Safety and Efficacy of HL301 In Radiation Pneumonitis in Patients With Unresectable Non-Small Cell Lung Cancer Receiving Curative Concurrent Chemoradiotherapy: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled, Phase 2a Clinical Trial.

PURPOSE: We aimed to investigate the safety and efficacy of HL301, a standardized combination product of 7 medicinal plants, in radiation pneumonitis in patients with unresectable non-small cell lung cancer undergoing curative concurrent chemoradiotherapy. METHODS AND MATERIALS: The target accrual was 87 and a total of 63 patients were enrolled due to poor accrual rate. We randomly assigned the 63 patients to receive a placebo (arm A), or 1200 mg HL301 (arm B), or 1800 mg HL301 (arm C). Patients received weekly paclitaxel and carboplatin concurrently with intensity-modulated radiation therapy at 60 to 66 Gy in conventional fractionation. Durvalumab was administered as a maintenance treatment according to standard clinical practice. HL301 was administered orally, daily for 12 weeks. The primary endpoint was incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy. RESULTS: The baseline characteristics of the patients were well balanced. The drug was tolerable with a compliance rate of 86.6%, 86.2%, and 88.8% in arms A, B, and C, respectively (P = .874). None of the patients experienced severe drug-related adverse events. No significant difference in the rate of adverse events were observed between the treatment arms. The incidence of grade ≥2 radiation pneumonitis at 24 weeks postchemoradiotherapy was 37.5% (95% CI, 18.5%-61.4%), 55.6% (95% CI, 33.7%-75.4%), and 52.4% (95% CI, 32.4%-71.7%) in arms A, B, and C, respectively (P = .535). CONCLUSIONS: This is the first exploratory clinical trial to test the safety and efficacy of HL301 in patients with non-small cell lung cancer. Safety and feasibility of HL301 were established but no signals of efficacy in reducing radiation pneumonitis was observed in this dose level.

Protective Effect of Borassus flabellifer Haustorium Extract against Alkoxyl Radical-Induced Cytotoxicity by Improving Glutathione Metabolism by Modulating Nrf2/Haeme Oxygenase-1 Expression.

AIM: The study was aimed to assess the ability of Borassus flabellifer haustorium methanolic extract (BHE) on de novo glutathione biosynthesis in normal and pro-oxidant exposed cells via Nuclear factor erythroid 2-related factor 2 (Nrf2) and haeme oxygenase-1 (HO1) signaling in 2,2'-Azobis(2-methylpropionamidine) di-hydrochloride (AAPH) induced cytotoxicity in normal intestinal epithelial cells (IEC-6 cells). METHODS: The in vitro antioxidant activity was determined in terms of radical scavenging and ex vivo hemolysis. The cytoprotective effect was studied using AAP H as the alkoxyl radical inducer in IEC-6 cell model. The mechanistic basis of protection is determined by Nrf2/HO1 expression using qPCR. RESULTS: In vitro screening observed DPPH, hydrogen peroxide and ABTS radical scavenging activity for the BHE; further, BHE also protected the oxidative hemolysis in the erythrocytes induced by AAPH. In IEC-6 cells, AAPH treatment significantly reduced the cell viability (p < 0.001) by inducing lipid peroxidation. Further, there observed a significant reduction in the activities of enzymes involved in the de novo glutathione biosynthesis (p < 0.01) and glutathione reductase in these cells. However, pretreatment with BHE (10, 25 and 50 µg/mL) dose-dependently protected from the cytotoxicity of AAPH-derived alkoxyl radicals (p < 0.05); besides, the de novo glutathione biosynthesis and regeneration of GSH from oxidized form was also increased in these cells. In corroboration with the biochemical parameters, the Nrf2/HO1 expression was upregulated by the BHE pretreatment concomitantly reducing the cellular lipid peroxidation products. The improvement glutathione biosynthesis was also observed in BHE alone treated cells. CONCLUSION: The study indicated the potential of methanolic extract of Borassus flabellifer haustorium in enhancing the de novo glutathione biosynthesis in normal and pro-oxidant exposed cells by Nrf2/HO1 dependent manner, concomitantly mitigating the toxicity of AAPH-derived alkoxyl radicals in intestinal epithelial cells.

Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (Mpro) with pharmacokinetics and toxicological properties.

BACKGROUND: The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (Mpro). Therefore, identification of natural and effective Mpro inhibitors could be a safe and promising approach for COVID-19 control. METHODS: The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on Mpro by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with Mpro was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer. RESULTS: The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (Mpro) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity. CONCLUSIONS: The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.

Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs.

Garlic (Allium sativum L.), is a predominant spice, which is used as an herbal medicine and flavoring agent, since ancient times. It has a rich source of various secondary metabolites such as flavonoids, terpenoids and alkaloids, which have various pharmacological properties. Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC). The phytocompounds of garlic were identified by gas chromatography-mass spectrometry (GC-MS) technique. Subsequently, the identified phytocompounds were subjected to molecular docking to predict the binding with the drug targets, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) and group IIa secretory phospholipase A2 (sPLA2-IIA). Molecular dynamics is used to predict the stability of the identified phytocompounds against NSCLC drug targets by refining the intermolecular interactions formed between them. Among the 12 phytocompounds of garlic, three compounds[1,4-dimethyl-7-(1-methylethyl)-2-azulenyl]phenylmethanone, 2,4-bis(1-phenylethyl)-phenol and 4,5-2 h-oxazole-5-one,4-[3,5-di-t-butyl-4-methoxyphenyl] methylene-2-phenyl were identified as potential inhibitors, which might be suitable for targeting the different clinical forms of EGFR and dual inhibition of the studied drug targets to combat NSCLC. The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC.

In-vitro phytochemical and pharmacological bio-efficacy studies on Azadirachta indica A. Juss and Melia azedarach Linn for anticancer activity.

In this study, phyto-constituents, anti-bacterial and anticancer activity of Azadirachta indica A. Juss and Melia azedarach Linn was analyzed. High Performance Liquid Chromatography (HPLC) and Thin Layer Chromatography (TLC) fingerprint profile of methanol extract of A. indica and M. azedarach was carried out. The present findings showed the presence of phytochemicals such as, steroids, alkaloids, phenols, flavonoids, saponins, tannins, anthraquinone and aminoacids in A. indica and M. azedarach extracts. HPLC profiling of methanolic extract of A. indica and M. azaderach revealed eleven and ten fractions of compounds were visualized in the form of peak. In TLC methanolic extract of A. indica was separated by eight distinct phenolic and three steroidal bands and M. azaderach showed sixteen distinct phenolic and three different steroidal bands. In antibacterial activity, Among the various extracts 50 µg/ml methanolic extracts of A. indica showed high activity against K. pneumoniae (14 mm) and M. azedarach showed high activity against S. aureus (15 mm). The results suggest that the crude methanolic extracts of A. indica and M. azedarach possess significant phytochemical properties compared to other extracts and hence the phytochemicals of M. azedarach and A. indica can be exploited for plant based anticancer and antimicrobial agents in the near future.

Valeriana fauriei Exerts Antidepressant-Like Effects Through Anti-inflammatory and Antioxidant Activities by Inhibiting Brain-Derived Neurotrophic Factor Associated with Chronic Restraint Stress.

Although depression is the most common psychiatric disorder, its pharmacological properties are not well known yet. It has been reported that Valeriana fauriei (VF) extract is beneficial for several neurological diseases. However, little information is available regarding its antidepressant activity. Therefore, the objective of this study was to determine antidepressant activity of VF and the underlying mechanism involved in its effect on chronic restraint stress (CRS)-induced depression using a mouse model. Oral treatment of VF extract for 14 days significantly ameliorated depression-like behavior (immobility time) in forced swimming and tail suspension tests following CRS induction, in accordance with decreased levels of serum corticosterone. VF extract ameliorated c-Fos expression, microglial activation, phosphorylated p38 expression, and inflammatory response (protein expression levels of cyclooxygenase-2 and inducible nitric oxide) in the prefrontal cortex, hippocampus, and amygdala of mice after CRS induction. However, VF extract enhanced the stimulation of nuclear factor erythroid 2-related factor 2 pathways, in accordance with upregulation in protein expression of brain-derived neurotrophic factor (BDNF). Collectively, our findings demonstrate that VF extract has antidepressant-like activity against CRS-induced depression through its anti-inflammatory and antioxidant effects by inhibiting BDNF expression. Further studies are warranted to investigate VF extract's fraction and components to develop possible antidepressants.

Prophylactic efficacy of Boerhavia diffusa L. aqueous extract in toluene induced reproductive and developmental toxicity in Drosophila melanogaster.

BACKGROUND: Environmental exposure to toxicants poses high risk to develop reproductive and developmental chronic toxicity in man. Toluene is one of the commonest industrial agents whose exposure is attributed with potential to induce reproductive and developmental toxicity. Since they contaminate the immediate environment of air and water to which humans are exposed, its containment is of great public health importance. Conventional treatment modalities fail owing to the difficulty to detect these highly volatile agents in environment and human body. The peril of such hazardous exposures is evident only when irreversible structural and functional damages have incurred. In such instances, prevention gains an upper hand when compared to therapeutic interventions. Several natural compounds derived from medicinal herbs possess potential to curb toxicities induced by such xenobiotic agents. Among them Boerhavia diffusa Linn. is a widely distributed and common herb attributed with antitoxic potential and capability for antioxidant defence. A study was performed on the prophylactic efficacy of aqueous extract of B. diffusa in curbing toluene induced developmental toxicity in Drosophila melanogaster. METHODS: The study consisted of a preliminary phytochemical screening and HPTLC profiling of B. diffusa aqueous extract (BDAE). LC50 of toluene was assessed and a sublethal dose of 200ppm was fixed for the study. Four doses of BDAE; 25, 50, 100 and 200mg/ml designated as Low dose, medium dose 1, medium dose 2 and high dose was used for the study. The parameters used for the study included the determination of larval period, pupal period, percentage of egg hatching, morphometric analysis of egg, larvae, pupae and adults, fertility, fecundity, lifespan and levels of antioxidant enzymes such as catalase, glutathione-S-transferase and superoxide dismutase. RESULTS: The phytochemical and HPTLC characters were as per the pharmacopoeial standards. LC50 of toluene was found to be 430ppm in this study. BDAE at medium dose 2 and high dose significantly prevented the deterioration of reproductive and developmental toxicity parameters of larval period, pupal period, percentage of egg hatching, morphometric characters of larva, pupa and adult, fertility, fecundity and lifespan in drosophila. Also the drug significantly elevated the levels of antioxidant enzymes. CONCLUSION: Toluene exposure during lifetime is inevitable. B. diffusa, equipped with its rich active ingredients prevented toluene induced developmental and reproductive toxicity in Drosophila. This medicinal herb provides a ray of hope in preventing environmental toxin induced reproductive and developmental toxicity.

Neuroprotective and therapeutic effect of Cordyceps militaris on ischemia-induced neuronal death and cognitive impairments.

Cordyceps militaris is a type of fungus consumed by people all over the world and renowned for their nutritional benefits and herbal formulas to promote health and longevity. In the present study investigation was carried out to explore the therapeutic properties and neuroprotective effect of the C. militaris on ischemic brain neuronal injury, impairment of memory and learning in experimental rats induced by a global cerebral ischemia-reperfusion injury in WISTAR rats. Vascular Dementia with transient global brain injuries induced by a four-vessel occlusion (4-VO) in WISTAR rats. Further, donepezil (5 mg/kg) and C. militaris was (100 and 300 mg/kg, p.o.) were orally administered for 7 days in 4-VO WISTAR rats. C. militaris has the ability to improve memory impairments due to global cerebral ischemia and scopolamine-induced memory deterioration. Our present findings suggest that C. militaris may be a potential candidate for the neuroprotection of hippocampus and the recovery of various vascular dementia or neuroinflammatory disorders.

In vitro assessments of bone microcomputed tomography in an aged male rat model supplemented with Panax ginseng.

Recent research has confirmed that Panax ginseng (P. ginseng) has effect on cultured osteoblast of the mouse. In this study we aim to validate the usefulness of tibia quantification by correlating micro-computed tomographic (microCT) images with histology analysis in the aged male rats. A total of thirty - old male WISTAR rats were used and divided into ten 8 weeks rats and ten 112 weeks aged rats with vehicle and ten 112 weeks aged rats with P. ginseng (300 mg/kg/day). Daily oral administration of P. ginseng lasted for 8 weeks. Bone histomorphometric parameters and the trabecular bone microarchitectural properties of tibia were determined by microCT scan. MicroCT analysis showed significantly lower bone mineral density (BMD) and trabecular bone number in the aged group. Ginseng prevented total BMD decrease in the tibia induced by natural aging, which was accompanied by a significant decrease in skeletal remodeling. Furthermore, the aged group with ginseng was found to have a significantly higher osteoblast. In the blood biochemistry results, serum phosphorus, calcium, osteocalcin, T3, and T4 remained unchanged. The present study indicated that P. ginseng might be a potential alternative medicine for the prevention and treatment of natural aging-induced osteoporosis in human.

Effects of Panax ginseng C.A. Meyer extract on the offspring of adult mice with maternal immune activation.

To understand maternal immune activation (MIA) during prenatal development, the synthetic double­stranded RNA polyriboinosinic­polyribocytidylic acid [poly(I:C)] has been widely used in animal models to induce behavioral deficits similar to those in schizophrenia and other psychotic disorders. Panax ginseng C.A. Meyer (PG) extract is widely used to treat various kinds of nervous system disorders in Asia particularly China and Korea. The present study aimed to examine the effects of PG extract on MIA offspring using behavioral activity tests and protein expression analyses. Pregnant mice were exposed to poly(I:C) (5 mg/kg) or vehicle treatment on gestation day 9, and the resulting MIA offspring were subjected to vehicle or PG (300 mg/kg) treatment. In the acoustic startle response test, MIA­induced sensorimotor gating deficit was ameliorated by PG. The majority of behavioral parameters measured in the social interaction (non­aggressive or/and aggressive pattern), open field (number/duration of behavior) and forced swimming test (immobility behavior) were significantly altered in the MIA offspring. Western blot and immunohistochemical analyses of the medial prefrontal cortex indicated that the expression levels of certain neurodevelopmental proteins, including dihydropyrimidinase­related 2, LIM and SH3 domain 1, neurofilament medium, and discs large homolog 4, were decreased in the untreated MIA offspring, whereas PG treatment improved behavioral impairments and increased neurodevelopmental protein expression in MIA offspring. These results suggested that PG may be useful in neurodevelopmental disorder therapy, including psychiatric disorders such as schizophrenia, owing to its antipsychotic effects.

High-performance liquid chromatography analysis of phytosterols in Panax ginseng root grown under different conditions.

BACKGROUND: The Panax ginseng plant is used as an herbal medicine. Phytosterols of P. ginseng have inhibitory effects on inflammation-related factors in HepG2 cells. METHODS: Phytosterols (e.g., stigmasterol and ß-sitosterol) in the roots of P. ginseng grown under various conditions were analyzed using high-performance liquid chromatography. The P. ginseng roots analyzed in this study were collected from three cultivation areas in Korea (i.e., Geumsan, Yeongju, and Jinan) and differed by cultivation year (i.e., 4 years, 5 years, and 6 years) and production process (i.e., straight ginseng, red ginseng, and white ginseng). RESULTS: The concentrations of stigmasterol and ß-sitosterol in P. ginseng roots were 2.22-23.04 mg/g and 7.35-59.09 mg/g, respectively. The highest concentrations of stigmasterol and ß-sitosterol were in the roots of 6-year-old P. ginseng cultivated in Jinan (82.14 mg/g and 53.23 mg/g, respectively). CONCLUSION: Six-year-old white ginseng and white ginseng cultivated in Jinan containing stigmasterol and ß-sitosterol are potentially a new source of income in agriculture.

Antinociceptive effect of Valeriana fauriei regulates BDNF signaling in an animal model of fibromyalgia.

The genus Valeriana has been widely used in popular medicine for centuries, to treat sleep disorders, anxiety, epilepsy and insomnia. Recent studies have focused on the novel pharmacological effects of Valeriana fauriei Briq. (VF) species. Previous studies have attempted to determine the pharmacological functions of Valeriana in various human diseases, particularly with regards to its neuroprotective effects, and its ability to reduce pain and stress. The present study constructed an animal model of fibromyalgia (FM), which was induced by intermittent cold stress with slight modification. Subsequently, the study aimed to determine whether VF exerts antinociceptive effects on the FM­like model following oral administration of VF extracts. The effects of VF extracts on the FM model were investigated by analyzing behavioral activity, including pain, and detecting protein expression. In the behavioral analysis, the results of a nociception assay indicated that the pain threshold was significantly decreased in the FM group. Subsequently, western blotting and immunohistochemical analyses of the hippocampus demonstrated that the protein expression levels of brain­derived neurotrophic factor (BDNF) and phosphorylated­cAMP response element­binding protein were downregulated in the FM group. Conversely, VF restored these levels. These results suggested that the effects of VF extract on a model of FM may be associated with its modulatory effects on the BDNF signaling pathway in the hippocampus and medial prefrontal cortex. In conclusion, the mechanism underlying the protective effects of VF as a therapeutic agent against FM may involve the BDNF signaling pathway.

In-vitro antioxidative, antiinflammatory properties of Aurea helianthus leaf extract a Korean traditional medicinal plant.

The leaf of Aurea helianthus (A. helianthus Jinhuakui) is popularly used in China traditional medicine, however, scientific evidence on its antioxidant properties rarely studied. In this study, biological activities of A. helianthus leave's 80% ethanol extract (AHL) were investigated. The measured total polyphenol and flavonoid content of AHL was 184.24 ±â€¯5.01 mg GAE/g and 102.53 ±â€¯0.98 mg NAR/g. AHL showed the highest α, α-diphenyl-ß-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 98.30 ±â€¯0.18% at 1000 µg/mL. DPPH and ABTS radical scavenging activities significantly increased in a AHL concentration-dependent manner. AHL treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. AHL demonstrated strong anti-inflammatory activity that reduced NO production in LPS-stimulated RAW 264.7 cells. To test the potential protective effect of AHL, the antioxidant capacity, on the cell growth, viability of a human hepatoma cell (HepG2) and Raw 264.7 cell were investigated. AHL also enhanced cytotoxicity on the proliferation of HepG2 cells and was capable of inhibiting 56% against LPS at 400 µg/mL. The results of this study the potential of AHL as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, AHL may be used as a therapeutic approach to various inflammatory diseases.

Effect of Valeriana fauriei extract on the offspring of adult rats exposed to prenatal stress.

Exposing a pregnant female to stress is a risk factor for the development of psychiatric disorders in the offspring. In the present study, we examined the effects of an extract of Valeriana fauriei (VF) root (100 mg/kg/day, administered on postnatal days 35-56) on behavioral patterns as well as protein expression in the prefrontal cortex of the offspring of prenatally-stressed rats. Modified behavioral tests, including the forced swim test, the open field test, a social interaction test and the prepulse inhibition test were performed and many of the parameters were found to decrease in the offspring of the rats exposed to PNS compared with the offspring of the non-stressed rats. Western blot and immunohistochemical analyses of the prefrontal cortex revealed that the downregulation of several neurodevelopmental proteins in the offspring of rats dams exposed to PNS was reversed after treatment with VF extract. These findings demonstrate that the downregulation of several proteins in the prefrontal cortex of the offspring of prenatally­stressed rats may be associated with subsequent behavioral changes, and that these phenomena recovered following VF treatment. Our results suggest that VF decreases the incidence of prenatal stress related-psychiatric disorders, such as depression and schizophrenia.

Effects of Oriental Medicine Kyung-Ok-Ko on Uterine Abnormality in Hyperandrogenized Rats.

A traditional herbal prescription Kyung-Ok-Ko (KOK), composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquilaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in Oriental medicine as an invigorant for age-related diseases, such as amnesia and stroke. However, the beneficial value of KOK on uterine dysfunction related to hyperandrogenism is largely unknown. We investigated the effect of KOK (2.0 g/kg/day, per os) on endometrial abnormalities in a dehydroepiandrosterone (DHEA, subcutaneous)-induced polycystic ovary syndrome (PCOS) rat model. Preadministration of KOK significantly (p<0.05) decreased the elevated body weight, uterus weight, and endometrial thickness by PCOS induction, corresponding to reduced apoptosis and the infiltration of immune cells (CD4+ T cells, CD8+ T cells, and macrophages) in the endometrium. These results were associated with reduced mRNA expression of interleukin (IL)-1ß, IL-6, IL-8, and matrix metalloproteinase-3 and increased mRNA expression of IGF-ß1, transforming growth factor (TGF)-ß, TGF-ß1, and vascular endothelial growth factor in the uterus after DHEA injection. These multiple effects of KOK may synergistically prevent the development of endometrial abnormalities in DHEA-induced hyperandrogenism via anti-inflammatory action, indicating that KOK has preventive and therapeutic potential for suppressing PCOS.

An Alternative Triage Strategy Based on Preoperative MRI for Avoiding Trimodality Therapy in Stage IB Cervical Cancer.

PURPOSE: Adjuvant chemoradiation following primary surgery is frequently indicated in patients with stage IB cervical cancer. The aim of this study is to evaluate the role of a magnetic resonance imaging (MRI)-based strategy in avoiding trimodality therapy. MATERIALS AND METHODS: We retrospectively reviewed all patients with stage IB cervical cancer treated initially with primary surgery at Seoul National University Hospital. We suggest an alternative triage strategy in which the primary treatment modality is determined based on preoperative MRI findings. Using this strategy, primary surgery is only indicated when there is no evidence of parametrial involvement (PMI) and lymph node metastasis (LNM) in the MRI results; when there is evidence of either or both of these factors, primary chemoradiation is selected. Assuming that this strategy is applied to our cohort, we evaluate how the rate of trimodality therapy is affected. RESULTS: Of the 254 patients in our sample, 77 (30.3%) had at least one category 1 risk factor (PMI, LNM, positive resection margin) upon pathologic examination. If the MRI-based strategy had been applied to our cohort, 168 patients would have undergone primary surgery and 86 would have undergone primary chemoradiation. Only 25 patients (9.8%) would have required trimodality therapy based on an indication of at least one category 1 pathologic risk factor following radical hysterectomy. CONCLUSION: The inclusion of MRI in the decision-making process for primary treatment modality could have reduced the number of patients requiring trimodality therapy based on the indication of a category 1 risk factor from 30.3% to 9.8% in our cohort.

An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.

The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.

Influence of Panax ginseng on the offspring of adult rats exposed to prenatal stress.

The exposure of pregnant females to stress during a critical period of fetal brain development is an environmental risk factor for the development of schizophrenia in adult offspring. Schizophrenia is a group of common mental disorders of unclear origin, affecting approximately 1% of the global population, showing a generally young age at onset. In the present study, a repeated variable stress paradigm was applied to pregnant rats during the final week of gestation. The effects of an extract of Panax ginseng C.A. Meyer (PG) on rats exposed to prenatal stress (PNS) were investigated in terms of behavioral activity and protein expression analyses. In the behavioral tests, grooming behavior in a social interaction test, line-crossing behavior in an open-field test and swimming activity in a forced-swim test were decreased in the rats exposed to PNS compared with the non-stressed offspring; the changes in behavioral activity were reversed upon oral treatment with PG (300 mg/kg). Subsequently, western blot analysis and immunohistochemical analyses of the prefrontal cortex and hippocampus revealed that the downregulation of several neurodevelopmental genes which occurred following exposure to PNS was reversed upon treatment with PG. The current findings demonstrate that the downregulation of several genes following exposure to PNS may affect subsequent behavioral changes, and that these phenomena are reversed following treatment with PG during pregnancy. Our results suggest that oral treatment with PG reduces the incidence of psychiatric disorders, such as schizophrenia.

20 year experience of postoperative radiotherapy in IB-IIA cervical cancer patients with intermediate risk factors: impact of treatment period and concurrent chemotherapy.

OBJECTIVE: To compare the long-term clinical outcomes of adjuvant radiotherapy (RT) versus concurrent chemoradiotherapy (CCRT) in cervical cancer patients with intermediate risk factors. METHODS: Between 1990 and 2010, 110 cervical cancer patients with 2 or more intermediate risk factors (deep stromal invasion, lymphovascular space invasion, and large tumor size) underwent adjuvant RT (n=56) or CCRT (n=54) following radical surgery. Because CCRT had been performed since 2000, patients were divided into 3 groups regarding treatment period and the addition of chemotherapy, RT 1990-1999 (n=39), RT 2000-2010 (n=17) and CCRT 2000-2010 (n=54). Majority of concurrent chemotherapeutic regimens were carboplatin and paclitaxel (n=48). RESULTS: Five-year relapse-free survival (RFS) rates for RT 1990-1999, RT 2000-2010 and CCRT 2000-2010 were 83.5%, 85.6% and 93.8%, respectively. CCRT 2000-2010 had a significant decrease in pelvic recurrence (p=0.012) and distant metastasis (p=0.027). There were no significant differences in overall survival and RFS between RT 1990-1999 and RT 2000-2010. Acute grade 3 and 4 hematologic toxicities were more frequently observed in CCRT 2000-2010 (p<0.001). However, acute grade 3 and 4 gastrointestinal (GI) and chronic toxicities did not differ between the groups. CONCLUSIONS: This study shows that the addition of concurrent chemotherapy to postoperative RT in cervical cancer patients with intermediate risk factors may improve RFS without increasing acute GI and chronic toxicities, although hematologic toxicities increased significantly.

Matched-case comparison for the efficacy of neoadjuvant chemotherapy before surgery in FIGO stage IB1-IIA cervical cancer.

OBJECTIVE: To evaluate whether neoadjuvant chemotherapy before surgery (NCS) is more efficient than primary surgical treatment (PST) for improving clinical outcomes in FIGO stage IB1-IIA cervical cancer. METHODS: We conducted a matched-case comparison where 61 patients treated with NCS were matched to 183 treated with PST. We compared intermediate- and high-risk factors, the need of adjuvant radiotherapy, disease recurrence and survivals between NCS and PST. Patients with ≥2 intermediate- or ≥1 high-risk factors received adjuvant concurrent chemoradiation using cisplatin-based chemotherapy. RESULTS: NCS reduced more definitely intermediate- and high-risk factors than PST in stage IIA disease in spite of little difference of them in stage IB disease (large tumor size, 25% vs. 52.4%; deep stromal invasion, 57.1% vs. 82.1%; lymphovascular space invasion, 35.7% vs. 65.5%; parametrial invasion, 17.9% vs. 41.7%; p<0.05). Moreover, ≥2 intermediate-risk factors were less common in NCS than PST despite no difference of the number of high-risk factors between the 2 treatments, which decreased the need of adjuvant radiotherapy in patients with stage IIA disease who received NCS (46.4% vs. 84.5%, p<0.01). Although there were no differences in progression-free survival and disease recurrence between the 2 treatments, NCS led to poorer overall survival than PST in stage IIA disease with no difference of it in stage IB disease. CONCLUSIONS: The efficacy between NCS and PST may be similar in FIGO stage IB cervical cancer. However, NCS can lead to poor prognosis despite the reduction of intermediate-risk factors and the need of adjuvant radiotherapy in FIGO stage IIA disease.