Effects of joint mobilization combined with acupuncture on pain, physical function, and depression in stroke patients with chronic neuropathic pain: A randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of joint mobilization (JM) combined with acupuncture (AC) for the treatment of pain, physical function and depression in poststroke patients. METHODS: A total of 69 poststroke patients were randomly assigned to the JM+AC group (n = 23), the JM group (n = 23), and the control group (n = 23). Patients in the JM+AC group and the JM group received JM for 30 minutes, twice a week for 12 weeks, and the JM+AC group received AC for 30 minutes separately once a week. The control group did not receive JM or AC. Pain (visual analog scale, shoulder pain and disability index, Western Ontario and McMaster universities osteoarthritis index), physical function (range of motion, 10-m walking speed test, functional gait assessment, manual function test, activities of daily living scale, instrumental activities of daily living scale), and depression (center for epidemiologic studies depression scale, Beck depression inventory) were assessed for each patient before and after the 12 weeks of intervention. RESULTS: Pain and physical function were improved significantly in the JM+AC group compared with the JM and control groups. Physical function and depression were improved significantly in the JM+AC and JM groups compared with the control group. CONCLUSION: The treatment of JM combined with AC improved pain, depression, and physical function of poststroke patients with chronic neuropathic pain in this study. This valuable finding provides empirical evidence for the designing therapeutic interventions and identifying potential therapeutic targets.

Weissella koreensis and Pediococcus pentosaceus bacterial ghosts induce inflammatory responses as immunostimulants.

In this study, bacterial ghosts (BGs) were generated from Weissella koreensis LKS42 (WKorGs) and Pediococcus pentosacues KA94 (PPGs) by chemically inducing lysis using substances such as hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), acetic acid (CH3COOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), sodium carbonate (Na2CO3), n-butanol, and C6H8O7. HCl-induced WKorGs and PPGs exhibited complete removal of DNA and displayed transverse membrane dissolution tunnel structures under scanning electron microscopy (SEM). Cell viability assays showed high viability of RAW 264.7 cells exposed to HCl-induced WKorGs and PPGs. Additionally, treatment with HCl-induced WKorGs and PPGs elevated mRNA levels of pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α, iNOS) and the anti-inflammatory cytokine IL-10 in RAW 264.7 cells. These findings suggest that HCl-induced WKorGs and PPGs have the potential to be used as inactivated bacterial immunostimulants, highlighting their promising applications in immunization and immunotherapy.

Anti-Leukemic Effects of Idesia polycarpa Maxim Branch on Human B-Cell Acute Lymphoblastic Leukemia Cells.

Patients with pediatric B-cell acute lymphoblastic leukemia (B-ALL) have a high survival rate, yet the prognosis of adults and patients with relapsed/refractory disease is relatively poor. Therefore, it is imperative to develop new therapeutic strategies. Here, we screened 100 plant extracts from South Korean Flora and investigated their anti-leukemic effect using CCRF-SB cells as a B-ALL model. The top cytotoxic extract identified in this screening was the Idesia polycarpa Maxim. branch (IMB), which efficiently inhibited the survival and proliferation of CCRF-SB cells, while having minimal to no impact on normal murine bone marrow cells. Mechanistically, the IMB-induced proapoptotic effect involves the increase of caspase 3/7 activity, which was shown to be associated with the disruption of the mitochondrial membrane potential (MMP) through the reduction in antiapoptotic Bcl-2 family expression. IMB also promoted the differentiation of CCRF-SB cells via the upregulation of the expression of differentiation-related genes, PAX5 and IKZF1. Given that resistance to glucocorticoid (GC) is often found in patients with relapsed/refractory ALL, we investigated whether IMB could restore GC sensitivity. IMB synergized GC to enhance apoptotic rate by increasing GC receptor expression and downmodulating mTOR and MAPK signals in CCRF-SB B-ALL cells. These results suggest that IMB has the potential to be a novel candidate for the treatment of B-ALL.

The effects of herbal medicine (Jujadokseo-hwan) on quality of life in patients with mild cognitive impairment: Cost-effectiveness analysis alongside randomized controlled trial.

Background: Mild cognitive impairment (MCI), the early stage of dementia, requires effective intervention for symptom management and improving patients' quality of life (QoL). Jujadokseo-hwan (JDH) is a Korean herbal medicine prescription used to improve MCI symptoms, such as memory deficit. This study evaluates the improvement in QoL through JDH. Alongside a clinical trial, it estimates the cost-effectiveness of JDH, compared to placebo, for MCI over 24 weeks. Methods: Changes in QoL were measured using the EuroQol-5 Dimensions (EQ-5D) and Korean version QoL-Alzheimer's Disease (KQOL-AD). Direct medical and non-medical costs were surveyed and incremental cost-effectiveness ratios (ICER) per QALY for JDH were produced. Results: In total, 64 patients were included in the economic evaluation (n = 35 in JDH, n = 29 in placebo). In the JDH group, EQ-5D and KQOL-AD improved by 0.020 (p = .318) and 3.40 (p = .011) over 24 weeks, respectively. In the placebo group, they increased by 0.001 (p=.920) and 1.07 (p=.130), respectively. The ICER was KRW 76,400,000 per QALY and KRW 108,000 per KQOL-AD for JDH, compared to the placebo group. Conclusion: JDH is not considered a cost-effective treatment option compared with placebo; however, it positively affects QoL improvement in patients with MCI.

Design and Optimization of Rivaroxaban-Cyclodextrin-Polymer Triple Complex Formulation with Improved Solubility.

Purpose: This study aimed to ensure the convenience of administration and reproducibility of efficacy, regardless of the meal, by improving the solubility of rivaroxaban (RIV). Methods: RIV is a non-vitamin K antagonist oral anticoagulants that exhibits a coagulation effect by directly inhibiting coagulation factor Xa. However, RIV has a very low solubility; therefore, it must be administered with a meal at high doses. We used a drug- hydroxypropyl-beta-cyclodextrin (CD)-water-soluble polymer triple complex (R-C-P complex) to solubilize RIV. Using Minitab, we evaluated the effect of each factor on RIV solubility and developed an optimal R-C-P complex formulation. The amount of CD, amount of polymer, and polymer type were set as the independent variables X1, X2, and X3, respectively. RIV solubility (Y1) and dissolution rate for 45 min in pH 4.5 medium (Y2) and pH 1.2 medium (Y3) were set as response variables. Results: The most efficient RIV solubilization effect was obtained from the composition using CD and HPMC 2208, and physicochemical properties and dissolution parameters were analyzed. RIV in the R-C-P complex was present in an amorphous form and showed high solubility. Unlike commercial products, it showed a 100% dissolution rate. The R-C-P complex formulation secured high RIV solubility and 100% release regardless of pH. Conclusion: The results imply that high-dose RIV can be administered regardless of the meal, reducing the risk of changing the drug effect due to the patient's administration mistake.

The Cost-Effectiveness Analysis of Gamiguibi-Tang versus Hwangryunhaedok-Tang for Patients with Insomnia Disorder Based on a Randomized Controlled Trial.

(1) Insomnia is associated with poor quality of life and loss of productivity, and is a significant economic burden on society. Gamiguibi-tang (GGBT) is the most frequently prescribed herbal medicine for insomnia treatment. Hwangryunhaedok-tang (HHT) is used as an insured herbal medicine for insomnia in the Korean National Health Insurance (NHI) system. This study aims to evaluate the cost-effectiveness of GGBT versus HHT in patients with insomnia disorders based on clinical trial data; (2) Methods: The EuroQol five-dimension scale (EQ-5D) was used to estimate quality-adjusted life-years (QALY). Direct and non-direct medical costs and lost productivity costs were estimated. The cost-effectiveness of GGBT was compared with HHT treatments over six weeks from a societal perspective; (3) Results: A total of 81 patients who underwent GGBT (n = 56) and HHT (n = 25) treatment completed the clinical trial. The EQ-5D score improved significantly more in the GGBT than in the HHT group (0.02 vs. −0.03, p < 0.05). The QALYs for six weeks were slightly greater in GGBT (0.0997) than in the HHT group (0.0987); however, the total costs incurred were approximately 9% less in GGBT ($934) than in the HHT group ($1029). GGBT was found to be a more economically dominant treatment option compared to HHT for treating insomnia; (4) Conclusions: Among herbal medicines, GGBT may be a cost-effective option for treating insomnia from a societal perspective in Korea.

Cancer therapeutics based on diverse energy sources.

Light-based phototherapy has been developed for cancer treatment owing to its non-invasiveness and spatiotemporal control. Despite the unique merits of phototherapy, one critical disadvantage of light is its limited penetration depth, which restricts its application in cancer treatment. Although many researchers have developed various strategies to deliver light into deep-seated tumors with two-photon and near-infrared light irradiation, phototherapy encounters the peculiar limitations of light. In addition, high oxygen dependency is another limitation of photodynamic therapy to treat hypoxic tumors. To overcome the drawbacks of conventional treatments, various energy sources have been developed for cancer treatment. Generally, most energy sources, such as ultrasound, chemiluminescence, radiation, microwave, electricity, and magnetic field, are relatively free from the restraint of penetration depth. Combining other strategies or therapies with other energy-source-based therapies improves the strength and compensates for the weakness. This tutorial review focuses on recent advances in the diverse energy sources utilized in cancer treatment and their future perspectives.

Analysis of the cause and management of persistent laboratory abnormalities occurring after the surgical treatment of primary hyperparathyroidism.

Purpose: The surgical success rate for primary hyperparathyroidism (PHPT) is currently 95%-98%. However, 3%-24% of patients show persistently elevated (Pe) parathyroid hormone (PTH) levels after parathyroidectomy (PTX). This single-center retrospective study aimed to compare the outcomes of patients with normal PTH and PePTH levels after successful PTX and to identify the factors associated with PePTH. Methods: The normal group, defined as patients with normal serum calcium and PTH levels immediately after PTX, was compared with the PePTH group (patients with normal or low serum calcium and increased serum PTH levels up to 6 months postoperatively) to determine the causes of disease in the PePTH group. Results: There were no significant differences in age, sex, or preoperative estimated glomerular filtration rate between the normal PTH group (333 of 364, 91.5%) and the PePTH group (31 of 364, 8.5%). However, there were significant differences in preoperative 25-hydroxyvitamin D (17.9 and 11.8 ng/mL, respectively; P = 0.003) and PTH levels (125.5 and 212.4 pg/mL, respectively; P < 0.001) between the 2 groups. Among the 31 cases of the PePTH group, 18 were attributed to vitamin D deficiency. Conclusion: Preoperative vitamin D deficiency is a predictive factor for PePTH. Therefore, preoperative administration of vitamin D supplements may reduce the probability of postoperative disease persistence. Patients with temporary laboratory abnormalities within 6 months after successful PTX should be monitored, and appropriate vitamin D and calcium supplementation may reduce the effort and cost of various examinations or reoperations.

Traditional East Asian Herbal Medicine Treatment for Alzheimer's Disease: A Systematic Review and Meta-Analysis.

Alzheimer's disease (AD) is a leading progressive neurodegenerative disease worldwide, and its treatment is a challenging clinical problem. This review was conducted to evaluate the efficacy and safety of herbal medicine for AD treatment. The PubMed, CENTRAL, EMBASE, CNKI, OASIS, KTKP, and CiNii databases were searched until June 2020 for randomized controlled trials (RCTs) on herbal medicine for AD, and a meta-analysis of 57 RCTs was conducted. For cognitive function, herbal medicine significantly improved the Mini-Mental State Examination (MMSE) and AD Assessment Scale-Cognitive Subscale (ADAS-cog) scores compared with conventional medicine. The MMSE scores showed no significant difference between the groups treated with herbal medicine and donepezil; however, herbal medicine significantly lowered the ADAS-cog score. Acori Graminei Rhizoma-containing and Cnidii Rhizoma-containing herbal medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine showed a positive, but not statistically significant, tendency toward improving the MMSE score compared with conventional medicine. Herbal medicine with conventional medicine significantly improved the MMSE, ADAS-cog, and Montreal Cognitive Assessment (MoCA) scores compared with conventional medicine, and herbal medicine with donepezil also significantly improved these scores compared with donepezil. Acori Graminei Rhizoma or Cnidii Rhizoma-containing herbal medicine with conventional medicine significantly improved the MMSE and ADAS-cog scores compared with conventional medicine. Ginseng Radix-containing herbal medicine + conventional medicine significantly improved the MMSE score, but not the ADAS-cog score, compared with conventional medicine. For behavioral and psychological symptoms of dementia, the Neuropsychiatry Inventory (NPI) score was not significantly different between herbal and conventional medicines. Herbal medicine with conventional medicine significantly improved the NPI and Behavioral Pathology in Alzheimer's Disease Rating Scale scores compared with conventional medicine. The NPI score showed no significant difference between the groups treated with herbal medicine and placebo. Furthermore, herbal medicine with conventional medicine significantly lowered plasma amyloid beta levels compared with conventional medicine alone. Herbal medicine, whether used alone or as an adjuvant, may have beneficial effects on AD treatment. However, owing to the methodological limitations and high heterogeneity of the included studies, concrete conclusions cannot be made.

Effect of High Hydrostatic Pressure Treatment on Urease Activity and Inhibition of Fishy Smell in Mackerel (Scomber japonicus) during Storage.

In this study, the physicochemical changes related to fishy smell were determined by storing high hydrostatic pressure (HHP)-treated mackerel (Scomber japonicus) meat in a refrigerator for 20 days. The inhibition of crude urease activity from Vibrio parahaemolyticus using HHP treatment was also investigated. The mackerel meat storage experiment demonstrated that production of trimethylamine (TMA) and volatile basic nitrogen (VBN), the main components of fishy smell, was significantly reduced on the 20th day of storage after the HHP treatment compared to the untreated mackerels. The results demonstrated that the increased ammonia nitrogen rates in the 2000, 3000, and 4000 bar, HHP-treated groups decreased by 23.8%, 23.8%, and 31.0%, respectively, compared to the untreated groups. The enzyme activity of crude urease was significantly reduced in the HHP-treated group compared to that in the untreated group. Measurement of the volatile organic compounds (VOCs) in mackerel meat during storage indicated that the content of ethanol, 2-butanone, 3-methylbutanal, and trans-2-pentenal, which are known to cause off-flavor due to spoilage, were significantly reduced by HHP treatment. Collectively, our results suggested that HHP treatment would be useful for inhibiting the activity of urease, thereby reducing the fishy smells from fish and shellfish.

Anticancer Activity of Continentalic Acid in B-Cell Lymphoma.

Aralia continentalis has been used in Korea as a folk remedy for arthralgia, rheumatism, and inflammation. However, its anti-lymphoma effect remains uncharacterized. Here, we demonstrate that A. continentalis extract and its three diterpenes efficiently kill B-lymphoma cells. Our in vitro and in vivo results suggest that the cytotoxic activities of continentalic acid, a major diterpene from A. continentalis extract, are specific towards cancer cells while leaving normal murine cells and tissues unharmed. Mechanistically, continentalic acid represses the expression of pro-survival Bcl-2 family members, such as Mcl-1 and Bcl-xL. It dissociates the mitochondrial membrane potential, leading to the stimulation of effector caspase 3/7 activities and, ultimately, cell death. Intriguingly, this agent therapeutically synergizes with roflumilast, a pan-PDE4 inhibitor that has been successfully repurposed for the treatment of aggressive B-cell malignancies in recent clinical tests. Our findings unveiled that A. continentalis extract and three of the plant's diterpenes exhibit anti-cancer activities. We also demonstrate the synergistic inhibitory effect of continentalic acid on the survival of B-lymphoma cells when combined with roflumilast. Taken in conjunction, continentalic acid may hold significant potential for the treatment of B-cell lymphoma.

Antioxidant Activity and Inhibitory Effect on Nitric Oxide Production of Hydroponic Ginseng Fermented with Lactococcus lactis KC24.

Panax ginseng Meyer is used as a medicinal plant. The aim of this study was to ferment hydroponic ginseng with Lactococcus lactis KC24 and confirm its antioxidant activity and inhibitory effect on nitric oxide (NO) production. Flavonoid and phenol contents in fermented ginseng extracts were measured. Antioxidant activity was measured by DPPH, ABTS, reducing power, FRAP and ß-carotene assays. Additionally, inhibitory effects on NO production and toxicity of the fermented extract were determined using RAW 264.7 cells. Phenol and flavonoid contents increased as the fermentation time increased, and the contents were higher in hydroponic ginseng than in soil-cultivated ginseng. The DPPH assay revealed that the antioxidant activity of the 24 h fermented extract significantly increased from 32.57% to 41% (p < 0.05). The increase in antioxidant activity may be affected by an increase in phenol and flavonoid contents. At 1 mg/mL solid content, the 24 h fermented hydroponic ginseng extract inhibited NO production from 9.87 ± 0.06 µM to 1.62 ± 0.26 µM. In conclusion, the increase in antioxidant activity affects the inhibition of NO production, suggesting that fermented hydroponic ginseng may be used in the industries of functional food and pharmaceutical industry as a functional material with anti-inflammatory effects.

Antimicrobial Activity and Action Mechanisms of Arg-Rich Short Analog Peptides Designed from the C-Terminal Loop Region of American Oyster Defensin (AOD).

American oyster defensin (AOD) was previously purified from acidified gill extract of the American oyster, Crassostrea virginica. AOD is composed of 38 amino acids with three disulfide bonds and exhibits strong antimicrobial activity against Gram-positive bacteria as well as significant activity against Gram-negative bacteria. Here, to develop promising peptides into antibiotic candidates, we designed five arginine-rich analogs (A0, A1, A2, A3, and A4), predicted their loop and extended strand/random structures-including nine amino acids and a disulfide bond derived from the C-terminus of AOD-and described their antimicrobial and cytotoxic effects, as well as their modes of action. In our experimental results, the A3 and A4 analogs exhibited potent antimicrobial activity against all test organisms-including four Gram-positive bacteria, six Gram-negative bacteria, and Candida albicans-without cell toxicity. A sequence of experiments, including a membrane permeabilization assay, DNA binding study, and DNA polymerization inhibition test, indicated that the two analogs (A3 and A4) possibly did not act directly on the bacterial membrane but instead interacted with intracellular components such as DNA or DNA amplification reactions. AOD analogs also showed strong bacterial inhibition activity in the plasma environment. In addition, analog-treated microbial cells clearly exhibited membrane disruption, damage, and leakage of cytoplasmic contents. Collectively, our results suggest that two analogs, A3 and A4, have potent antimicrobial activity via DNA interaction and have the potential for development into novel antimicrobial agents.

Interventions to improve district-level routine health data in low-income and middle-income countries: a systematic review.

BACKGROUND: Routine health information system(s) (RHIS) facilitate the collection of health data at all levels of the health system allowing estimates of disease prevalence, treatment and preventive intervention coverage, and risk factors to guide disease control strategies. This core health system pillar remains underdeveloped in many low-income and middle-income countries. Efforts to improve RHIS data coverage, quality and timeliness were launched over 10 years ago. METHODS: A systematic review was performed across 12 databases and literature search engines for both peer-reviewed articles and grey literature reports on RHIS interventions. Studies were analysed in three stages: (1) categorisation of RHIS intervention components and processes; (2) comparison of intervention component effectiveness and (3) whether the post-intervention outcome improved above the WHO integrated disease surveillance response framework data quality standard of 80% or above. RESULTS: 5294 references were screened, resulting in 56 studies. Three key performance determinants-technical, organisational and behavioural-were proposed as critical to RHIS strengthening. Seventy-seven per cent [77%] of studies identified addressed all three determinants. The most frequently implemented intervention components were 'providing training' and 'using an electronic health management information systems'. Ninety-three per cent [93%] of pre-post or controlled trial studies showed improvements in one or more data quality outputs, but after applying a standard threshold of >80% post-intervention, this number reduced to 68%. There was an observed benefit of multi-component interventions that either conducted data quality training or that addressed improvement across multiple processes and determinants of RHIS. CONCLUSION: Holistic data quality interventions that address multiple determinants should be continuously practised for strengthening RHIS. Studies with clearly defined and pragmatic outcomes are required for future RHIS improvement interventions. These should be accompanied by qualitative studies and cost analyses to understand which investments are needed to sustain high-quality RHIS in low-income and middle-income countries.

Tailoring photosensitive ROS for advanced photodynamic therapy.

Photodynamic therapy (PDT) has been considered a noninvasive and cost-effective modality for tumor treatment. However, the complexity of tumor microenvironments poses challenges to the implementation of traditional PDT. Here, we review recent advances in PDT to resolve the current problems. Major breakthroughs in PDTs are enabling significant progress in molecular medicine and are interconnected with innovative strategies based on smart bio/nanomaterials or therapeutic insights. We focus on newly developed PDT strategies designed by tailoring photosensitive reactive oxygen species generation, which include the use of proteinaceous photosensitizers, self-illumination, or oxygen-independent approaches. While these updated PDT platforms are expected to enable major advances in cancer treatment, addressing future challenges related to biosafety and target specificity is discussed throughout as a necessary goal to expand the usefulness of PDT.

Patients with Parkinson Disease in a Traditional Korean Medicine Hospital: A Five-Year Audit.

Parkinson disease (PD) patients' demand for complementary and alternative medicine (CAM) has thus been increasing. We investigated the characteristics of PD patients who visited the Korean Medicine Hospital, the official CAM clinic in Korea. The medical records of PD patients were reviewed retrospectively. The demographic and disease-related characteristics, motivation for visiting, and treatment modalities were collected and analyzed. Medical records from 618 patients were reviewed. Most patients (67.6%) had been already diagnosed with PD at the initial visit. The most frequent complaint was gait disturbance. Previously diagnosed patients visited most frequently for add-on CAM therapies. The most frequently used CAM therapy was acupuncture. The most frequently prescribed herbal medicine was modified Ukgansan. We found the main reason for seeking out CAM was to compensate for the effects of conventional therapies. Further prospective studies will be necessary to collect enough data and evaluate the effectiveness of CAM therapies.

Herbal medicine treatment for patients with chronic subdural hematoma: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: In Asian countries, herbal medicines have been used to treat Chronic subdural hematoma (CSDH) as an adjunctive therapy. This review aims to evaluate the efficacy and safety of herbal medicine on treating CSDH and preventing recurrent CSDH. METHODS: A literature search was conducted on PubMed, CENTRAL, Scopus, CiNii, KTKP, NDSL, OASIS, and CNKI for randomized controlled trials that evaluated the effects of herbal medicines on CSDH. RESULTS: Seven studies (n = 646) were included. The overall methodological quality of these studies was low. In the herbal group, the meta-analysis indicated statistically significant improvements in the total effective rate and recurrence rate as compared with those in the non-herbal group. Herbal treatments were found to be relatively safe. CONCLUSION: Herbal medicines might be efficacious in the management of CSDH and prevent its recurrence. Further rigorous studies will have to be conducted in order to make more definite conclusions.

Herbal medicine treatment for Alzheimer disease: A protocol for a systematic review and meta-analysis.

BACKGROUND: Alzheimer disease (AD) is a leading progressive neurodegenerative disease worldwide, but treating it is challenging in clinical practice. This review is aimed at evaluating the efficacy and safety of herbal medicine for treating AD. METHODS AND ANALYSIS: We will search for randomized controlled trials related to the effect and safety of herbal medicine for AD in the following databases: PubMed, Cochrane Central Register of Controlled Trials, Excerpta Medica Database, China National Knowledge Infrastructure database, Oriental Medicine Advanced Searching Integrated system, Korean Traditional Knowledge Portal, and Citation Information by National Institute for Informatics. The risk of bias will be evaluated using the Cochrane risk-of-bias assessment tool. After screening the studies, a meta-analysis will be performed. The primary outcome will be the Mini-Mental State Examination score. Secondary outcomes will consist of other scales for cognitive function and other aspects, such as behavioral and psychological symptoms and plasma levels of amyloid-ß. RESULTS: This study will provide the current status of evidence for herbal medicine to treat AD. CONCLUSION: The results of this review will determine the efficacy and safety of herbal medicine for AD. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on a review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. TRIAL REGISTRATION NUMBER: Research Registry reviewregistry933.

Reactive oxygen species mediated-antifungal activity of cinnamon bark (Cinnamomum verum) and lemongrass (Cymbopogon citratus) essential oils and their constituents against two phytopathogenic fungi.

To find new and safe type of control agents against phytopathogenic fungi, the fumigant antifungal activity of 10 plant essential oils and constituents identified in cinnamon bark (Cinnamomum verum) and lemongrass (Cymbopogon citratus) essential oils was investigated against two phytopathogenic fungi, Raffaelea quercus-mongolicae and Rhizoctonia solani. Among plant essential oils, cinnamon bark and lemongrass essential oils showed 100% inhibition of R. quercus-mongolicae and R. solani at 5 mg/paper disc, respectively. Among test constituents, salicylaldehyde, eugenol, and hydrocinnamaldehyde showed 100% inhibition of growth of R. quercus-mongolicae at 2.5 mg/paper disc. Neral, geraniol, geranial, trans-cinnamaldehyde, methyl cinnamate, isoeugenol, and methyl eugenol exhibited >80% inhibition of growth of R. quercus-mongolicae at 2.5 mg/paper disc. Neral, geranial, trans-cinnamaldehyde, hydrocinnamaldehyde, and salicylaldehyde showed 100% inhibition of growth of R. solani at 2.5 mg/paper disc. A fumigant antifungal bioassay of artificial blends of the constituents identified in cinnamon bark and lemongrass essential oils indicated that trans-cinnamaldehyde and geranial were major contributors to the fumigant antifungal activity of the artificial blend. Confocal laser scanning microscopy images of fungi treated with cinnamon bark and lemongrass essential oils, trans-cinnamaldehyde, neral, and geranial revealed the reactive oxygen species (ROS) generation and cell membrane disruption.

Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System.

The metabolic state of the brain can greatly impact neurologic function. Evidence of this includes the therapeutic benefit of a ketogenic diet in neurologic diseases, including epilepsy. However, brain lipid bioenergetics remain largely uncharacterized. The existence, capacity, and relevance of mitochondrial fatty acid ß-oxidation (FAO) in the brain are highly controversial, with few genetic tools available to evaluate the question. We have provided evidence for the capacity of brain FAO using a pan-brain-specific conditional knockout (KO) mouse incapable of FAO due to the loss of carnitine palmitoyltransferase 2, the product of an obligate gene for FAO (CPT2B-/-). Loss of central nervous system (CNS) FAO did not result in gross neuroanatomical changes or systemic differences in metabolism. Loss of CPT2 in the brain did not result in robustly impaired behavior. We demonstrate by unbiased and targeted metabolomics that the mammalian brain oxidizes a substantial quantity of long-chain fatty acids in vitro and in vivo Loss of CNS FAO results in robust accumulation of long-chain acylcarnitines in the brain, suggesting that the mammalian brain mobilizes fatty acids for their oxidation, irrespective of diet or metabolic state. Together, these data demonstrate that the mammalian brain oxidizes fatty acids under normal circumstances with little influence from or on peripheral tissues.