• Journal of Applied Biological Chemistry
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• v.59 no.4
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• pp.289-298
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• 2016

FK506 hyper-yielding mutant, called the TCM8594 strain, was made from Streptomyces tsukubaensis NRRL 18488 by mutagenesis using N-methyl-N'-nitro-N-nitrosoguanidine, ultraviolet irradiation, and FK506 sequential resistance selection. FK506 production by the TCM8594 strain improved 45.1-fold ($505.4{\mu}g/mL$) compared to that of S. tsukubaensis NRRL 18488 ($11.2{\mu}g/mL$). Among the five substrates, wheat bran was selected as the best solid substrate to produce optimum quantities of FK506 ($382.7{\mu}g/g$ substrate) under solid-state fermentation, and the process parameters affecting FK506 production were optimized. Maximum FK506 yield ($897.4{\mu}g/g$ substrate) was achieved by optimizing process parameters, such as wheat bran with 5 % (w/w) dextrin and yeast extract as additional nutrients, 70 % (v/w) initial solid substrate moisture content, initial medium pH of 7.2, $30^{\circ}C$ incubation temperature, inoculum level that was 10 % (v/w) of the cell mass equivalent, and a 10 day incubation. The results showed an overall 234 % increase in FK506 production after optimizing the process parameters.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.257-263
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• 2013

Although pathogenesis of human rheumatoid arthritis (RA) remains unclear, arthritogenic T cells and downstream signaling mediators have been shown to play critical roles. An increasing numbers of therapeutic options have been added for the effective control of RA. Nevertheless, there is still a category of patients that fails treatment and suffers from progressive disease. The recently developed immunosuppressant CP-690550, a small molecule JAK kinase inhibitor, has been implicated as an important candidate treatment modality for autoimmune arthritis. In this study, we evaluated the therapeutic effect of CP-690550 on established arthritis using an SKG arthritis model, a pathophysiologically relevant animal model for human RA. CP-690550 treatment revealed remarkable long-term suppressive effects on SKG arthritis when administered to the well-advanced disease (clinical score 3.5~4.0). The treatment effect lasted at least 3 more weeks after cessation of drug infusion, and suppression of disease was correlated with the reduced pro-inflammatory cytokines, including IL-17, IFN-${\gamma}$, and IL-6 and increased level of immunoregulatory IL-10.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.480-484
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• 2008

The incidence of aspergillosis infections in the maxillary sinus has increased recently, because of overuse of antibiotics, steroids, anticancer agents, immunosuppressant, antimetabollites, and uncontrolled diabetes mellitus. The clinical features of maxillary sinus aspergillosis include pain, swelling and foul odor nasal excretion. This needs to be differentiated from bacterial maxillary sinusitis, and surgical treatment with antifungal agents are suggested. Recently, we treated two patients with maxillary sinus aspergillosis surgically (Caldwell Luc operation) and with antifungal agents(itraconazole). The results were satisfactory so we report these cases with literature review.

• Tuberculosis and Respiratory Diseases
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• v.84 no.1
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• pp.22-34
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• 2021

The coronavirus pandemic, known as coronavirus disease 2019 (COVID-19), is an infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus first identified in patients from Wuhan, China. Since December 2019, SARS-CoV-2 has spread swiftly around the world, infected more than 25 million people, and caused more than 800,000 deaths in 188 countries. Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) appear to be risk factors for COVID-19, however, their prevalence remains controversial. In fact, studies in China reported lower rates of chronic respiratory conditions in patients with COVID-19 than in the general population, while the trend is reversed in the United States and Europe. Although the underlying molecular mechanisms of a possible interaction between COVID-19 and chronic respiratory diseases remain unknown, some observations can help to elucidate them. Indeed, physiological changes, immune response, or medications used against SARS-CoV-2 may have a greater impact on patients with chronic respiratory conditions already debilitated by chronic inflammation, dyspnea, and the use of immunosuppressant drugs like corticosteroids. In this review, we discuss importance and the impact of COVID-19 on asthma and COPD patients, the possible available treatments, and patient management during the pandemic.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.711-721
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• 2022

The immune system is one of the most important parts of the human body and immunomodulation is the major function of the immune system. In response to outside pathogens or high inflammation, the immune system is stimulated or suppressed. Thus, identifying effective and potent immunostimulants or immunosuppressants is critical. Ginsenosides are a type of steroid saponin derived from ginseng. Most are harmless to the body and even have tonic effects. In this review, we mainly focus on the immunostimulatory and immunosuppressive roles of two types ginsenosides: the protopanaxadiol (PPD)-type and protopanaxatriol (PPT)-type. PPT-type ginsenosides include Rg1, Rg2, Rh4, Re and notoginsenoside R1, and PPD-type ginsenosides include Rg3, Rh2, Rb1, Rb2, Rc, Rd, compound K (CK) and PPD, which activate the immune responses. In addition, Rg1 and Rg6 belong to PPT-type ginsenosides and together with Rg3, Rb1, Rd, CK show immunosuppressive properties. Current explorations of ginsenosides in immunological areas are in the preliminary stages. Therefore, this review may provide some novel ideas to researchers who study the immunoregulatory roles of ginsenosides.

• CELLMED
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• v.12 no.3
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• pp.14.1-14.2
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• 2022

Currently, a 70-year-old woman started suffering from S.I joint pain from 1973 and had severe pain in the S.I joint, wrist, and elbow from 1975 to 1977, and was diagnosed with spinal tuberculosis at a general hospital. From 1978 to 1987, she suffered from chronic fatigue and insomnia, and since January 1, 1988, she was unable to get up while lying down, suffering from whole body joint, muscle pain, and fibromyalgia. In May 1989, she was also diagnosed with ankylosing spondylitis through genetic testing at the Catholic St. Mary's Hospital Rheumatology Department in Korea, and was treated with sulfasalazine, analgesic, and immunosuppressant, methotrexate, for 12 years until 1999, but none of the drugs eliminated the pain. She was hospitalized and discharged repeatedly, and continued to receive salt water poultice and exercise therapy at home, but was unable to move at all. In 2000, after biologic treatment with Remicade injection (Remsima®), she was able to walk and move, and after that, she was continuously prescribed biologics. From 2015 to 2019, Enbrel® (Etanercept) injection was prescribed once a week, but the symptoms such as severe pain (joint and muscle, fibromyalgia), scleroderma, Sjogren's syndrome (dryness of eyes, nose and mouth), difficulty swallowing, chronic fatigue, and stiff body appeared. Around January 2018, hepatic indicators were high and lymphocytes became enlarged. However, most serious injuries were highly improved after the OCNT combination therapy using active phytonutrients, anthocyanin-fucoidan nanocomplex. Therefore, for patients with such experiences, OCNT treatment is proposed as an alternative.

• Journal of Marine Bioscience and Biotechnology
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• v.14 no.1
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• pp.33-42
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• 2022

Tacrolimus, a type of macrolide produced by Streptomyces tsukubaensis, is widely used as an immunosuppressant. However, continuous exposure to tacrolimus causes oxidative stress in normal cells, ultimately inducing cell injury. Therefore, this study investigated whether luthione, a reduced glutathione, could inhibit tacrolimus-induced cytotoxicity in olive flounder (hirame) natural embryo (HINAE) cells. According to the results, luthione significantly inhibited tacrolimus-induced reduction in cell viability in a concentration-dependent manner. Additinally, although luthione unaffected autophagy by tacrolimus, tacrolimus-induced apoptosis was significantly suppressed in the presence of luthione. Luthione also markedly blocked DNA damage in tacrolimus-treated HINAE cells, associated with the inhibition of reactive oxygen species (ROS) generation. Additionally, tacrolimus cytotoxicity in HINAE cells was correlated with increased inflammatory response, also attenuated by luthione. Collectively, these results show that at least luthione protects HINAE cells against tacrolimus-induced DNA damage, apoptosis, and inflammation, but not autophagy, by scavenging ROS. Although additional in-vivo studies are required, this study's results can be used as a basis for utilizing luthione to reduce the toxicity of fish cells caused by excessive immune responses.

• Journal of Veterinary Science
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• v.24 no.5
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• pp.66.1-66.7
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• 2023

Two dogs presented with bilateral pattern-forming corneal opacity. Treatment with topical immunosuppressants was initiated after a complete ophthalmic examination. The response to treatment was assessed by analyzing serial images using slit-lamp biomicroscopy and spectral domain optical coherence tomography (SD-OCT). Both dogs responded to topical immunosuppressants; however, the lesions recurred once the treatment was abated or withdrawn. The most effective immunosuppressant in both dogs was 0.03% tacrolimus ointment. Early and continuous treatment with topical immunosuppressants may be necessary to improve corneal clarity and prevent scarring. SD-OCT could provide useful structural information regarding presumed immune-mediated keratitis and aid in monitoring treatment response.

• Childhood Kidney Diseases
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• v.28 no.1
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• pp.44-50
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• 2024

Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease that affects multiple organs. More than half of the patients with SLE have kidney involvement, and up to 10% of patients with lupus nephritis develop end-stage renal disease (ESRD). Central nervous system (CNS) involvement in SLE occurs in 21% to 95% of patients. Severe neurological manifestations such as seizures, cerebrovascular disease, meningitis, and cerebrovascular accidents can develop in childhood-onset SLE, but cerebral infections, such as brain abscess and hemorrhage, are seldom reported in lupus nephritis, even in adults. Here, we report a rare case of childhood-onset SLE with ESRD, cerebral abscess, and hemorrhage. A 9-year-old girl diagnosed with lupus nephritis was administered high-dose steroids and immunosuppressant therapy to treat acute kidney injury (AKI) and massive proteinuria. The AKI deteriorated, and after 3 months, she developed ESRD. She received hemodialysis three times a week along with daily peritoneal dialysis to control edema. She developed seizures, and imaging showed a brain abscess. This was complicated by spontaneous cerebral hemorrhage, and she became unstable. She died shortly after the hemorrhage was discovered. In conclusion, CNS complications should always be considered in clinical practice because they increase mortality, especially in those with risk factors for infection.

• Korean Journal of Veterinary Service
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• v.47 no.2
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• pp.89-94
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• 2024

A 5-year-old spayed female mixed-breed dog, previously receiving 7 months of immunosuppressive therapy for pemphigus foliaceus, presented to our referral hospital with a history of dog bites on the right forelimb, chest, and flank 4 days prior to presentation. Physical examination revealed a rectal temperature of 38.6℃; heart rate of 130 beats per minute; panting; systolic blood pressure of 60 mmHg; and swelling, purulent discharge, warmth, pain, and lameness in the right forelimb. The laboratory investigation revealed neutropenia and elevated C-reactive protein levels. Suppurative neutrophilic infiltration with bacterial infection was detected by impression cytology of the pus on the right forelimb. Based on the results of the clinical examinations and laboratory tests, the dog was diagnosed with dog bite-induced sepsis with pemphigus. Meropenem and metronidazole were prescribed. Clinical signs, neutropenia, and C-reactive protein levels markedly improved after 5 days. Subsequently, pemphigus foliaceus relapsed in the dog, and it is currently undergoing re-administration of immunosuppressive medications. To the best of our knowledge, this is the first case report of successful management of dog bite-induced sepsis in a dog undergoing long-term immunosuppressive therapy.