian and the non-meridian control skin was short of statistical significance. Double immunostaining of TRPV1 and neuronal nitric oxide synthase (nNOS) revealed their co-localization in both the subepidermal nerve fibers and in the dermal connective tissue cells. These results show that a high expression of TRPV1 endowed with nNOS in subepidermal nerve fibers exists in the acupoints and the expression is increased by EA. We conclude that the higher expression of TRPV1 in the subepidermal nerve fibers and its upregulation after EA stimulation may play a key role in mediating the transduction of EA signals to the CNS, and its expression in the subepidermal connective tissue cells may play a role in conducting the local effect of the EA.

Changes in nitric oxide, cGMP, and nitrotyrosine concentrations over skin along the meridians in obese subjects.

The purposes of these studies were to quantify the concentrations of total nitrate and nitrite (NO(x)(-)) cyclic guanosine monophosphate (cGMP), and nitrotyrosine over skin surface in normal weight healthy volunteers (n = 64) compared to overweight/obese subjects (n = 54). A semi-circular plastic tube was taped to the skin along acupuncture points (acupoints), meridian line without acupoint (MWOP), and nonmeridian control and filled with a 2-Phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl solution for 20 min. The concentrations of NO(x)(-), cGMP, and nitrotyrosine in the samples were quantified in a blinded fashion using chemiluminescence and enzyme-linked immunosorbent assay, respectively. In normal weight healthy volunteers, NO(x)(-) and cGMP concentrations were consistently increased over the pericardium meridian (PC) 4-7 compared with nonmeridian areas. NO(x)(-) concentration is enhanced over the bladder meridian (BL) 56-57, but cGMP level is similar between the regions. In overweight/obese subjects, NO(x)(-) contents were increased or tended to be elevated over PC and BL regions. cGMP is paradoxically decreased over PC acupoints and nonmeridian control on the forearm but the decreases were blunted along BL regions on the leg. Nitrotyrosine concentrations are markedly elevated (five- to sixfold) over both PC and BL in all areas of overweight/obese subjects. This is the first evidence showing that nitrotyrosine level is tremendously elevated over skin accompanied by paradoxical changes in nitric oxide (NO)-cGMP concentrations over PC skin region in overweight/obese subject. The results suggest that NO-related oxidant inflammation is systemically enhanced while cGMP generation is impaired over PC skin region but not over BL region in obesity.