Understanding the Effects of Non-Invasive Transauricular Vagus Nerve Stimulation On EEG and HRV.

Several studies have demonstrated promising results of transcutaneous auricular vagus nerve stimulation (taVNS) in treating various disorders; however, no mechanistic studies have investigated this technique's neural network and autonomic nervous system effects. This study aims to describe how taVNS can affect EEG metrics, HRV, and pain levels. Healthy subjects were randomly allocated into two groups: the active taVNS group and the sham taVNS group. Electroencephalography (EEG) and Heart Rate Variability (HRV) were recorded at baseline, 30 min, and after 60 min of 30 Hz, 200-250 µs taVNS, or sham stimulation, and the differences between the metrics were calculated. Regarding vagal projections, some studies have demonstrated the role of the vagus nerve in modulating brain activity, the autonomic system, and pain pathways. However, more data is still needed to understand the mechanisms of taVNS on these systems. In this context, this study presents methods to provide data for a deeper discussion about the physiological impacts of this technique, which can help future therapeutic investigations in various conditions.

Understanding the Neuroplastic Effects of Auricular Vagus Nerve Stimulation in Animal Models of Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Transauricular vagus nerve stimulation (taVNS) is being studied as a feasible intervention for stroke, but the mechanisms by which this non-invasive technique acts in the cortex are still broadly unknown. OBJECTIVES: This study aimed to systematically review the current pre-clinical evidence in the auricular vagus nerve stimulation (aVNS) neuroplastic effects in stroke. METHODS: We searched, in December of 2022, in Medline, Cochrane, Embase, and Lilacs databases. The authors executed the extraction of the data on Excel. The risk of bias was evaluated by adapted Cochrane Collaboration's tool for animal studies (SYRCLES's RoB tool). RESULTS: A total of 8 studies published between 2015 and 2022 were included in this review, including 391 animal models. In general, aVNS demonstrated a reduction in neurological deficits (SMD = -1.97, 95% CI -2.57 to -1.36, I2 = 44%), in time to perform the adhesive removal test (SMD = -2.26, 95% CI -4.45 to -0.08, I2 = 81%), and infarct size (SMD = -1.51, 95% CI -2.42 to -0.60, I2 = 58%). Regarding the neuroplasticity markers, aVNS showed to increase microcapillary density, CD31 proliferation, and BDNF protein levels and RNA expression. CONCLUSIONS: The studies analyzed show a trend of results that demonstrate a significant effect of the auricular vagal nerve stimulation in stroke animal models. Although the aggregated results show high heterogeneity and high risk of bias. More studies are needed to create solid conclusions.

Screening fundus photography predicts and reveals risk factors for glaucoma conversion in eyes with large optic disc cupping.

This study aimed to investigate the risk factors for glaucoma conversion and progression in eyes with large optic disc cupping without retinal nerve fiber layer defect (RNFLD). Five hundred forty-two eyes of 271 subjects who had a vertical cup-to-disc ratio (CDR) ≥ 0.6 without RNFLD were enrolled. Characteristics for optic disc configuration (including CDR, vertical cupping, ISNT rule, disc ovality, peripapillary atrophy [PPA]-to-disc area [DA] ratio, and lamina cribrosa pore visibility) and blood vessels (including central retinal vessel trunk [CRVT] nasalization, bayoneting of vessels, baring of circumlinear vessels, history of disc hemorrhage [DH] and vessel narrowing/sclerotic change) were evaluated. From a median follow-up of 11.3 years, 26.6% of eyes (n = 144) developed RNFLD within a median of 5.1 years. Baseline factors, including vertical CDR ≥ 0.7 (hazard ratio [HR] = 2.12), vertical cupping (HR = 1.93), ISNT rule violation (HR = 2.84), disc ovality ≥ 1.2 (HR = 1.61), PPA-to-DA ratio ≥ 0.4 (HR = 1.77), CRVT nasalization ≥ 60% (HR = 1.77), vessel narrowing/sclerotic change (HR = 2.13), DH history (HR = 5.60), and baseline intraocular pressure ≥ 14 mmHg (HR = 1.70) were significantly associated with glaucoma conversion (all Ps < 0.05). An HR-matched scoring system based on initial fundus photography predicted glaucoma conversion with specificity of 90.4%. Careful examination of the optic nerve head and vascular structures can help to predict the risk of glaucoma conversion in eyes with large optic disc cupping.

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis.

Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.

Diagnostic Roots Radiofrequency Sensory Stimulation Looking for Symptomatic Injured Roots in Multiple Lumbar Stenosis.

Objective: We present how to perform radiofrequency sensory stimulation (RFSS) and whether RFSS could be helpful in identifying symptomatic injured roots in multilevel lumbar stenosis. Methods: Consecutive patients who underwent RFSS from 2010 to 2012 were enrolled. To identify pathologic lesions, RFSS was performed for suspicious roots, as determined using lumbar magnetic resonance imaging (MRI). The RFSS procedure resembled transforaminal root block. During RFSS of the suspicious root, patients could indicate whether stimulation induced their usual pain and/or sensory changes and could indicate whether the same leg area was affected. The number of possible symptomatic roots on MRI was evaluated before and after RFSS. Based on the RFSS results, we confirmed the presence of symptomatic nerve root(s) and performed surgical decompression. Surgical results, such as numeric rating scale (NRS) scores for low back pain (LBP) and leg pain (LP), and Oswestry disability index (ODI), were evaluated. Results: Ten patients were enrolled in the study. Their mean age was 70.1±9.7 years. Clinically, NRS-LBP, NRS-LP, and ODI before surgery were 5.1%, 7.5%, and 53.2%, respectively. The mean number of suspicious roots was 2.6±0.8. After RFSS, the mean number of symptomatic roots was 1.6±1.0. On average, 1.4 lumbar segments were decompressed. The follow-up period was 35.3±12.8 months. At the last follow-up, NRS-LBP, NRS-LP, and ODI were 3.1%, 1.5%, and 35.3%, respectively. There was no recurrence or need for further surgical treatment for lumbar stenosis. Conclusion: RFSS is a potentially helpful diagnostic tool for verifying and localizing symptomatic injured root lesions, particularly in patients with multilevel spinal stenosis.

Enhancing oxidative stability of tocopherol-enriched edible oils using short-term exposure to microwave irradiation.

The effect of microwave irradiation on the oxidative stability of tocopherol-enriched corn oil at temperatures of 60 or 100°C was evaluated using the Rancimat assay. Short durations of microwave treatment (1 min) on 10-g oil aliquots were found to increase the induction period of corn oil samples containing 500 and 1000 ppm tocopherol by 7.7% and 9.9%, respectively compared to control oils. The moisture content of tocopherol-enriched corn oil decreased by 15% compared to that of corn oil after 1 min of microwave treatment. At 100°C, 1000 ppm tocopherol-enriched corn oil received 3 min of microwave treatment had 5.8% and 9.9% lower primary and secondary oxidation products than control groups, respectively while this effect was not clearly observed for oils stored at 60°C. However, 15 min of microwave irradiation accelerated the rates of lipid oxidation in corn oils irrespective of the addition of tocopherol. Content of α- and γ-tocopherols in 1 min of microwave irradiated samples remained more by 28.8 and 5.8%, respectively than those of controls after 9 h heat treatment at 100°C. Overall, microwave irradiation within 3 min can increase the oxidative stability of 10 g-corn oils, especially at 100°C, which could be due to the reduced moisture content in the bulk oil matrix. Practical Application: A microwave oven is an irreplaceable home appliance and is widely used in households. Short time exposure to microwave irradiation can remove moisture efficiently from edible oils without the formation of oxidation products, which could increase the oxidative stability of these oils, especially under frying conditions. The results of this study can be utilized to ensure a longer shelf-life of fried products in the food industry by short time treatment of microwave irradiation.

Effects of photobiomodulation on annulus fibrosus cells derived from degenerative disc disease patients exposed to microvascular endothelial cells conditioned medium.

Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During this process, endothelial cells (ECs), which are primarily responsible for angiogenesis, interact with the adjacent annulus fibrosus (AF) cells, which are the first line of defence against the invasion of vascular structures into deeper IVD regions. However, the accumulation of inflammatory and catabolic enzymes that results from this interaction promotes matrix degradation and an inflammatory response. Thus, regulating the production of these mediators and catabolic enzymes could ameliorate IVD degeneration. Photobiomodulation (PBM) therapy is a non-invasive stimulation known to have biologically beneficial effects on wound healing, tissue repair, and inflammation. Here, we examined the effects of PBM, administered at various wavelengths (645, 525, and 465 nm) and doses (16, 32, and 64 J/cm2), on EC-stimulated human AF cells. Our results show that PBM selectively inhibited the EC-mediated production of inflammatory mediators, catabolic enzymes, and neurotrophins by human AF cells in a dose- and wavelength-dependent manner. These results suggest that PBM could be a superior and advanced treatment strategy for IVD degeneration.

Signaling pathway and structural features of macrophage-activating pectic polysaccharide from Korean citrus, Cheongkyool peels.

To characterize the immuno-stimulating ingredient from the Korean citrus, Cheongkyool, a crude polysaccharide (CCE-0) was isolated from the pectinase digests of Cheongkyool peels, from which the complex polysaccharide CCE-I was purified to homogeneity by gel filtration. CCE-I highly enhanced the production of IL-6, TNF-α, and NO in RAW 264.7 cell lines. It augmented the mRNA expression of IL-6, TNF-α, and iNOS in a dose-dependent manner. Moreover, CCE-I dose-dependently induced phosphorylation of MAPKs and NF-κB related proteins and led to the nuclear translocation of p65. The effect of CCE-I on NO and IL-6 production was suppressed by treatment with specific antibodies for TLR2, TLR4, and scavenger receptors. Conversely, the primary structure of CCE-I that exhibited potent immunostimulatory activity was characterized by sugar composition, linkage analysis, and oligosaccharide analysis after ß-elimination. The results suggested that CCE-I may be a rhamnogalacturonan-I type, highly branched polysaccharide with short arabinan and galactan side chains.

Rhamnogalacturonan-I-Type Polysaccharide Purified from Broccoli Exerts Anti-Metastatic Activities Via Innate Immune Cell Activation.

To examine the anti-metastatic activities of polysaccharides in broccoli, purified polysaccharides (BCE-I, -II, and -III) were isolated by fractionation of broccoli enzyme extracts and subsequent ethanol precipitation. BCE-I mainly consisted of galactose and arabinose, whereas BCE-II mainly consisted of galacturonic acid and rhamnose, and BCE-III mainly consisted of rhamnose and galactose. Of the three fractions, stimulation of murine peritoneal macrophages by BCE-I showed the greatest enhancement of tumor necrosis factor-α, interleukin (IL)-12, and IL-6 secretion. In addition, intravenous (i.v.) administration of BCE-I enhanced the lethal activity of natural killer (NK) cells on YAC-1 tumor cells significantly and dose-dependently in an ex vivo experiment of NK cell activity. In an experimental model using lung metastasis of Colon26-M3.1 carcinoma cells, prophylactic i.v. and oral administration of BCE-I significantly and dose-dependently inhibited lung metastatic activity. Furthermore, the inhibitory activity of BCE-1 on lung metastasis partially disappeared when NK cell function was removed through treatment of rabbit anti-asialo GM1. These results indicated that BCE-I has potent antitumor metastatic activity, and that its anti-metastatic activity has relevance to the stimulation of NK and other immune cells.

Increased heat shock protein 70 expression attenuates pancreatic fibrosis induced by dibutyltin dichloride.

OBJECTIVES: Heat shock protein (HSP) 70 performs a chaperoning function and protects cells against injury. Although the effect of HSPs against acute inflammatory change has been proven, the relationship between HSP70 and chronic pancreatitis remains unclear. This study aimed to investigate the protective effect of increased HSP70 expression induced by thermal stress against pancreatic fibrosis in experimental chronic pancreatitis. MATERIALS AND METHODS: Two experiments to evaluate pancreatic HSP70 expression induced by thermal stress and determine the effect of increased HSP70 expression against pancreatic fibrosis were performed. To investigate HSP70 expression, rats were immersed in a warm bath and sequentially killed, and pancreatic HSP70 expression was measured. To study the effect of increased HSP70 expression, pancreatic fibrosis was induced by intravenous injection of dibutyltin dichloride (DBTC) and analyzed under repeated thermal stress. The severity of pancreatic fibrosis was measured. RESULTS: Thermal stress significantly increased HSP70 expression in the pancreas. HSP70 expression peaked at 6-12 h after warm bathing, and the increased HSP70 expression was associated with the attenuation of pancreatic fibrosis. Although pancreatic fibrosis was induced by DBTC injection, HSP70 expression induced by repeated thermal stress diminished the severity of atrophy and fibrosis. On western blot analysis, collagen type 1 expression was diminished in the increased HSP70 expression group, but not α-smooth muscle actin expression. CONCLUSIONS: Thermal stress could increase pancreatic HSP70 expression, and induced HSP70 expression showed a protective effect against pancreatic fibrosis. Modulation of HSP70 expression could be a potential therapeutic target in the treatment of chronic pancreatitis.

Photobiomodulation of extracellular matrix enzymes in human nucleus pulposus cells as a potential treatment for intervertebral disk degeneration.

Intervertebral disc (IVD) degeneration is associated with imbalances between catabolic and anabolic responses, regulated by extracellular matrix (ECM)-modifying enzymes such as matrix metalloproteinases (MMPs) and their endogenous tissue inhibitors of metalloproteinases (TIMPs). Potential contributing factors, such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, derived from infiltrated, activated macrophages within IVD tissues, can trigger abnormal production of ECM-modifying enzymes and progression of IVD degeneration. Novel therapies for regulating ECM-modifying enzymes can prevent or ameliorate IVD degeneration. Photobiomodulation (PBM), known to regulate wound repair, exhibits regenerative potential by modulating biological molecules. This study examined the effects of PBM, administered at various wavelengths (630, 525, and 465 nm) and energy densities (16, 32, and 64 J/cm2), on the production of ECM-modifying enzymes in replicated degenerative IVD. Our results showed that PBM selectively inhibited the production of ECM-modifying enzymes in a dose- and wavelength-dependent manner, suggesting that it could be a novel tool for treating symptomatic IVD degeneration.

Phototherapy suppresses inflammation in human nucleus pulposus cells for intervertebral disc degeneration.

The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells. Human NP cells were treated with soluble factors derived from macrophages in an inflammatory microenvironment, similar to that found in degenerative IVD. Human NP cells were also treated with phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2), and their cytokine and chemokine levels were detected. The soluble factors caused modulated expression of IL-6, IL-8, and matrix metalloproteinases (MMPs) at the gene and protein levels, causing a shift toward matrix catabolism through the expression of MMPs and increased pain-related factors via preferential activation of the nuclear factor-kappa B (NF-κB) p50 protein. Importantly, phototherapy attenuated the protein and gene expression of pain-related factor IL-6 at all doses and wavelengths. Interestingly, phototherapy also modulated the protein and gene expression of IL-8, which is responsible for the anabolic response, at a wavelength of 465 nm at all doses, in human NP cells. These findings suggested that phototherapy, at an optimal dose and wavelength, might be a useful therapeutic tool to treat IVD degeneration.

Inhibitory effect of Gastrodia elata Blume extract on alpha-melanocyte stimulating hormone-induced melanogenesis in murine B16F10 melanoma.

BACKGROUND/OBJECTIVES: Gastrodia elata Blume (GEB), a traditional herbal medicine, has been used to treat a wide range of neurological disorders (e.g., paralysis and stroke) and skin problems (e.g., atopic dermatitis and eczema) in oriental medicine. This study was designed to investigate whether GEB extract inhibits melanogenesis activity in murine B16F10 melanoma. MATERIALS/METHOD: Murine B16F10 cells were treated with 0-5 mg/mL of GEB extract or 400 µg/mL arbutin (a positive control) for 72 h after treatment with/without 200 nM alpha-melanocyte stimulating hormone (α-MSH) for 24 h. Melanin concentration, tyrosinase activity, mRNA levels, and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (Trp)1, and Trp2 were analyzed in α-MSH-untreated and α-MSH-treated B16F10 cells. RESULTS: Treatment with 200 nM α-MSH induced almost 2-fold melanin synthesis and tyrosinase activity along with increased mRNA levels and protein expression of MITF, tyrosinase, Trp1 and Trp2. Irrespective of α-MSH stimulation, GEB extract at doses of 0.5-5 mg/mL inhibited all these markers for skin whitening in a dose-dependent manner. While lower doses (0.5-1 mg/mL) of GEB extract generally had a tendency to decrease melanogenesis, tyrosinase activity, and mRNA levels and protein expression of MITF, tyrosinase, Trp1, and Trp2, higher doses (2-5 mg/mL) significantly inhibited all these markers in α-MSH-treated B16F10 cells in a dose-dependent manner. These inhibitory effects of the GEB extract at higher concentrations were similar to those of 400 µg/mL arbutin, a well-known depigmenting agent. CONCLUSIONS: These results suggest that GEB displays dose-dependent inhibition of melanin synthesis through the suppression of tyrosinase activity as well as molecular levels of MITF, tyrosinase, Trp1, and Trp2 in murine B16F10 melanoma. Therefore, GEB may be an effective and natural skin-whitening agent for application in the cosmetic industry.

A Dalbergia odorifera extract improves the survival of endotoxemia model mice by inhibiting HMGB1 release.

BACKGROUND: Dalbergia odorifera T. Chen (Leguminosae) is an indigenous medicinal herb that is widely used as a popular remedy in northern and eastern Asia. However, the cellular mechanisms underlying the biological activity of D. odorifera are not fully elucidated. METHODS: Anti-inflammatory effect of D. odorifera extract (DOE) was determined through intraperitoneal injection in a mouse model of endotoxemia induced by lipopolysaccharide (LPS). RAW 264.7 cells, a murine macrophage, were also treated with LPS to generate a cellular model of inflammation, and investigated the anti-inflammatory activity and underlying mechanisms of DOE and its constituent isoliquiritigenin. RESULTS: DOE dose-dependently inhibited LPS-induced release of high mobility group box 1 (HMGB1), a late proinflammatory cytokine, and decreased cytosolic translocation of HMGB1 in RAW264.7 cells. This inhibitory effect of DOE on HMGB1 release was observed in cells treated with DOE before or after LPS treatment, suggesting that DOE is effective for both treatment and prevention. In addition, DOE significantly inhibited LPS-induced formation of nitric oxide (NO) and expression of inducible NO synthase (iNOS) in a dose-dependent manner. These effects of DOE were accompanied by suppression of HMGB1 release triggered by LPS, suggesting a possible mechanism by which DOE modulates HMGB1 release through NO signaling. Isoriquiritigenin, a constituent of DOE, also attenuated LPS-triggered NO formation and HMGB1 release in RAW264.7 cells, indicating that isoriquiritigenin is an indexing molecule for the anti-inflammatory properties of DOE. Furthermore, c-Jun N-terminal kinase, but not extracellular signal-regulated kinase and p38, mediated DOE-dependent inhibition of HMGB1 release and NO/iNOS induction in RAW 264.7 cells exposed to LPS. Notably, administration of DOE ameliorated survival rates in a mouse model of endotoxemia induced by LPS, where decreased level of circulating HMGB1 was observed. CONCLUSION: These results suggest that DOE confers resistance to LPS-triggered inflammation through NO-mediated inhibitory effects on HMGB1 release.

Selenium Administration Attenuates 5-Flurouracil-Induced Intestinal Mucositis.

Chemotherapy-induced mucositis is mediated by the release of proinflammatory cytokines and reactive oxygen species. Selenium has several metabolic functions, including the protection of membrane lipids and macromolecules against oxidative damage. However, to date, there is little evidence on the effect of trace elements on intestinal mucositis after chemotherapy. This study investigated the protective effect of selenium against chemotherapy-induced mucositis in rats. Twenty-four 9-wk-old female Wistar rats were randomized to 4 groups: control, selenium, 5-fluorouracil (5-FU), and 5-FU plus selenium. Mucositis was induced by a single dose of 5-FU (400 mg/kg BW) via intraperitoneal injection, and selenium was administered by a single intraperitoneal dose of sodium selenite (0.2 mg/kg BW). Diarrhea and weight loss after 5-FU administration were attenuated by selenium treatment. The mean villus height in the 5-FU plus selenium group was significantly taller than rats administered with 5-FU alone, but not significantly different compared to the control group. Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α mRNA expression were significantly lower in the 5-FU plus selenium group than in the 5-FU only group (IL-1ß, P < 0.01; TNF-α, P < 0.05). These findings indicate that selenium protects the mucosa during chemotherapy via its anti-inflammatory effects and its suppression of cytotoxic cytokine production.

Gastrodia elata Blume Extract Modulates Antioxidant Activity and Ultraviolet A-Irradiated Skin Aging in Human Dermal Fibroblast Cells.

Gastrodia elata Blume (GEB), a traditional herbal medicine, has been used to treat a wide range of neurological disorders (e.g., paralysis and stroke) and skin problems (e.g., atopic dermatitis and eczema) in oriental medicine. This study was designed to investigate the antioxidant ability of GEB and its antiaging effect on human dermal fibroblast cells (HDF). The total phenolic and flavonoid contents of GEB were 21.8 and 0.43 mg/g dry weight (DW), respectively. The ergothioneine content of GEB was 0.41 mg/mL DW. The DPPH and ABTS radical scavenging activities of GEB at 5 and 10 mg/mL approximately ranged between 31% and 44%. The superoxide dismutase activity of GEB at 10 and 25 mg/mL was 57% and 76%, respectively. GEB increased procollagen type 1 (PC1) production and inhibited matrix metalloproteinase-1 (MMP-1) production and elastase-1 activity in UVA-irradiated HDF. PC1 messenger RNA (mRNA) levels decreased upon UVA irradiation, but recovered in response to high doses of GEB in HDF. On the contrary, GEB significantly decreased MMP-1 and elastase-1 mRNA levels, which were markedly induced in UVA-irradiated HDF. Collectively, these results suggest that GEB has sufficient antioxidant ability to prevent the signs of skin aging in UVA-irradiated human skin cells, suggesting its potential as a natural antiaging product.

Polyethylene glycol plus ascorbic acid for bowel preparation in chronic kidney disease.

The safety of polyethylene glycol plus ascorbic acid has not been fully investigated in patients with renal insufficiency. High-dose ascorbic acid could induce hyperoxaluria, thereby causing tubule-interstitial nephritis and renal failure. This study aims to evaluate the safety and efficacy of polyethylene glycol plus ascorbic acid in patients with chronic kidney disease.We retrospectively reviewed prospectively collected data on colonoscopy in patients with impaired renal function. Patients were divided into 2 groups: 2 L polyethylene glycol plus ascorbic acid (n = 61) and 4 L polyethylene glycol (n = 80). The safety of the 2 groups was compared by assessing the differences in laboratory findings before and after bowel cleansing.The laboratory findings were not significantly different before and after the administration of 2 L polyethylene glycol plus ascorbic acid or 4 L polyethylene glycol. In both groups, the estimated glomerular filtration rate was not influenced by the administration of the bowel-cleansing agent. Patients' reports on tolerance and acceptability were better in the 2 L polyethylene glycol plus ascorbic acid group than in the 4 L polyethylene glycol group.The 2 L polyethylene glycol plus ascorbic acid solution is a safe choice for bowel preparation before colonoscopy in patients with impaired renal function.

Bioconverted Jeju Hallabong tangor (Citrus kiyomi × ponkan) peel extracts by cytolase enhance antioxidant and anti-inflammatory capacity in RAW 264.7 cells.

BACKGROUND/OBJECTIVES: Citrus and its peels have been used in Asian folk medicine due to abundant flavonoids and usage of citrus peels, which are byproducts from juice and/or jam processing, may be a good strategy. Therefore, the aim of this study was to examine antioxidant and anti-inflammatory effects of bioconversion of Jeju Hallabong tangor (Citrus kiyomi × ponkan; CKP) peels with cytolase (CKP-C) in RAW 264.7 cells. MATERIALS/METHODS: Glycosides of CKP were converted into aglycosides with cytolase treatment. RAW 264.7 cells were pre-treated with 0, 100, or 200 µg/ml of citrus peel extracts for 4 h, followed by stimulation with 1 µg/ml lipopolysaccharide (LPS) for 8 h. Cell viability, DPPH radical scavenging activity, nitric oxide (NO), and prostagladin E2 (PGE2) production were examined. Real time-PCR and western immunoblotting assay were performed for detection of mRNA and/or protein expression of pro-inflammatory mediators and cytokines, respectively. RESULTS: HPLC analysis showed that treatment of CKP with cytolase resulted in decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycoside forms (naringenin and hesperetin). DPPH scavenging activities were observed in a dose-dependent manner for all of the citrus peel extracts and CKP-C was more potent than intact CKP. All of the citrus peel extracts decreased NO production by inducible nitric oxide synthase (iNOS) activity and PGE2 production by COX-2. Higher dose of CKP and all CKP-C groups significantly decreased mRNA and protein expression of LPS-stimulated iNOS. Only 200 µg/ml of CKP-C markedly decreased mRNA and protein expression of cyclooxygenase-2 in LPS-stimulated RAW 264.7 cells. Both 100 and 200 µg/ml of CKP-C notably inhibited mRNA levels of interleukin-1ß (IL-1ß) and IL-6, whereas 200 µg/ml CKP-C significantly inhibited mRNA levels of TNF-α. CONCLUSIONS: This result suggests that bioconversion of citrus peels with cytolase may enrich aglycoside flavanones of citrus peels and provide more potent functional food materials for prevention of chronic diseases attributable to oxidation and inflammation by increasing radical scavenging activity and suppressing pro-inflammatory mediators and cytokines.

Low level light therapy modulates inflammatory mediators secreted by human annulus fibrosus cells during intervertebral disc degeneration in vitro.

Intervertebral disc degeneration (IVD) is one of the important causes of low back pain and is associated with inflammation induced by interaction between macrophages and the human annulus fibrosus (AF) cells. Low-level light therapy (LLLT) has been widely known to regulate inflammatory reaction. However, the effect of LLLT on macrophage-mediated inflammation in the AF cells has not been studied till date. The aim of this study is to mimic the inflammatory microenvironment and to investigate the anti-inflammatory effect of LLLT at a range of wavelengths (405, 532 and 650 nm) on the AF treated with macrophage-like THP-1 cells conditioned medium (MCM) containing proinflammatory cytokines and chemokines (interleukin-1beta, tumor necrosis factor-alpha, interleukin-6 and 8). We observed that AF cells exposed to MCM secrete significantly higher concentrations of IL-6, IL-8, IL-1ß and TNF-α. LLLT markedly inhibited secretion of IL-6 at 405 nm in a time-dependent manner. Level of IL-8 was significantly decreased at all wavelengths in a time-dependent manner. We showed that MCM can induce the inflammatory microenvironment in AF cells and LLLT selectively suppressed IL-6 and 8 levels. The results indicate that LLLT is a potential method of IVD treatment and provide insights into further investigation of its anti-inflammation effect on IVD.

Antitumor metastasis activity of pectic polysaccharide purified from the peels of Korean Citrus Hallabong.

A polysaccharide fraction, HBE-III, was successfully purified in a high yield (40.4%) from its crude polysaccharide (HBE-0) which was prepared from pectinase hydrolysates of the peels of the Korean Citrus Hallabong. In experimental lung metastasis studies of Colon 26-M3.1 carcinoma cells, prophylactic administration of HBE-III significantly inhibited lung metastasis in a dose-dependent manner. In an in vitro cytotoxicity analysis, HBE-III (up to 1000 µg/mL) did not affect the growth of Colon 26-M3.1 cells and normal cells. HBE-III enhanced production of IL-6 and IL-12 by murine peritoneal macrophages. In an assay for natural killer (NK) cell activity, HBE-III (1000 µg/mouse, i.v.) significantly augmented NK cytotoxicity against Yac-1 tumor cells. The depletion of NK cells by injection of mouse anti-asialo GM1 serum abolished the inhibitory effect of HBE-III on lung metastasis of Colon 26-M3.1 cells. These data suggest that HBE-III may inhibit tumor metastasis via activation of macrophages and NK cells.