• 제목/요약/키워드: therapeutic agents

검색결과 794건 처리시간 0.024초

Intravenous Mesenchymal Stem Cell Administration Modulates Monocytes/Macrophages and Ameliorates Asthmatic Airway Inflammation in a Murine Asthma Model

  • Mo, Yosep;Kang, Sung-Yoon;Bang, Ji-Young;Kim, Yujin;Jeong, Jiung;Jeong, Eui-Man;Kim, Hye Young;Cho, Sang-Heon;Kang, Hye-Ryun
    • Molecules and Cells
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    • 제45권11호
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    • pp.833-845
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    • 2022
  • Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

Recent Progress in Immunotherapy for Gastric Cancer

  • Jeesun Yoon;Tae-Yong Kim;Do-Youn Oh
    • Journal of Gastric Cancer
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    • 제23권1호
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    • pp.207-223
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    • 2023
  • Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action

  • Yibo Zhang;Xuanlei Zhong;Zhichao Xi;Yang Li;Hongxi Xu
    • Journal of Ginseng Research
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    • 제47권2호
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    • pp.183-192
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    • 2023
  • Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

  • Kyung-il Kim;Rajib Hossain;Xin Li;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • 제31권5호
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    • pp.484-495
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    • 2023
  • Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

염증성 질환에 대한 Crocin의 치료 효과 (Therapeutic Effect of Crocin in Inflammatory Diseases)

  • 김영희
    • 생명과학회지
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    • 제34권2호
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    • pp.138-144
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    • 2024
  • Crocin은 여러 가지 요리에 향미와 색깔을 주는 치자 열매나 사프란에 함유되어 있는 적노란색의 수용성 색소이다. 사프란과 치자는 전통의학 분야에서 부종, 해열, 해독 작용이 있어 바이러스성 간염, 식도염, 관상동맥심장병, 신경쇠약, 불면증, 퇴행성 신경질환, 호흡기 질환, 비뇨기 질환 등을 치료하는데 사용되어 왔다. Crocin (C44H64O24)은 카로테노이드의 복합체로, dicarboxylic acid crocetin과 disaccharide gentiobiose로 이루어진 diester이다. Crocin은 혈액학적인, 병리학적인 독성이나 유전독성이 없다. 현재까지 수많은 생체 내 및 생체 외 연구들을 통해 Crocin의 생물학적인 약리작용이 밝혀지고 있다. 본 총설에서는 염증성 장질환, 위염, 천식, 동맥경화, 류머티스 관절염, 다발성 경화증, 당뇨, 알츠하이머병, 파킨슨병, 우울증 등의 염증 관련 질환에서 Crocin의 보호 효과를 요약한다. Crocin은 다양한 작용 기전을 통해 항염, 항산화, 세포 자살 방지 기능을 함으로써 이들 질환을 개선하는 것으로 추론된다.

Signal Transduction Events Elicited by Natural Products: Role of MAPK and Caspase Pathways in Homeostatic Response and Induction of Apoptosis

  • Kong, Ah-Ng Tony;Yu, Rong;Chen, Chi;Mandlekar, Sandhya;Primiano, Thomas
    • Archives of Pharmacal Research
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    • 제23권1호
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    • pp.1-16
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    • 2000
  • Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many man become important therapeuitc drugs of the future.

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Sarcoma 180 유발후(誘發後)의 생쥐의 생존(生存) 시간(時間)에 대(對)한 Cyclophosphamide, Corynebacterium Parvum 및 Tubercin-3의 단독(單獨) 및 병합역여(倂合役與)의 영향(影響) (Survival Effect on Sarcoma 180 bearing Mice after the Treatment with Tubercin-3, Corynebacterium parvum anad Cyclophosphamide alone and in combination)

  • 김희태;김인수;서대규
    • 대한약리학회지
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    • 제17권1호
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    • pp.41-46
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    • 1981
  • Eighty of Sarcoma 180 bearing mice, averaging 30 gm of body weight, were divided into eight groups of animals receiving Saline as the control, Corynebacterium parvum, Tubercin-3 and Cyclophosphamide alone and Cyclophosphamide combined with C. parvum, with Tubercin-3 and with both C. parvum and Tubercin-3 and Tubercin-3 combined with C. parvum respectively. Treatment was initiated 4.8 hours after tumor implantation and repeated three times once a day. Doses were suspended or dissolved in 0.2 ml of Saline: 1.4 mg of C. parvum: 0.5 micrograms of Tubercin-3; and 2.7 mg of Cyclophosphamide either in alone or in combination. All the agents given were administered subcutaneously but Cyclophosphamide was given intraperitoneally. The observation on the general conditions of animal took place twice a day following the treatment until the time of death after tumor implantation was determined. Average survival days in each group were as follows: In Control, Saline (11.2 days), C. parvum (14.8 days), Tubercin-3 (16.7 days), Cyclophosphamide(18.7 days). In combination therapy, Cyclophosphamide with C. parvum(22.8 days) with Tubercin-3 (26.9 days). Cyclophosphamide with both C. parvum an Tubercin-3, however, was somewhat longer than in Cyclophosphamide alone but shorter than in combined with either one of C. parvum or Tubercin-3. Finally, in combination with immunotherapeutic agents, Tubercin-3 and C. parvum each other it (8.2 days) was shorter even than Control. Life span of host is, in generally, inversely related to the number of malignant cells and conclusively, the therapeutic potentiation was reflected to be extended survival in combined treatment of a chemotherapeutic Cyclophosphamide with either one of immunotherapeutics, Tubercin-3 or C. parvum. Tubercin-3 and C. parvum in combination, however, appeared to be antagonistic each other.

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Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

  • Heidari, Reza;Esmailie, Neda;Azarpira, Negar;Najibi, Asma;Niknahad, Hossein
    • Toxicological Research
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    • 제32권2호
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    • pp.133-140
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    • 2016
  • Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

Pheophytin Content and Cytotoxicity of Silkworm Feces Against Jurkat Cells According to Dry Method and Storage Period

  • Ahn, Mi-Young;Kim, Iksoo;Ryu, Kang-Sun;Kim, Jin-Won;Lee, Heui-Sam;Lee, Pyeong-Jae;Ko, Si-Hwan;Lee, Won-Young
    • International Journal of Industrial Entomology and Biomaterials
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    • 제8권2호
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    • pp.135-138
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    • 2004
  • In order to find potential anticancer agents, we extracted pheophytin from silkworm feces according to various dry and storage methods such as sun dry, shade dry, fresh freezing dry and freezing dry after freezing storage (for 1∼3 years). The pheophytin extracts, mainly 10-hydroxypheophytin a, little b, of various storage silkworm feces were analyzed by reversed-phase high-performance liquid chromatography with photodiode array and fluorescence detection. The content of those pheophytih in old silkworm for 3 years (freezing storage and freezing dried in use, or freezing dried and cold storage) was better than others. The cytotoxicity of the pheophytin extracts and ethanol extracts of various storage silkworm feces were measured using Jurkat cells originated from human leukemia, using dye uptake assay (MTT) in order to find effective photodynamic therapeutic agents. The anticancer activity of those pheophytin extracts in various storage methods showed little difference among them. But ethanol extracts of fresh freezing dried silkworm in the current year was good cytotoxic activity than those of any other silkworm feces. With regards to these results, fresh ethanol extracts of silkworm feces were better than old ones. On the other hands, the pheophytin extracts of old silkworm feces contained the highest percentage of pheophytin content and showed good cytotoxicity against cancer cells by changing the pheophytin into pheophobide in the degradative process.

Burkholderia Cepacia Causing Nosocomial Urinary Tract Infection in Children

  • Lee, Ki Wuk;Lee, Sang Taek;Cho, Heeyeon
    • Childhood Kidney Diseases
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    • 제19권2호
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    • pp.143-147
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    • 2015
  • Purpose: Burkholderia cepacia is an aerobic, glucose-non-fermenting, gram-negative bacillus that mainly affects immunocompromised and hospitalized patients. Burkholderia cepacia has high levels of resistance to many antimicrobial agents, and therapeutic options are limited. The authors sought to analyze the incidence, clinical manifestation, risk factors, antimicrobial sensitivity and outcomes of B. cepacia urinary tract infection (UTI) in pediatric patients. Methods: Pediatric patients with urine culture-proven B. cepacia UTI between January 2000 and December 2014 at Samsung Medical Center, a tertiary referral hospital in Seoul, Republic of Korea, were included in a retrospective analysis of medical records. Results: Over 14 years, 14 patients (male-to-female ratio of 1:1) were diagnosed with B. cepacia UTI. Of 14 patients with UTI, 11 patients were admitted to the intensive care unit, and a bladder catheter was present in 9 patients when urine culture was positive for B. cepacia. Patients had multiple predisposing factors for UTI, including double-J catheter insertion (14.2%), vesico-ureteral reflux (28.6%), congenital heart disease (28.6%), or malignancy (21.4%). Burkholderia cepacia isolates were sensitive to piperacillin-tazobactam and sulfamethoxazole-trimethoprim, and resistant to amikacin and colistin. Treatment with parenteral or oral antimicrobial agents including piperacillin-tazobactam, ceftazidime, meropenem, and sulfamethoxazole-trimethoprim resulted in complete recovery from UTI. Conclusion: Burkholderia cepacia may be a causative pathogen for nosocomial UTI in pediatric patients with predisposing factors, and appropriate selection of antimicrobial therapy is necessary because of high levels of resistance to empirical therapy, including aminoglycosides.