Pharmacopuncture Therapy as an Adjunctive Treatment for Patients with Lumbar Spinal Stenosis: A Pragmatic Randomized Controlled Pilot Trial.

Purpose: Pharmacopuncture therapy (PPT) combines medicinal extracts with acupuncture and is widely used as an adjunct in clinical practice. This study assessed the safety and feasibility of PPT in addition to conventional Korean Medicine treatment (CKMT), including electroacupuncture, cupping and infra-red, for lumbar spinal stenosis (LSS). Patients and Methods: Forty patients diagnosed with LSS were randomly assigned to undergo PPT with CKMT (experimental group) or CKMT alone (control group) at a 1:1 ratio, receiving 10 sessions of each intervention over five weeks. The primary clinical outcome was measured using the 100-mm Visual Analog Scale (VAS) for buttock and leg pain five weeks post-treatment. Secondary outcomes included clinically important difference (CID), Zurich Claudication Questionnaire, self-reported walking capacity, Modified-Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and the patient's global impression of change. The adverse events were assessed at each visit. The analysis of covariance was conducted to compare between two groups. Results: Intervention completion rates were 95% and 100% in the experimental and control groups, respectively. No statistically significant differences were found between groups regarding the primary outcome (adjusted mean difference: 8.0; 95% confidence interval: -1.4-17.4). The mean difference in the 100-mm VAS for low back pain at week 5 (adjusted mean difference: 12.9; 95% confidence interval: 2.4-23.4) and the proportion of patients who reached the minimum CID was higher in the experimental group than in the control group. However, no significant differences were observed with other secondary outcomes. One patient in the experimental group experienced a systemic skin rash that resolved the same day, whereas the adverse events in the other group were mild and transient. Conclusion: This trial demonstrated the feasibility of add-on effects and the safety of pharmacopuncture in patients with LSS. Further studies are warranted to evaluate the add-on effects of PPT in treating LSS. Trial Registration: Clinical Research Information Service (CRIS), KCT0007229; registered on April 26, 2022.

Effect and Safety of Combining Pharmacopuncture Therapy and Acupotomy in the Treatment of Patients with Degenerative Lumbar Spinal Stenosis: a Study Protocol for a Pragmatic, Assessor-Blinded, Randomized, Controlled Trial.

Background: : Pharmacopuncture therapy and acupotomy are commonly used in combination for Conventional Korean Medicine Treatments (CKMT) for the treatment of patients with lumbar spinal stenosis (LSS). The aim of this study is to evaluate the effect and safety of combining pharmacopuncture therapy and acupotomy in the treatment of LSS. Methods: : This study is designed as a pragmatic, assessor-blinded, randomized controlled trial with two parallel arms in a 1:1 ratio. A total of 104 participants diagnosed with LSS will be randomly assigned to an experimental group (pharmacopuncture therapy and acupotomy in addition to CKMT) or a control group (only CKMT). Patients in both groups will receive treatment two times weekly for 6 weeks. The primary outcome will be the mean change on the 100-mm visual analog scale (VAS) from the baseline to the end of the treatment (week 6). The secondary outcomes will include the mean change in the 100-mm VAS from baseline to week 10 and week 14, respectively. Proportion of patients who achieve the clinically important difference, Zurich Claudication Questionnaire, Roland-Morris disability questionnaire, self-reported maxium walking distance, EuroQol 5-dimension 5-level, and Patients' Global Impression of Change will also be assessed. Adverse events will be assessed at each visit. The outcomes will be measured for a total of 14 weeks, including a treatment period of 6 weeks and follow-up of 4, 8 weeks. Discussion: : The results of this trial will confirm the effect and safety of combining pharmacopuncture therapy and acupotomy in the treatment of patients with LSS.

Evaluating the efficacy of moving cupping for chronic low back pain using shear wave elastography: A parallel-arm, randomized controlled trial.

BACKGROUND: Chronic low back pain (CLBP) is a common condition that affects millions of people worldwide. Moving cupping has gained popularity as a complementary therapy for managing CLBP owing to its noninvasive and cost-effective nature. However, the lack of objective measures to assess its therapeutic effect has been a considerable challenge in evaluating the effectiveness of moving cupping for CLBP management. METHODS: We developed a randomized controlled trial (RCT) protocol for evaluating the effectiveness of a noninvasive treatment using moving cupping by assessing muscle relaxation with shear wave elastography (SWE). It involves the recruitment of 68 patients with CLBP and randomly assigns them to either the treatment or control group. The treatment group will receive moving cupping therapy for 2 weeks, while the control group will receive placebo treatment. It will utilize SWE to evaluate muscle relaxation at baseline, after 2 weeks of treatment, and 1 week after the end of treatment. Subjective reports of pain intensity and quality of life are also recorded at each time point. DISCUSSION: The protocol developed here utilizes SWE to objectively measure muscle stiffness, and coupled with moving cupping therapy, may be effective in conveying relative comparisons before and after treatment. Moving cupping therapy is expected to promote muscle relaxation and pain relief in patients with CLBP. This study has the potential to contribute to the development of objective measures for evaluating the therapeutic effects of traditional therapies and to provide valuable insight into their efficacy.

Preparation of Red Ginseng Marc-Derived Gintonin and Its Application as a Skin Nutrient.

Ginseng is one of the traditional herbal medicines for tonic. Gintonin is a new material derived from white/red ginseng and its lysophosphatidic acids (LPAs) play as a ligand for G protein-coupled LPA receptors. Korean red ginseng marc (KRGM) is a by-product after the KRG processes. We developed a low-cost/high-efficiency method for KRGM gintonin production. We further studied the KRGM gintonin-mediated anti-skin aging effects under UVB exposure using human dermal fibroblasts (HDFs). KRGM gintonin yield is about 8%. KRGM gintonin contains a high amount of LPA C18:2, lysophosphatidylcholine (LPC), and phosphatidylcholine (PC), which is similar to white ginseng gintonin. KRGM gintonin induced [Ca2+]i transient via LPA1/3 receptors and increased cell viability/proliferation under UVB exposure. The underlying mechanisms of these results are associated with the antioxidant action of KRGM gintonin. KRGM gintonin attenuated UVB-induced cell senescence by inhibiting cellular ß-galactosidase overexpression and facilitated wound healing. These results indicate that KRGM can be a novel bioresource of KRGM gintonin, which can be industrially utilized as new material for skin nutrition and/or skin healthcare.

Add-on Effect and Safety of Pharmacopuncture Therapy in the Treatment of Patients with Lumbar Spinal Stenosis.

Background: Recently, Korean Medicine treatment with pharmacopuncture therapy (PPT) has been increasingly used in clinical practice to improve symptoms in patients with lumbar spinal stenosis (LSS). The aim of this study is to evaluate the effectiveness and safety of PPT in addition to conventional Korean Medicine treatment (CKMT) for the treatment of patients with LSS, compared with CKMT alone. Methods: This study is designed as a pragmatic, randomized, two-armed, parallel, stratified (by sex), controlled pilot trial. Forty patients diagnosed with LSS will be randomly allocated to the PPT + CKMT group or the CKMT group. Patients in the two groups will receive treatment two times weekly for 5 weeks. The primary outcome will be the mean change in the 100-mm visual analog scale score from the baseline to the end of treatment (week 5). The secondary outcomes will include the clinically important difference, Zurich Claudication Questionnaire score, self-reported walking capacity, Modified-Modified Schober test, EuroQol 5-dimension 5-level questionnaire, and Patients' Global Impression of Change. Adverse events will be assessed at each visit. Discussion: The results of this study will provide meaningful data to evaluate the add-on effect and safety of PPT in the medical care of patients with LSS.

Manipulation of Unfrozen Water Retention for Enhancing Petroleum Hydrocarbon Biodegradation in Seasonally Freezing and Frozen Soil.

Manipulating the retention of unfrozen water in freezing contaminated soil to achieve prolonged bioremediation in cold climates remains unformulated. This freezing-induced biodegradation experiment shows how nutrient and zeolite amendments affect unfrozen water retention and hydrocarbon biodegradation in field-aged, petroleum-contaminated soils undergoing seasonal freezing. During soil freezing at a site-specific rate (4 to -10 °C and -0.2 °C/d), the effect of nutrients was predominant during early freezing (4 to -5 °C), alleviating the abrupt soil-freezing stress near the freezing-point depressions, elevating alkB1 gene-harboring populations, and enhancing hydrocarbon biodegradation. Subsequently, the effect of increased unfrozen water retention associated with added zeolite surface areas was critical in extending hydrocarbon biodegradation to the frozen phase (-5 to -10 °C). A series of soil-freezing characteristic curves with empirical α-values (soil-freezing index) were constructed for the tested soils and shown alongside representative curves for clays to sands, indicating correlations between α-values and nutrient concentrations (soil electrical conductivity), zeolite addition (surface area), and hydrocarbon biodegradation. Heavier hydrocarbons (F3: C16-C34) notably biodegraded in all treated soils (22-37% removal), as confirmed by biomarker-based analyses (17α(H),21ß(H)-hopane), whereas lighter hydrocarbons were not biodegraded. Below 0 °C, finer-grained soils (high α-values) can be biostimulated more readily than coarser-grained soils (low α-values).

Factors Associated with Molar-Incisor Hypomineralization: A Population-Based Case-Control Study.

Purpose: The purpose of this case-control study was to investigate the relationship between molar-incisor hypomineralization (MIH) and pre-, peri-, and postnatal conditions of children and mothers in South Korea. Methods: The Korean Academy of Pediatric Dentistry con- ducted this study to examine factors associated with MIH among six- to 13-year-olds. The European Academy of Pediatric Dentistry criteria and self-administered questionnaires associated with MIH were used. Results: In multivariable logistic regression analysis, the odds ratio (OR) of MIH for children whose mothers used health supplements during pregnancy was 0.65 (P=0.009). Also, children with more than three hours of out- door activities per day tended to have a lower MIH (P=0.03) than did those with zero hours of outdoor activity. Additionally, the OR of MIH for children whose mothers smoked during pregnancy was 2.37 (P=0.019) and the MIH found to be 1.33 times more frequent in children with respiratory infections during the first three years of life (P=0.048). Conclusions: Maternal smoking during pregnancy and child's pediatric respiratory infection suffered within three years after birth are factors associated with the MIH among Korean children. Further study is needed because the prevalence of MIH in children whose mothers taking health supplements (vitamins or folic acid or iron) during pregnancy is low.

Modified soil respiration model (URESP) extended to sub-zero temperatures for biostimulated petroleum hydrocarbon-contaminated sub-Arctic soils.

It has been increasingly reported that aerobic soil respiration activity (CO2 production and O2 consumption) is measurable in frozen cold-climate soils. This study modifies the Generalized Respiration (GRESP) model, a function of soil temperature (T) and unfrozen water content (M), to cover the frozen, partially frozen and unfrozen phases of successfully bioremediated, petroleum hydrocarbon-contaminated, sandy sub-Arctic soils. The Michaelis-Menten equation was modified to express the observable change in unfrozen water content near 0 °C, which is related to soil respiration activity during soil phase changes and at temperatures below the effective endpoint of detectable unfrozen water at -2 °C. The modified Michaelis-Menten equation was further combined with a Q10 temperature term, and was then incorporated into the GRESP equation to produce a new URESP model for the engineered soil bioremediation system at sub-zero temperatures. The URESP model was applied to published input data measured from the biostimulated site soils of a pilot-scale soil tank experiment conducted between -5 and 15 °C. The model fit well with the experimental data for CO2 production (R2 = 0.96) and O2 consumption (R2 = 0.92). A numerical soil thermal model (TEMP/W model) of the thawing biotreated soils in the tank was also used in this study to produce valid alternative (predictive) input T and M data for the URESP model. The URESP-derived respiration quotients (RQ; 0.695 to 0.698), or the ratios of CO2 production to O2 consumption, aligned with the experimental RQ values from the soil tank experiment (0.69) and fell within the theoretical RQ range for aerobic hydrocarbon degradation (0.63-0.80). The URESP model combined with the TEMP/W simulation approximated changes in soil respiration during thawing and characterized the computed soil respiration outputs as related to hydrocarbon utilization, based on their RQ values.

Decomposing P300 into correlates of genetic risk and current symptoms in schizophrenia: An inter-trial variability analysis.

BACKGROUND: The P300 event-related potential (ERP) component, which reflects cognitive processing, is a candidate biomarker for schizophrenia. However, the role of P300 in the pathophysiology of schizophrenia remains unclear because averaged P300 amplitudes reflect both genetic predisposition and current clinical status. Thus, we sought to identify which aspects of P300 are associated with genetic risk versus symptomatic status via an inter-trial variability analysis. METHODS: Auditory P300, clinical symptoms, and neurocognitive function assessments were obtained from forty-five patients with schizophrenia, thirty-two subjects at genetic high risk (GHR), thirty-two subjects at clinical high risk (CHR), and fifty-two healthy control (HC) participants. Both conventional averaging and inter-trial variability analyses were conducted for P300, and results were compared across groups using analysis of variance (ANOVA). Pearson's correlation was utilized to determine associations among inter-trial variability for P300, current symptoms and neurocognitive status. RESULTS: Average P300 amplitude was reduced in the GHR, CHR, and schizophrenia groups compared with that in the HC group. P300 inter-trial variability was elevated in the CHR and schizophrenia groups but relatively normal in the GHR and HC groups. Furthermore, P300 inter-trial variability was significantly related to negative symptom severity and neurocognitive performance results in schizophrenia patients. CONCLUSIONS: These results suggest that P300 amplitude is an endophenotype for schizophrenia and that greater inter-trial variability of P300 is associated with more severe negative and cognitive symptoms in schizophrenia patients.

Triptolide blocks the STAT3 signaling pathway through induction of protein tyrosine phosphatase SHP-1 in multiple myeloma cells.

Triptolide, an active component extracted from the medicinal plant Tripterygium wilfordii Hook F., has been used to treat various diseases, including lupus, cancer, rheumatoid arthritis and nephritic syndrome. The present study investigated the effects of triptolide on multiple myeloma using western blotting and an electrophoretic mobility shift assay. Triptolide was found to suppress the inducible and constitutive activation of signal transducer and activator of transcription 3 (STAT3), which is closely associated with inflammation and tumorigenesis. Triptolide also inhibited the DNA binding of STAT3. This correlated with the downregulation of Src kinase and Janus kinase 1 and 2, and with the upregulation of protein tyrosine phosphatase non­receptor type 6 (also known as SHP­1). In addition, triptolide downregulated the expression of the STAT3­regulated antiapoptotic (Bcl­xL and myeloid cell leukemia­1), proliferative (cyclin D1), and angiogenic (vascular endothelial growth factor) genes, suggesting that triptolide can induce apoptosis of tumor cells. These results suggest that triptolide may be a potential therapeutic anticancer agent for the prevention and treatment of multiple myeloma; thus further in­depth investigations into its efficacy and toxicity are warranted.

Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors.

The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent possessing the ability to induce apoptosis in various cancer cells but not in non­malignant cells. However, certain type of cancer cells are resistant to TRAIL­induced apoptosis and some acquire resistance after the first treatment. So development of an agent that can reduce or avoid resistance in TRAIL­induced apoptosis has garnered significant attention. The present study evaluated the anticancer potential of hispolon in TRAIL­induced apoptosis and indicated hispolon can sensitize cancer cells to TRAIL. As the mechanism of action was examined, hispolon was found to activate caspase­3, caspase­8 and caspase­9, while downregulating the expression of cell survival proteins such as cFLIP, Bcl­2 and Bcl­xL and upregulating the expression of Bax and truncated Bid. We also found hispolon induced death receptors in a non­cell type­specific manner. Upregulation of death receptors by hispolon was found to be p53-independent but linked to the induction of CAAT enhancer binding protein homologous protein (CHOP). Overall, hispolon was demonstrated to potentiate the apoptotic effects of TRAIL through downregulation of anti­apoptotic proteins and upregulation of death receptors linked with CHOP and pERK elevation.

Anticancer effect of fucoidan in combination with tyrosine kinase inhibitor lapatinib.

Background. Despite a number of in vitro and in vivo studies reporting the efficacy of fucoidan in treating various cancers, few studies have measured the efficacy of dietary fucoidan (DF) in combination with cancer drugs. Thus, we examined the sensitivity of DF in combination with the EGFR/ERBB2-targeting reagent lapatinib on cancer cells. Method. We selected six EGFR/ERBB2-amplified cancer cell lines (OE19, NCI-N87, OE33, ESO26, MKN7, and BT474) as an in vitro model and tested their sensitivity to DF alone and to DF in combination with the well-known EGFR/ERBB2-targeting reagent lapatinib. Result. Overall, in drug independent sensitivity test, DF alone did not significantly inhibit the growth of EGFR/ERBB2-amplified cancer cells in vitro. When DF was given in combination with lapatinib, however, it tended to synergistically inhibit cell growth in OE33 but antagonized the action of lapatinib in ESO26, NCI-N87, and OE19. Conclusion. This study suggests that DF has the potential to increase or decrease the effects of certain anticancer drugs on certain cancer cell types. Further study is needed to explore the mechanism of interaction and synergistic antitumor activity of DF in combination with chemotherapy and targeted therapy.

Flos Lonicera ameliorates obesity and associated endotoxemia in rats through modulation of gut permeability and intestinal microbiota.

BACKGROUND AND AIM: Increasing evidence has indicated a close association of host-gut flora metabolic interaction with obesity. Flos Lonicera, a traditional herbal medicine, is used widely in eastern Asia for the treatment of various disorders. The aim of this study was to evaluate whether unfermented or fermented formulations of Flos Lonicera could exert a beneficial impact to combat obesity and related metabolic endotoxemia. METHODS: Obesity and metabolic endotoxemia were induced separately or together in rats through feeding a eight-week high fat diet either alone (HFD control group) or in combination with a single LPS stimulation (intraperitoneal injection, 0.75 mg/kg) (LPS control group). While, the mechanism of action of the Lonicera formulations was explored in vitro using RAW 264.7 and HCT 116 cell lines as models. RESULTS: In cell-based studies, treatment with both unfermented Flos Lonicera (UFL) and fermented Flos Lonicera (FFL) formulations resulted in suppression of LPS-induced NO production and gene expression of vital proinflammatory cytokines (TNF-α, COX-2, and IL-6) in RAW 264.7 cells, reduced the gene expression of zonula occludens (ZO)-1 and claudin-1, and normalized trans epithelial electric resistance (TEER) and horseradish peroxidase (HRP) flux in LPS-treated HCT-116 cells. In an animal study, treatment of HFD as well as HFD+LPS groups with UFL or FFL resulted in a notable decrease in body and adipose tissue weights, ameliorated total cholesterol, HDL, triglyceride, aspartate transaminase and endotoxin levels in serum, reduced the urinary lactulose/mannitol ratio, and markedly alleviated lipid accumulation in liver. In addition, exposure of HFD as well as HFD+LPS groups with UFL or FFL resulted in significant alteration of the distribution of intestinal flora, especially affecting the population of Akkermansia spp. and ratio of Bacteroidetes and Firmicutes. CONCLUSION: This evidence collectively demonstrates that Flos Lonicera ameliorates obesity and related metabolic endotoxemia via regulating distribution of gut flora and gut permeability.

Glucose oxidase nanotube-based enzymatic biofuel cells with improved laccase biocathodes.

Glucose/O(2) biofuel cells (BFCs) with an improved power density and stability were developed, using glucose oxidase (GOD) nanotubes with polypyrrole (PPy)-carbon nanotubes (CNTs)-GOD layers deposited on their surface as an anode and a PPy-laccase-2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) diammonium salt (ABTS) film type cathode. The GOD nanotubes were fabricated within the nanopores of an anodized aluminum oxide membrane using a template-assisted layer-by-layer deposition method. These BFCs exhibited a higher volumetric power than the best performance reported previously; this was likely due to an increase in enzyme loading of GOD nanotubes and improved electrochemical properties of the PPy-CNTs-GOD layers. The stability of BFCs was closely related to the leakage of ABTS from the cathode. When the leakage of ABTS was suppressed, the power density of BFCs was nearly unchanged for at least 8 days under physiological conditions.