Acupuncture Alleviates Anxiety and 22-kHz Ultrasonic Vocalizations in Rats Subjected to Repeated Alcohol Administration by Modulating the Brain-Derived Neurotrophic Factor/Corticotropin-Releasing Hormone Signaling Pathway.

The Shenmen point (acupuncture point heart 7: HT7), located in the heart meridian, is frequently used to treat mental disorders, including drug addiction, anxiety, and depression. This study aimed to determine how HT7 regulates anxiety and negative emotions caused by repeated alcohol administration, focusing on the amygdala and paraventricular nucleus (PVN). Repeated administration of alcohol (ETOH; 2 g/kg, i.p. injection, 16% v/v) for 14 days increased the corticosterone (CORT) levels, and HT7 stimulation reduced the plasma CORT levels. HT7 stimulation mitigated anxiety-like behaviors and reduced 22-kHz ultrasonic vocalizations in rats receiving repeated ETOH injections. HT7 stimulation increased the amygdala expression of mature brain-derived neurotropic factor (mBDNF) and phosphorylated tropomyosin receptor kinase B (pTrkB) and decreased the PVN corticotropin-releasing hormone (CRH) expression. Amygdala microinjections of the TrkB antagonist ANA-12 (0.1 pmol/1 µL) reversed the increase in PVN CRH levels. The reduced PVN CRH levels were regulated by CRH-expressing neurons in the amygdala, and the increased amygdala CRH levels were affected by the HT7-stimulation induced increases in mBDNF. HT7 stimulation alleviates increased stress hormone levels and mitigates anxiety and negative emotions caused by repeated ETOH administration. These results provide scientific support for the clinical use of acupuncture to treat various alcoholism-induced diseases.

Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area.

There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior. Using microdialysis and in vivo single-unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within-session reinstatement paradigm in rats self-administering cocaine, we evaluated the effects of HT7 stimulation on cocaine-primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine-primed reinstatement, which was blocked by VTA infusions of the selective GABAB receptor antagonist 2-hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine-induced DA release in the NAc, which was also blocked by 2-hydroxysaclofen. HT7 acupuncture also attenuated cocaine-induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle-penetration depth-dependent fashion. These results suggest that acupuncture may suppress cocaine-induced DA release in the NAc and cocaine-seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA.

Change in the P300 index - a pilot randomized controlled trial of low-frequency electrical stimulation of acupuncture points in middle-aged men and women.

BACKGROUND: The P300 is a major index used to evaluate improvements in brain function. Although a few studies have reported evaluating the effectiveness of manual acupuncture or electro-acupuncture by monitoring the P300, research in this field is not yet very active. The aim of this study was to investigate the effects of periodic low-frequency electrical stimulation applied to BL62 and KI6 on brain activity by analyzing the P300. METHOD: The study was conducted as a randomized double-blind test of 55 subjects in their 50s, including 26 males and 29 females. Each subject received 12 sessions of stimulation over a one-month period. In each session, low-frequency electrical stimulation at an average of 24 µA and 2 Hz was applied to the acupuncture points BL62 and KI6, and event-related potentials (ERPs) were measured before the first session and after the last session of the electrical stimulation. RESULTS: The results of a chi-square test indicated that the double-blind test was conducted correctly. Compared to the Sham group, all the subjects in the Real stimulation group showed a tendency toward a decreasing P300 latency and increasing P300 amplitude after all 12 sessions of stimulation. In the women, the amplitude significantly increased at Fz, Fcz, Cz, Cpz, and Pz. CONCLUSIONS: With this experiment, the low-frequency electrical stimulation of two acupuncture points (BL62 and K16) was confirmed to have a positive influence on the prevention of natural cerebral aging. TRIAL REGISTRATION: This study was registered at the Clinical Research Information Service (CRIS) of the National Research Institute of Health ( https://cris.nih.go.kr/cris/search/search_result_st01_en.jsp? , Registration Number: KCT0001940). The date of registration was June 9, 2016.

Case report: fainting during acupuncture stimulation at acupuncture point LI4.

BACKGROUND: Fainting is one of the major adverse events that can occur as a result of acupuncture treatment. However, the observation of changes in biological parameters is rarely available when fainting occurs. In this case report, we could observe changes in the electroencephalogram (EEG) in a participant who fainted while participating in a clinical trial aiming to observe a relationship between acupuncture stimulation at LI4 acupuncture point and EEG in healthy adults. CASE PRESENTATION: The EEG pattern of participant changed twice. The first change was in response to the acupuncture needle insertion, and the second change occurred during fainting. Both changes consisted of a burst in EEG amplitude, but the pattern of details was different. Multiple areas of the cortex were activated, and the increased ratio of the γ wave was not observed during fainting. While acupuncture needle insertion, only the sensory cortex were activated and increased the ratio of the γ wave. CONCLUSIONS: This single case is presented to improve the understanding of fainting during acupuncture as an adverse event and to explore the mechanism of acupuncture treatment, despite the absence of statistics and repeatability. This information can provide a new viewpoint about the mechanism of acupuncture treatment and the possibility of new techniques based on acupuncture.

Secretory factors of human chorion-derived stem cells enhance activation of human fibroblasts.

BACKGROUND AIMS: Wound healing remains a principal challenge in modern medical science. Chorion-dervied stem cells (CDSCs), isolated from human placenta, have largely been overlooked, and few studies on their potential in wound healing have been conducted. In this study, we investigated the functional characteristics of CDSCs compared with adipose-derived stem cells (ASCs) on human fibroblasts (HFs). METHODS: We analyzed CDSCs by means of flow cytometry to confirm their mesenchymal stromal cell characteristics. We then evaluated the paracrine effects of CDSCs on HFs in a co-culture system and focused on fibroblast proliferation, migration and collagen synthesis. To explore the potential of CDSCs in wound healing, CDSC- and ASC-secreted factors were compared by use of a cytokine antibody array. RESULTS: CDSCs had morphology similar to MSCs and expressed a mesenchymal stromal cell phenotype. HF proliferation and migration increased more than 5-fold when co-cultured with CDSCs. Furthermore, Western blot and reverse transcription-polymerase chain reaction analysis showed that expression of collagen (types I and III) in fibroblasts was upregulated 2-fold when co-cultured with CDSCs. Cytokine array results of CDSC-conditioned medium and ASC-conditioned medium revealed the presence of growth factors known to influence wound healing, including interleukin -6, interleukin -8, monocyte chemotactic protein 1 and regulated on activation, normal T cells expressed and secreted. CONCLUSIONS: Our data demonstrated that CDSCs are functionally similar to ASCs, promote HF activation, and secrete growth factors that influence wound healing. Therefore, we suggest that CDSCs are potentially applicable in wound healing.

Involvement of reactive oxygen species in cocaine-taking behaviors in rats.

Reactive oxygen species (ROS) have been implicated in the development of behavioral sensitization following repeated cocaine exposure. We hypothesized that increased ROS following cocaine exposure would act as signaling molecules in the mesolimbic dopamine (DA) system, which might play an important role in mediating the reinforcing effects of cocaine. The aim of this study was to evaluate cocaine enhancement of brain metabolic activity and the effects of ROS scavengers on cocaine self-administration behavior, cocaine-induced ROS production in the nucleus accumbens (NAc) and cocaine enhancement of DA release in the NAc. Metabolic neural activity monitored by temperature and oxidative stress were increased in NAc following cocaine exposure. Systemic administration of the ROS scavenger N-tert-butyl-α-phenylnitrone (PBN) or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), either pre- or post-treatment, significantly decreased cocaine self-administration without affecting food intake. Infusion of TEMPOL into the NAc inhibited cocaine self-administration. Increased oxidative stress was found mainly on neurons, but not astrocytes, microglia or oligodendrocytes, in NAc of rats self-administering cocaine. TEMPOL significantly attenuated cocaine-induced enhancement of DA release in the NAc, compared to saline controls. TEMPOL had no effect on the enhancement of DA release produced by the DA transporter inhibitor GBR12909. Taken together, these findings suggest that enhancement of ROS production in NAc neurons contributes to the reinforcing effect of cocaine.

The stem cell potential and multipotency of human adipose tissue-derived stem cells vary by cell donor and are different from those of other types of stem cells.

Human adipose tissue-derived mesenchymal stem cells (AT-MSCs) from various sites are applied in tissue engineering and cell therapy. The condition of AT-MSCs depends on the donor's age, body mass index (BMI), and gender. AT-MSCs from 66 human donors were analyzed, and the cells were sorted according to donor age (10-19 years: n = 1; 20-29 years: n = 5; 30-39 years: n = 12; 40-49 years: n = 22; 50-59 years: n = 12; 60-69 years: n = 9, and 70 years or older: n = 5), BMI (under 25, 25-30, and over 30), and gender (19 males and 48 females). Additionally, AT-MSCs were compared to bone marrow MSCs and chorionic tissue-derived MSCs. We measured the MSC yield, growth rate, colony-forming units, multipotency, and surface antigens. AT-MSC proliferation was greater in cells isolated from individuals aged less than 30 years compared to the proliferation of AT-MSCs from those over 50 years old. BMI was correlated with osteogenic differentiation potency; increased BMI enhanced osteogenesis. Adipogenic differentiation was more strongly induced in cells isolated from donors aged less than 30 years compared to those isolated from other age groups. Also, a BMI above 30 was associated with enhanced adipogenic differentiation compared to cells isolated from individuals with a BMI below 25. Bone marrow MSCs were strongly induced to differentiate along both osteogenic and adipogenic lineages, whereas AT-MSCs predominantly differentiated into the chondrogenic lineage. Therefore, the type of regeneration required and variations among potential donors must be carefully considered when selecting MSCs for use in applied tissue engineering or cell therapy.

Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study.

BACKGROUND: In this study, we explored the potential of human adipose tissue-derived extracellular matrix (adECM) sheets augmented with crosslinked hyaluronic acid (HA) as advanced wound dressings. We aimed to enhance healing efficacy while optimizing cost efficiency. METHODS: The adECM was processed from healthy donor tissue and combined with crosslinked HA to form ECM-HA sheets (Scaffiller, Medikan, Korea). In vitro experiments involved seeding adipose-derived stem cells (ASCs) onto these sheets and assessing cell survival and cytokine production. In vivo testing utilized a rat wound model, comparing ECM-HA sheet with HA-based dressing and polyurethane foam dressing. Re-epithelialization and collagen deposition were examined through histopathological examinations, whereas immunohistochemistry was used to assess CD31, alpha smooth muscle actin (α-SMA), and Tenascin C expression as contributing factors to wound healing. RESULTS: Results indicated that ECM-HA sheets were produced efficiently, with enhanced growth factor production and ASC survival observed in vitro. In vivo, ECM-HA sheets demonstrated accelerated wound healing, evidenced by improved epithelialization, thicker dermis, increased collagen deposition, and enhanced vascularity. Notably, they exhibited reduced myofibroblast activity and increased expression of Tenascin C, suggesting a favorable healing environment. CONCLUSION: ECM-HA sheets offer a promising approach for wound management, combining the benefits of adECM and HA. They present improved stability and cost-effectiveness while promoting essential aspects of wound healing such as angiogenesis and collagen formation. This study underscores the therapeutic potential of ECM-HA sheets in clinical applications aimed at facilitating wound repair.

Vessel-Derived Decellularized Extracellular Matrices (VdECM): Novel Bio-Engineered Materials for the Wound Healing.

BACKGROUND: Decellularized extracellular matrix (dECM) is a non-cellular scaffold with various functions in tissue engineering and regenerative medicine. Elastin is related to tissue elasticity and scarless wound healing, abundantly found in lung and blood vessel tissues. We studied the characteristics of blood vessel-derived dECM (VdECM) and its effect in wound healing. METHODS: VdECM was prepared from porcine blood vessel tissue. Weight percentages of elastin of VdECM and atelocollagen were analyzed. Migratory potential of VdECM was tested by scratch assay. VdECM in hydrogel form was microscopically examined, tested for fibroblast proliferation, and examined for L/D staining. Cytokine array of various growth factors in adipocyte-derived mesenchymal stem cell (ASC) media with VdECM was done. Animal wound model showed the wound healing effect of VdECM hydrogel in comparison to other topical agents. RESULTS: VdECM contained 6.7 times more elastin than atelocollagen per unit weight. Microscopic view of 0.35% VdECM hydrogel showed consistent distribution. Compared to 3% atelocollagen, 0.35% VdECM showed superior results in fibroblast migration. Fluorescent microscopic findings of L/D assay had highest percentage of cell survival in 1% VdECM compared to atelocollagen. Growth factor expression was drastically amplified when VdECM was added to ASC media. In the animal study model, epithelialization rate in the VdECM group was higher than that of control, oxytetracycline, and epidermal growth factor ointments. CONCLUSION: VdECM contains a high ratio of elastin to collagen and amplifies expressions of many growth factors. It promotes fibroblast migration, proliferation, and survival, and epithelialization comparable to other topical agents.

Mathematical Distinction in Action Potential between Primo-Vessels and Smooth Muscle.

We studied the action potential of Primo-vessels in rats to determine the electrophysiological characteristics of these structures. We introduced a mathematical analysis method, a normalized Fourier transform that displays the sine and cosine components separately, to compare the action potentials of Primo-vessels with those for the smooth muscle. We found that Primo-vessels generated two types of action potential pulses that differed from those of smooth muscle: (1) Type I pulse had rapid depolarizing and repolarizing phases, and (2) Type II pulse had a rapid depolarizing phase and a gradually slowing repolarizing phase.

Exploration of new electroacupuncture needle material.

Background. Electro Acupuncture (EA) uses the acupuncture needle as an electrode to apply low-frequency stimulation. For its safe operation, it is essential to prevent any corrosion of the acupuncture needle. Objective. The aim of this study is to find an available material and determine the possibility of producing a standard EA needle that is biocompatible. Methods. Biocompatibility was tested by an MTT assay and cytotoxicity testing. Corrosion was observed with a scanning electron microscope (SEM) after 0.5 mA, 60 min stimulation. The straightness was measured using a gap length of 100 mm, and tensile testing was performed by imposing a maximum tensile load. Results. Phosphor bronze, Ni coated SS304, were deemed inappropriate materials because of mild-to-moderate cytotoxicity and corrosion. Ti-6Al-4V and SS316 showed no cytotoxicity or corrosion. Ti-6Al-4V has a 70 times higher cost and 2.5 times lower conductivity than SS316. The results of both straightness and tensile testing confirmed that SS316 can be manufactured as a standard product. Conclusion. As a result, we confirmed that SS316 can be used a new EA electrode material. We hope that a further study of the maximum capacity of low-frequency stimulation using an SS316 for safe operation.

Bone Regeneration with 3D-Printed Hybrid Bone Scaffolds in a Canine Radial Bone Defect Model.

BACKGROUND: The repair of large bone defects remains a significant challenge in clinical practice and requires bone grafts or substitute materials. In this study, we developed a unique hybrid bone scaffold comprising a three dimensional (3D)-printed metal plate for weight bearing and a biodegradable polymer tube serving as bone conduit. We assessed the long-term effect of the hybrid bone scaffold in repairing radial bone defects in a beagle model. METHODS: Bone defects were created surgically on the radial bone of three beagle dogs and individually-tailored scaffolds were used for reconstruction with or without injection of autologous bone and decellularized extracellular matrix (dECM). The repaired tissue was evaluated by X-ray, micro-computed tomography, and histological observation 6 months after surgery. The functional integrity of hybrid bone scaffold-mediated reconstructions was assessed by gait analysis. RESULTS: In vivo analysis showed that the hybrid bone scaffolds maintained the physical space and bone conductivity around the defect. New bone was formed adjacent to the scaffolds. Addition of autologous bone and dECM in the polymer tube improved healing by enhancing bone induction and osteoconduction. Furthermore, the beagles' gait appeared normal by 4 months. CONCLUSION: The future of bone healing and regeneration is closely related to advances in tissue engineering. Bone production using autologous bone and dECM loaded on 3D-printed hybrid bone scaffolds can successfully induce osteogenesis and provide mechanical force for functional bone regeneration, even in large bone defects.

Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats.

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR.

The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis.

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.

A Novel Hypothesis and Characterization to Isolate Microvascular Endothelial Cells Simultaneously with Adipose-Derived Stem Cells from the Human Adipose-Derived Stromal Vascular Fraction.

BACKGROUND: Angiogenesis and vasculogenesis are essential processes for successful tissue regeneration in tissue engineering and regenerative medicine. The adipose-derived stromal vascular fraction (SVF) is not only a source of adipose stem cells (ASC) but also a suitable source of microvascular endothelial cells because it is a rich capillary network. So, we propose a new hypothesis for isolating adipose-derived human microvascular endothelial cells (HMVEC-A) from the SVF and developed a dual isolation system that isolates two cell types from one tissue. METHOD: To isolate HMVEC-A, we analyzed the supernatant discarded when ASC is isolated from the adipose-derived SVF. Based on this analysis, we assumed that the SVF adherent to the bottom of the culture plate was divided into two fractions: the stromal fraction as the ASC-rich fraction, and the vascular fraction (VF) as the endothelial cells-rich fraction floating in the culture supernatant. VF isolation was optimized and the efficiency was compared, and the endothelial cells characteristics of HMVEC-A were confirmed by flow cytometric analysis, immunocytochemistry (ICC), a DiI-acetylated low-density lipoprotein (DiI-Ac-LDL) uptake, and in vitro tube formation assay. RESULTS: Consistent with the hypothesis, we found a large population of HMVEC-A in the VF and isolated these HMVEC-A by our isolation method. Additionally, this method had higher yields and shorter doubling times than other endothelial cells isolation methods and showed typical morphological and phenotypic characteristics of endothelial cells. CONCLUSION: Cells obtained by the method according to our hypothesis can be applied as a useful source for studies such as tissue-to-tissue networks, angiogenesis and tissue regeneration, patient-specific cell therapy, and organoid chips.

Flexible Adipose-Vascular Tissue Assembly Using Combinational 3D Printing for Volume-Stable Soft Tissue Reconstruction.

A new concept, assembling cell-laden tissue modules, is for the first time proposed for soft tissue engineering. Adipose-vascular tissue modules composed of a synthetic polymer-based substructure and customized bioinks using planar 3D cell printing are engineered. Such tissue modules are systematically assembled into a synthetic polymer-based module holder fabricated with rotational 3D printing, resulting in the development of a flexible and volumetric tissue assembly. Whereas most of the previous studies about the construction of adipose tissue are limited to hypoxia, poor vascularization, rapid resorption, and mismatch in mechanical properties, it is aimed to realize the construction of nonhypoxic, flexible, and volume-stable tissue assembly in this study. The significance of engineered tissue assembly is proven through various in vitro and in vivo evaluations. In particular, stable volume and remarkable neovascularization/adipogenesis are observed in the implanted assembly over four weeks. Interestingly, the size of newly formed lipid droplets and the remodeled morphology in the assembly are comparable to those in native adipose tissue. As far as it is known, this work is a first report suggesting a cell printing-based tissue assembly for functional reconstruction of soft tissue.

Optimal Condition of Isolation from an Adipose Tissue-Derived Stromal Vascular Fraction for the Development of Automated Systems.

BACKGROUND: The stromal vascular fraction (SVF) isolated from adipose tissue, which contains stem cells as well as other cell types, has been applied in various research fields. Although different enzymatic concentrations and treatment durations have been applied to isolate the SVF, optimal conditions have not been established. Thus, we aimed to establish the optimal conditions for isolation of the SVF from adipose tissue by automated systems. METHODS: The SVF was collected from removed adipose tissues of five donors during surgery. The SVF was treated with 0.1% or 0.2% collagenase type I for 20, 40, or 60 min. Then, colony forming unit (CFU) assays and flow cytometry were performed to characterize the adipose stem cells (ASCs). A cytokine array was used to investigate the correlation between colony-formation ability and the secretion of isolated ASCs. RESULTS: Treatment with 0.1% collagenase type I for 60 min resulted in a higher SVF yield, whereas treatment with 0.1% collagenase for 40 min resulted in higher CFU values. In addition, expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 in the SVF was higher in the high-CFU group than in the low-CFU group. CONCLUSION: The optimal conditions for isolation of the SVF from adipose tissue were treatment with 0.1% collagenase type I for 40 min. We identified the conditions required for efficient SVF isolation based on high CFU values, and our results will facilitate the development of automated systems.

Acupuncture attenuates alcohol dependence through activation of endorphinergic input to the nucleus accumbens from the arcuate nucleus.

A withdrawal-associated impairment in ß-endorphin neurotransmission in the arcuate nucleus (ARC) of the hypothalamus is associated with alcohol dependence characterized by a chronic relapsing disorder. Although acupuncture activates ß-endorphin neurons in the ARC projecting to the nucleus accumbens (NAc), a role for ARC ß-endorphin neurons in alcohol dependence and acupuncture effects has not been examined. Here, we show that acupuncture at Shenmen (HT7) points attenuates behavioral manifestation of alcohol dependence by activating endorphinergic input to the NAc from the ARC. Acupuncture attenuated ethanol withdrawal tremor, anxiety-like behaviors, and ethanol self-administration in ethanol-dependent rats, which are mimicked by local injection of ß-endorphin into the NAc. Acupuncture also reversed the decreased ß-endorphin levels in the NAc and a reduction of neuronal activity in the ARC during ethanol withdrawal. These results suggest that acupuncture may provide a novel, potential treatment strategy for alcohol use disorder by direct activation of the brain pathway.

Adipose Stem Cells with Conditioned Media for Treatment of Acne Vulgaris Scar.

This study was to investigate the effect of subcutaneous injection of the adipose stem cells (ASCs) with conditioned media (CM) in the treatment of acne vulgaris scar. We used Adult male New Zealand white rabbit ears as an animal model and induced acne formation by Kignman method. Adipose tissue was isolated and harvested from the scapula of rabbits, and ASCs were cultured and expanded until passage 1. There have four groups in our experiment, include phosphate buffered saline (PBS), ASCs with PBS (ASC + PBS), CM, and ASCs with CM (ASC + CM) group. This solution of 0.6 ml injected to subcutaneous in each group. ASC + PBS and ASC + CM groups were containing ASCs of 5.0 × 106 cells/ml. We analyzed the treatment of 4 groups to scar tissue after 2 and 4 weeks by hematoxylin and eosin stain, immunohistochemistry, and RNA expression level of tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), and matrix metalloproteinase-2 (MMP-2). Also, the expression of keratin 16 (K16) was detected by western blot analysis. H&E stain showed that infiltration of inflammation cells was significantly reduced at 2 and 4 weeks, as well as re-epithelialization was improved in the ASC + CM group. The ASC + CM gourp was reduced both expression levels of TNF-α, IL-1α, and MMP-2 and K16 protein level. In conclusion, the ASCs with CM has a significant curative effect on acne vulgaris scar, more to the point, the CM has a key role on treatment. It could be applied to a therapeutic approach to regenerate to treat acne vulgaris scar.