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1.
BMC Cancer ; 23(1): 1059, 2023 Nov 03.
Article in English | MEDLINE | ID: mdl-37923987

ABSTRACT

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.


Subject(s)
Neoadjuvant Therapy , Rectal Neoplasms , Humans , Neoadjuvant Therapy/methods , Quality of Life , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Fluorouracil/therapeutic use , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/drug therapy , Chemoradiotherapy/methods , Neoplasm Staging
2.
J Surg Oncol ; 127(4): 668-677, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36515216

ABSTRACT

BACKGROUND AND OBJECTIVES: There is a paucity of evidence on the value of intraperitoneal chemotherapy (IPC) following cytoreductive surgery (CRS) for colorectal peritoneal metastasis. This study aimed to evaluate the association between mitomycin C-IPC and survival outcomes following CRS. METHODS: The institutional databases of two tertiary hospitals were reviewed to identify patients who underwent CRS for colorectal peritoneal metastasis. The outcomes of patients who underwent CRS without IPC were compared with those of patients who underwent CRS plus early postoperative intraperitoneal chemotherapy (EPIC) or CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC). The primary endpoints were cancer-specific survival (CSS), progression-free survival (PFS), and peritoneal PFS (P-PFS). RESULTS: In 149 patients with peritoneal metastasis alone, EPIC and HIPEC use was significantly associated with better CSS, PFS, and P-PFS in the multivariate analysis. CSS was also significantly associated with perioperative systemic chemotherapy. Among 42 patients with both peritoneal and extraperitoneal metastases, CSS was independently related to the completeness of cytoreduction score, location of extraperitoneal metastasis, and grade 3-4 complications. CONCLUSIONS: Mitomycin C-IPC after CRS was associated with better survival outcomes than CRS alone in patients with resectable peritoneal metastasis of colorectal cancer. This study found that IPC had beneficial effects regarding P-PFS in patients with both peritoneal and extraperitoneal metastases.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/surgery , Mitomycin , Cytoreduction Surgical Procedures , Retrospective Studies , Colorectal Neoplasms/pathology , Combined Modality Therapy , Chemotherapy, Cancer, Regional Perfusion , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate
3.
J Integr Med ; 19(3): 265-273, 2021 05.
Article in English | MEDLINE | ID: mdl-33349609

ABSTRACT

OBJECTIVE: SC-E3 is a polyherbal formula that contains five medicinal herbs used frequently in traditional herbal medicine. In our previous study, we demonstrated the antioxidant and anti-inflammatory effects of SC-E3. The present study examined the effects of SC-E3 in a mouse model of type-II collagen-induced arthritis (CIA). METHODS: In vivo, male DBA/1J mice were immunized by intradermal injection of bovine type-II collagen and complete or incomplete Freund's adjuvant, to induce arthritis. SC-E3 was orally administered daily for 23 days. In vitro, bone marrow-derived macrophages (BMMs) were treated with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL) in the absence or presence of SC-E3. RESULTS: Administrations of SC-E3 were found to have anti-arthritic effects in the joints of CIA mice, as evidenced by reduced paw swelling, bone erosion and deformation, inflammatory cell infiltration, and inflammation in synovial membrane. SC-E3 also reduced serum levels of tumor necrosis factor-α, interleukin-1ß, aspartate aminotransferase and alanine aminotransferase. Furthermore, tartrate-resistant acid phosphatase-positive osteoclast numbers in the joints were significantly lower in SC-E3-treated CIA mice than in CIA mice. In addition, the differentiations of BMMs to multinucleated osteoclasts induced by M-CSF and RANKL stimulation were dose-dependently reduced by SC-E3. CONCLUSION: These results suggest that SC-E3 possesses substantial anti-arthritic activity because it inhibits pro-inflammatory cytokines and osteoclastogenesis, and that SC-E3 has potential therapeutic use for the treatment of rheumatoid arthritis.


Subject(s)
Arthritis, Experimental , Arthritis, Rheumatoid , Animals , Arthritis, Experimental/drug therapy , Arthritis, Rheumatoid/drug therapy , Cattle , Disease Models, Animal , Male , Mice , Mice, Inbred DBA , Osteoclasts
4.
J Anim Sci Technol ; 62(4): 485-494, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32803181

ABSTRACT

Limiting amino acids (AAs) for milk production in dairy cows fed on a concentrate diet of corn grain and soybean meal was evaluated in this study. Four lactating and multiparous Holstein cows (in third or fourth parities, with an average body weight of 633 ± 49.2 kg), 8 to 9 weeks into their lactation period, were used in a 4 × 4 Latin square design. The experiment comprised four dietary treatments: (1) no intravenous infusion (control); (2) control plus intravenous infusion of an AA mixture of 6 g/d methionine, 19.1 g/d lysine, 13.8 g/d isoleucine, and 15.4 g/d valine (4AA); (3) control plus intravenous infusion of the AA mixture without methionine (no-Met); and (4) control plus intravenous infusion of the AA mixture without lysine (no-Lys). All animals were fed on a controlled diet (1 kg/d alfalfa hay, 10 kg/d silage, 14 kg/d concentrate mixture, ad libitum timothy hay). The AA composition of the diet and blood were determined using an automatic AA analyzer. Milk composition (protein, fat, lactose, urea nitrogen, and somatic cell counts) was determined using a MilkoScan. The results showed that feed intake for milk production did not differ from that of intravenous infusion using a limiting AA mixture. The 4AA treatment numerically had the highest milk yield (32.4 kg/d), although there was no difference when compared with the control (31.2 kg/d), no-Met (31.3 kg/d), and no-Lys (31.7 kg/d) treatments. The concentration of AAs in blood plasma of cows in all treatments, mainly isoleucine and valine, increased significantly compared with that of control. The no-Met treatment increased (p < 0.05) the concentration of lysine in the blood relative to the control and no-Lys treatments, whereas the no-Lys treatment increased (p < 0.05) the concentration of methionine relative to the control and no-Met treatments. In conclusion, milk production increased when feeding 10 g/d methionine to the cows, together with their concentrate diet of corn grain and soybean meal.

5.
Trials ; 21(1): 628, 2020 Jul 08.
Article in English | MEDLINE | ID: mdl-32641081

ABSTRACT

BACKGROUND: Current guidelines recommend the prescription of immune-enriched oral nutritional supplements for malnourished patients before major gastrointestinal surgery. However, the benefit of preoperative immunonutrition is still controversial. This randomized controlled trial aims to evaluate the effect of preoperative immunonutrition on the outcomes of surgery for colon cancer. METHODS/DESIGN: Patients with primary colon cancer will be included as study participants after screening. They will be randomly assigned (in a ratio of 1:1) to receive preoperative immunonutrition added to the normal diet (experimental arm) or consume normal diet alone (control arm). Patients in the experimental arm will receive oral supplementation (400 mL/day) with arginine and ω-3 fatty acids for 7 days before elective surgery. The primary endpoint is the rate of infectious complications, while the secondary endpoints are postoperative complication rate, change in body weight, length of hospital stay, and nature of fecal microbiome. The authors hypothesize that the rate of infectious complications would be 13% in the experimental arm and 30% in the control arm. With a two-sided alpha of 0.05 and a power of 0.8, the sample size is calculated as 176 patients (88 per arm). DISCUSSION: Although there have been many studies demonstrating significant benefits of preoperative immunonutrition, these were limited by a small sample size and potential publication bias. Despite the recommendation of immunonutrition before surgery in nutritional guidelines, its role in reduction of rate of infectious complications is still controversial. This trial is expected to provide evidence for the benefits of administration of preoperative immunonutrition in patients with colon cancer. TRIAL REGISTRATION: Clinical Research Information Service KCT0003770 . Registered on 15 April 2019.


Subject(s)
Colonic Neoplasms/surgery , Dietary Supplements , Elective Surgical Procedures/adverse effects , Postoperative Complications/prevention & control , Preoperative Care/methods , Arginine/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Humans , Length of Stay , Malnutrition , Prospective Studies , Randomized Controlled Trials as Topic
6.
Chin Med ; 14: 43, 2019.
Article in English | MEDLINE | ID: mdl-31624493

ABSTRACT

BACKGROUND: Trichosanthis semen, the seeds of Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, has long been used in Korean medicine to loosen bowels and relieve chronic constipation. Although the fruits and radixes of this medicinal herb and their constituents have been reported to exhibit therapeutic effects in various cancers, the anti-cancer effects of its seeds have been relatively less studied. In this study, we investigated the effects of an ethanolic extract of T. kirilowii seeds (TKSE) against colorectal cancer and its mechanism. METHODS: The anti-tumor effects of the TKSE were evaluated in HT-29 and CT-26 colorectal cancer cells and in a CT-26 tumor-bearing mouse model. RESULTS: TKSE suppressed the growth of HT-29 and CT-26 cells (both colorectal cancer cell lines) and the cytotoxic effect of TKSE was greater than that of 5-fluorouracil (5-Fu) in HT-29 cells. TKSE significantly induced mitochondrial membrane potential loss in HT-29 and CT-26 cells and dose-dependently inhibited Bcl-2 expression and induced the cleavages of caspase-3 and PARP. In particular, TKSE at 300 µg/mL induced nuclear condensation and fragmentation in HT-29 cells. Furthermore, TKSE dose-dependently inhibited activations of the Akt/mTOR and ERK pathways, and markedly induced the phosphorylation of AMPK. An AMPKα inhibitor (compound C) effectively blocked the TKSE-induced mitochondrial dysfunction. In addition, TKSE attenuated the hypoxia-inducible factor-1α/vascular endothelial growth factor signaling pathway in HT-29 cells under hypoxic-mimic conditions and inhibited migration and invasion. Oral administration of TKSE (100 or 300 mg/kg) inhibited tumor growth in a mouse CT-26 allograft model but was not as effective as 5-Fu (the positive control), which was administered intraperitoneally. In the same model, 5-Fu caused significant body weight loss, but no such loss was observed in TKSE-treated mice. CONCLUSION: Taken together, these results suggest TKSE has potent anti-tumor effects which might be partly due to the activation of AMPK, and the induction mitochondrial-mediated apoptosis in colorectal cancer cells. These findings provide scientific evidence supporting the potential use of TKSE as a complementary and alternative medicine for the treatment of colorectal cancer.

7.
Mol Med Rep ; 19(3): 2087-2096, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30747232

ABSTRACT

Dendropanax morbifera (D. morbifera), known as Dendro, means 'omnipotent drug' (Panax), and has been called the panacea tree. Various studies on D. morbifera are currently ongoing, aiming to determine its medicinal uses. The present study investigated the anti­inflammatory effects and underlying mechanism of a natural extract of D. morbifera leaves (DPL) in lipopolysaccharide (LPS)­stimulated RAW264.7 macrophages. In the present study, the following assays and models were used: MTT assay, nitric oxide (NO) assay, western blotting, ELISA and mouse models of atopic dermatitis. DPL extract markedly reduced the production of NO, inducible NO synthase and interleukin­6, as well as the nuclear translocation of nuclear factor­κB (NF­κB). Additionally, the LPS­induced activation of extracellular signal­regulated kinase 1/2 (ERK1/2), P38 and c­Jun N­terminal kinase (JNK) was suppressed by DPL extract. Taken together, these results indicate that NF­κB, ERK1/2, P38 and JNK may be potential molecular targets of DPL extract in the LPS­induced inflammatory response. Subsequently, the present study investigated the effects of DPL extract in a 2,4­dinitrochlorobenzene­induced atopic dermatitis mouse model. Ear thickness, serum immunoglobulin E levels and histological analysis revealed that the DPL extract was effective in attenuating the inflammatory response. These results indicate that DPL extract has anti­inflammatory potential and may be developed as a botanical drug to treat atopic dermatitis.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Araliaceae/chemistry , Dermatitis, Atopic/drug therapy , Lipopolysaccharides/immunology , Macrophages/drug effects , Plant Extracts/therapeutic use , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Disease Models, Animal , Female , Macrophages/immunology , Macrophages/pathology , Mice , Mice, Inbred BALB C , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , RAW 264.7 Cells
8.
Article in English | MEDLINE | ID: mdl-30581485

ABSTRACT

Selaginella Herba is the dried, aerial part of Selaginella tamariscina (P.Beauv.) Spring and has been used to treat amenorrhea, abdominal pain, headaches, and hematuria in Korea. However, scientific evidence regarding the anti-inflammatory activity and action mechanism of Selaginella tamariscina is lacking. Thus, the present study was performed to investigate the anti-inflammatory and antioxidant activities of Selaginella tamariscina ethanol extract (STE) against lipopolysaccharide (LPS)-induced inflammatory responses and identify the molecular mechanism responsible. STE was prepared by heating in 70% ethanol and its quality was confirmed by HPLC. STE dose-dependently inhibited the productions of inflammatory mediators (NO and PGE2) and proinflammatory cytokines (IL-1ß and IL-6) in LPS-stimulated RAW 264.7 cells. STE markedly suppressed the phosphorylations of MAPKs, IκB-α, and NF-κB and the nuclear translocation of NF-κB induced by LPS stimulation. In addition, STE exhibited good free radical scavenging activity and prevented ROS generation by LPS. STE also upregulated the expression of Nrf2 and HO-1 and promoted the nuclear translocation of Nrf2. Taken together, STE was found to have anti-inflammatory and antioxidant effects on RAW 264.7 macrophages and the mechanism appeared to involve the MAPK, NF-κB, and Nrf2/HO-1 signaling pathways. These results suggest that STE might be useful for preventing or treating inflammatory diseases and provide scientific evidence that supports the developments of herbal prescriptions or novel natural products.

9.
J Vis Exp ; (142)2018 12 09.
Article in English | MEDLINE | ID: mdl-30582585

ABSTRACT

Ischemia followed by reperfusion of cerebral blood flow after a stroke leads to the death of nerve cells and loss of brain tissue. The most commonly used animal model for studying stroke is the middle cerebral artery occlusion (MCAO) model. Previous research studies have reported different infarct sizes even when the same experimental animal species was used under similar MCAO conditions. Therefore, we developed an improved experimental method to address this discrepancy. Mice were subjected to MCAO using a filament as the occlusion material to mimic human stroke conditions and filament thickness was optimized to establish more reproducible infarction volume. Mice treated with a methanol extract of Glycyrrhizae Radix et Rhizome (GRex) following stroke induction showed a significantly decreased total infarction volume and increased number of surviving cells relative to the untreated control group. This modified experimental protocol successfully and reproducibly demonstrated the beneficial effect of GRex on ischemic stroke.


Subject(s)
Glycyrrhiza/classification , Infarction, Middle Cerebral Artery/drug therapy , Plant Extracts/pharmacology , Animals , Disease Models, Animal , Male , Mice , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Neuroprotective Agents/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Rhizome/chemistry
10.
Chem Biol Interact ; 261: 108-117, 2017 Jan 05.
Article in English | MEDLINE | ID: mdl-27871897

ABSTRACT

Sauchinone is a pharmacologically active compound isolated from Saururus chinensis, which has been used as a traditional Oriental medicine to treat fever, jaundice, and various inflammatory diseases. In this study, we investigated the effect of sauchinone against hepatocellular carcinoma (HCC) and sought to elucidate the mechanism involved. Cell viability was measured by an MTT assay. Cell cycle distributions and the mitochondrial membrane potential were analyzed using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Protein and mRNA levels were assessed by western blot and real-time PCR, respectively. Malignant properties were investigated by a wound healing migration assay and invasion assay. Sauchinone suppressed the proliferation of human HCC cells in a dose-dependent manner. Moreover, it induced the G0/G1 phase cell cycle arrest and mitochondrial dysfunction and then triggered the apoptosis by activating the JNK/p38 pathway in Huh-7 cells. In addition, sauchinone induced the activation of the AMP-activated protein kinase (AMPK) pathway, and compound C (an AMPK inhibitor) blocked the sauchinone-induced mitochondrial dysfunction. The AMPK activation by sauchinone inhibited the phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream targets, such as ribosomal protein S6 kinase 1 and eIF4E-binding protein 1. Furthermore, sauchinone attenuated key proangiogenic factors, including hypoxia-inducible factor-1α, vascular endothelial growth factor, and plasminogen activator inhibitor-1, resulting in decreased migration and invasion of HCC cells. These results provide evidence for sauchinone to be considered as a potent anticancer agent by targeting of the AMPK-mTOR pathway in HCC.


Subject(s)
AMP-Activated Protein Kinases/metabolism , Antineoplastic Agents/therapeutic use , Benzopyrans/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/enzymology , Dioxoles/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/enzymology , Signal Transduction/drug effects , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Benzopyrans/pharmacology , Carcinoma, Hepatocellular/pathology , Cell Cycle/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Dioxoles/pharmacology , Enzyme Activation/drug effects , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Liver Neoplasms/pathology , Neoplasm Invasiveness , Vascular Endothelial Growth Factor A/metabolism
11.
Photodermatol Photoimmunol Photomed ; 32(1): 34-43, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26479265

ABSTRACT

BACKGROUND: Light-emitting diode (LED) phototherapy and water bath therapy have beneficial effect on atopic dermatitis (AD)-like skin disease. However, not all current treatments work well and alternative therapies are need. The contribution of combination therapy with low-dose 850 nm LED and water bath was investigated on dermatophagoides farina (Df)-induced dermatitis in NC/Nga mice. METHODS: Low-dose LED (10, 15, and 20 J/cm(2) ) irradiation, water bath (36 ± 1°C) were administered separately and together to the Df-induced NC/Nga mice in acrylic jar once a day for 2 weeks. RESULTS: Combined therapy with low-dose LED therapy and water bath therapy significantly ameliorated the development of AD-like skin lesions. These effects were correlated with the suppression of total IgE, NO, histamine, and Th2-mediated immune responses. Furthermore, combination therapy significantly reduced the infiltration of inflammatory cells and the induction of thymic stromal lymphopoietin (TSLP) in the skin lesions. The beneficial therapeutic effects of this combination therapy might regulate by the inhibition of various immunological responses including Th2-mediated immune responses, inflammatory mediators such as IgE, histamine, and NO, as well as inflammatory cells. CONCLUSIONS: The combination therapy of LED and water bath might be used as an efficacious, safe, and steroid-free alternative therapeutic strategy for the treatment of AD.


Subject(s)
Baths , Dermatitis, Atopic/therapy , Phototherapy , Animals , Cytokines/immunology , Dermatitis, Atopic/immunology , Dermatitis, Atopic/pathology , Immunoglobulin E/immunology , Male , Mice , Nitric Oxide/immunology , Th2 Cells/immunology , Th2 Cells/pathology , Thymic Stromal Lymphopoietin
12.
Eur J Pharmacol ; 756: 43-51, 2015 Jun 05.
Article in English | MEDLINE | ID: mdl-25796200

ABSTRACT

Although cyclosporine A (CsA) is a potent immunomodulating agent and is commonly used as a systemic agent for the management of psoriasis patients, current clinical treatments are not always effective due to the clinical inefficacy of low-doses and numerous harmful effects of higher doses. Currently, the combined use of two other systemic drugs often has better therapeutic efficacy and is safer than low or high dose of a single drug. Glucosamine (Glu) also has immunomodulatory properties for autoimmune diseases. The aims of our study were to investigate the therapeutic efficacy of Glu in combination with low-dose CsA on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and to determine its immunomodulatory mechanism. We found that combined treatment with Glu (300 mg/kg) and low-dose (10 or 20mg/kg) CsA strongly ameliorated the development of psoriasis-like skin lesions and reduced the levels of Th1 cytokine (TNF-α) and Th17 cytokines (IL-17, IL-22, and IL-23) in the serum and dorsal skin. Histological findings also showed that the thickening of epidermis, stratum corneum, and inflammatory cell infiltration. Particularly, these combined treatments increased the number of CD4(+)CD25(+) regulatory T (Treg) cells in splenic. These results suggest that use of a combination of each drug might be used as an efficacious and safe alternative therapeutic strategy, as well as may provide an immunomodulatory approach for T cell-mediated autoimmune diseases, including psoriasis.


Subject(s)
Aminoquinolines/adverse effects , Cyclosporine/pharmacology , Glucosamine/pharmacology , Immunomodulation/drug effects , Psoriasis/drug therapy , Psoriasis/immunology , Animals , Cyclosporine/therapeutic use , Dermatitis/drug therapy , Dermatitis/etiology , Dermatitis/immunology , Dermatitis/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Glucosamine/therapeutic use , Imiquimod , Mice , Mice, Inbred C57BL , Organ Size/drug effects , Psoriasis/chemically induced , Psoriasis/pathology , Spleen/drug effects , Spleen/pathology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology
13.
J Med Entomol ; 51(1): 68-75, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24605455

ABSTRACT

Aedes (Stegomyia) aegypti (L.) and Aedes (Stegomyia) albopictus (Skuse) larvae rely on oxidases to reduce toxicity of water soluble toxins from some senescent tree leaf infusions. The mortality of third instar Ae. aegypti larvae in live oak and pin oak leaf infusions increased significantly in the presence of piperonyl butoxide (PBO), a broad inhibitor of cytochrome P450s (CYPs). In contrast, PBO treatment did not increase mortality in water controls or infusions of northern red oak or sugar maple leaf infusions for Ae. aegypti larvae. A similar pattern was observed for Ae. albopictus larvae, that is, an increase in mortality when CYPs were inhibited in live oak leaf infusions and no increase in sugar maple leaf infusions or water controls. However, the fresh live oak leaf infusion (5 d old) was the most toxic infusion to Ae. aegypti, but appeared less toxic to Ae. albopictus than the older infusions. A direct comparison of survival between the two Aedes species revealed Ae. aegypti exhibited a greater mortality than Ae. albopictus in PBO-treated live oak leaf infusions. These findings suggest that toxic components of some leaf litter in larval habitats may impose cryptic energy costs (detoxification).


Subject(s)
Acer/toxicity , Aedes/enzymology , Oxidoreductases/metabolism , Plant Preparations/toxicity , Quercus/toxicity , Animals , Insect Proteins/metabolism , Larva/enzymology , Piperonyl Butoxide , Plant Leaves/toxicity
14.
Pharmacol Biochem Behav ; 118: 10-5, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24398147

ABSTRACT

Recently, we reported that Alpinia katsumadai (AK) has anti-nociceptive activity in vivo and that cardamonin (CDN) from AK suppresses the activity and expression of transglutaminase-2 (Tgase-2). However, it remains unknown whether CDN contributes to the anti-nociceptive activities of AK in vivo. We examined the anti-inflammatory effects of CDN in MG63 osteoblast-like cells and Raw264.7 macrophage-like cells treated with interleukin-1ß treatment. CDN suppressed the expression of Tgase-2, cyclooxygenase-2 (COX-2), and p65 (nuclear factor-κB) in a concentration-dependent manner, and restored the expression of IκB in MG63 and Raw264.7 cells. However, CDN did not inhibit the activity of COX-2. Gene silencing of Tgase-2 reduced the COX-2 expression in MG63 cells. Phenylbenzoquinone (PBQ)-induced writhing, carrageenan-induced hyperalgesia, and rota-rod test were used to evaluate the anti-nociceptive activity in vivo. CDN (3-30 mg/kg, orally administered) significantly inhibited PBQ-induced writhing. CDN also produced a significant, dose-dependent increase in the withdrawal response latencies in carrageenan-induced hyperalgesia. The effects of CDN on PBQ-induced writhing were not caused by impaired motor functions. These results suggest that CDN might be helpful in controlling the pain from inflammatory diseases.


Subject(s)
Analgesics/pharmacology , Chalcones/pharmacology , Cyclooxygenase 2 Inhibitors/pharmacology , GTP-Binding Proteins/antagonists & inhibitors , Transglutaminases/antagonists & inhibitors , Alpinia , Animals , Benzoquinones/toxicity , Carrageenan/toxicity , Cell Line , Cyclooxygenase 2/genetics , GTP-Binding Proteins/genetics , Gene Expression/drug effects , Humans , Male , Medicine, Korean Traditional , Mice , Mice, Inbred ICR , Pain/drug therapy , Plants, Medicinal , Protein Glutamine gamma Glutamyltransferase 2 , RNA, Small Interfering/genetics , Rats , Rats, Sprague-Dawley , Transglutaminases/genetics
15.
J Dermatol Sci ; 72(2): 142-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23810774

ABSTRACT

BACKGROUND: Light emitting diode (LED) phototherapy is an effective alternative for the treatment of inflammatory skin disorders. Tacrolimus (FK-506) is a potent immunomodulating agent, which has been used to treat AD. Combination therapy is often used in the treatment of AD to improve therapeutic efficacy or to reduce the dose of each drug. OBJECTIVE: To investigate the therapeutic efficacy of monotherapy with either 850nm LED phototherapy or low-dose FK-506, and combination therapy in Dermatophagoides farina (Df)-induced AD-like skin lesions in NC/Nga mice. METHODS: The Df-induced NC/Nga mice with a clinical score of 7 were used for treatment with LED (10 and 25J/cm(2)) alone, low-dose FK-506 (1mg/kg) or in combination. The synergistic effects of combined therapy were evaluated by dermatitis scores, skin histology, skin barrier function, and immunological parameters, such as IgE, NO, Th2-mediated cytokines and chemokines. RESULTS: Combination therapy with 850nm (25J/cm(2)) LED and low-dose FK-506 showed a significant reduction in the severity of skin lesions. Combined therapy decreased in the serum level of IgE, NO, and in the splenic level of Th2-mediated cytokines and chemokines. Combination therapy significantly also reduced the inflammatory cellular infiltrate into the skin lesions. Moreover, combination therapy led to recovery of skin barrier function in the skin lesions. CONCLUSIONS: The use of combination of LED phototherapy and low-dose immunosuppressant improved Df-induced AD-like skin lesions in an NC/Nga mouse model by dominantly reducing IgE, NO, suppressing Th2-mediated immune responses, and inhibiting inflammatory cells, as well as improving skin barrier function.


Subject(s)
Dermatitis, Atopic/therapy , Dermatophagoides farinae/metabolism , Phototherapy/methods , Tacrolimus/administration & dosage , Animals , Chemokines/metabolism , Combined Modality Therapy/methods , Cytokines/metabolism , Dermatitis, Atopic/parasitology , Humans , Immunoglobulin E/blood , Immunosuppressive Agents/administration & dosage , Inflammation , Light , Male , Mice , Nitric Oxide/blood , Skin/metabolism , Spleen/metabolism , Th2 Cells/metabolism
16.
Asian-Australas J Anim Sci ; 26(9): 1289-94, 2013 Sep.
Article in English | MEDLINE | ID: mdl-25049911

ABSTRACT

This study evaluated the in vitro effect of medicinal plant extracts on ruminal methanogenesis, four different groups of methanogens and ruminal fermentation characteristics. A fistulated Holstein cow was used as a donor of rumen fluid. Licorice and mugwort extracts (Glycyrrhiza uralensis and Artemisia capillaris, 0.5% and 1% of total substrate DM, respectively), previously used as folk remedies, were added to an in vitro fermentation incubated with buffered-rumen fluid. Total gas production in Glycyrrhiza uralensis extract treatment was not significantly different between treatments (p<0.05) while total gas production in the Artemisia capillaris extract treatment was lower than that of the control. Artemisia capillaris extract and Glycyrrhiza uralensis extract reduced CH4 emission by 14% (p<0.05) and 8% (p<0.05), respectively. Ciliate-associated methanogens population decreased by 18% in the medicinal plant extracts treatments. Medicinal plant extracts also affected the order Methanobacteriales community. Methanobacteriales diversity decreased by 35% in the Glycyrrhiza uralensis extract treatment and 30% in the Artemisia capillaris extract treatment. The order Methanomicrobiales population decreased by 50% in the 0.5% of Glycyrrhiza uralensis extract treatment. These findings demonstrate that medicinal plant extracts have the potential to inhibit in vitro ruminal methanogenesis.

17.
J Med Food ; 13(3): 673-80, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20521990

ABSTRACT

Ultraviolet (UV) light is a physical carcinogen, and UV irradiation from sunlight has negative effects on human skin. UVB-induced inflammation is linked to excessive induction of various inflammatory cytokines/chemokines in many types of cells, including keratinocytes. The purpose of this study was to investigate the anti-inflammatory effect of water extract of Zingiber officinale, gingerol, and shogaol on UVB-induced skin damage in the human keratinocyte cell line HaCaT and C57BL/6 mice. To test for an effective compound to protect against inflammation in UV-damaged skin, we prepared a water extract of ginger rhizomes and examined the effects of Z. officinale, gingerol, and shogaol on cell viability and cytokine/chemokine production in UV-irradiated HaCaT cells. We also investigated the in vivo relevance of these findings in C57BL/6 mice using hematoxylin and eosin staining and cytokine measurements. A water extract of Z. officinale, gingerol, and shogaol inhibited production of cytokines in UVB-irradiated HaCaT cells effectively. Treatment with Z. officinale attenuated UVB-induced hyperplasia, infiltration of leukocytes, and dilation of blood vessels in the dermis of mice. Z. officinale, gingerol, and shogaol show potential as anti-inflammatory agents to protect skin against UVB irradiation damage.


Subject(s)
Keratinocytes/drug effects , Keratinocytes/immunology , Plant Extracts/pharmacology , Radiation-Protective Agents/pharmacology , Skin/drug effects , Skin/immunology , Zingiber officinale/chemistry , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cell Survival/radiation effects , Keratinocytes/radiation effects , Male , Mice , Mice, Inbred C57BL , Plant Extracts/administration & dosage , Radiation-Protective Agents/administration & dosage , Skin/radiation effects , Ultraviolet Rays
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