Inhibition of Serine Protease Activity Protects Against High Fat Diet-Induced Inflammation and Insulin Resistance.

Recent evidence suggests that enhanced protease-mediated inflammation may promote insulin resistance and result in diabetes. This study tested the hypothesis that serine protease plays a pivotal role in type 2 diabetes, and inhibition of serine protease activity prevents hyperglycemia in diabetic animals by modulating insulin signaling pathway. We conducted a single-center, cross-sectional study with 30 healthy controls and 57 patients with type 2 diabetes to compare plasma protease activities and inflammation marker between groups. Correlations of plasma total and serine protease activities with variables were calculated. In an in-vivo study, LDLR-/- mice were divided into normal chow diet, high-fat diet (HFD), and HFD with selective serine protease inhibition groups to examine the differences of obesity, blood glucose level, insulin resistance and serine protease activity among groups. Compared with controls, diabetic patients had significantly increased plasma total protease, serine protease activities, and also elevated inflammatory cytokines. Plasma serine protease activity was positively correlated with body mass index, hemoglobin A1c, homeostasis model assessment-insulin resistance index (HOMA-IR), tumor necrosis factor-α, and negatively with adiponectin concentration. In the animal study, administration of HFD progressively increased body weight, fasting glucose level, HOMA-IR, and upregulated serine protease activity. Furthermore, in-vivo serine protease inhibition significantly suppressed systemic inflammation, reduced fasting glucose level, and improved insulin resistance, and these effects probably mediated by modulating insulin receptor and cytokine expression in visceral adipose tissue. Our findings support the serine protease may play an important role in type 2 diabetes and suggest a rationale for a therapeutic strategy targeting serine protease for clinical prevention of type 2 diabetes

Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

BACKGROUND: Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. METHODS: We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMA(IR)). The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513. RESULTS: AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMA(IR )≥ 2: 87.2%, and AGT + HOMA(IR )≥ 3.8: 72.3%). None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. CONCLUSION: There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated risk of PCOS amongst Taiwanese subjects. This is quite different from the similar study in phylogenetically diverged Caucasian subjects

Infectious Alopecia in a Dog Breeder After Renal Transplantation

Tinea capitis rarely occurs in renal transplant recipients. We report this living-related renal transplant patient receiving cyclosporine-based therapy who initially presented with severe exfoliation of the scalp with yellowish-white scales and marked hair loss. The lesions extended to the frontal area and both cheeks, resulting in several skin ulcers with perifocal erythematous inflammatory changes, and palpable cervical lymph nodes. A biopsy of a skin lesion revealed fungal infection and culture yielded Microsporum canis. The patient mentioned an outbreak of ringworm in her breeding dogs during this period. After adequate treatment of the patient and her infected animals with griseofulvin and disinfection of the environment, her skin lesions resolved dramatically, with regrowth of hair

Mechanistic Study of the Phytocompound, 2- β

Bidens pilosa, a medicinal herb worldwide, is rich in bioactive polyynes. In this study, by using high resolution 2-dimensional gel electrophoresis coupled with mass spectrometry analysis, as many as 2000 protein spots could be detected and those whose expression was specifically up- or downregulated in Jurkat T cells responsive to the treatment with 2-β-D-glucopyranosyloxy-1-hydroxytrideca-5,7,9,11-tetrayne (GHTT) can be identified. GHTT treatment can upregulate thirteen proteins involved in signal transduction, detoxification, metabolism, energy pathways, and channel transport in Jurkat cells. Nine proteins, that is, thioredoxin-like proteins, BH3 interacting domain death agonist (BID protein involving apoptosis), methylcrotonoyl-CoA carboxylase beta chain, and NADH-ubiquinone oxidoreductase, were downregulated in GHTT-treated Jurkat cells. Further, bioinformatics tool, Ingenuity software, was used to predict signaling pathways based on the data obtained from the differential proteomics approach. Two matched pathways, relevant to mitochondrial dysfunction and apoptosis, in Jurkat cells were inferred from the proteomics data. Biochemical analysis further verified both pathways involving GHTT in Jurkat cells. These findings do not merely prove the feasibility of combining proteomics and bioinformatics methods to identify cellular proteins as key players in response to the phytocompound in Jurkat cells but also establish the pathways of the proteins as the potential therapeutic targets of leukemia

First Total Synthesis of Protoapigenone and Its Analogues as Potent Cytotoxic Agents

Protoapigenone (1), isolated from Thelypteris torresiana, previously showed significant cytotoxic activity against five human cancer cell lines. In a continued structure-activity relationship study, the first total synthesis and modification of 1 were achieved. All synthesized compounds and related intermediates were evaluated for cytotoxic activity against five human cancer cell lines, HepG2, Hep3B, MDA-MB-231, MCF-7 and A549. Among them, 24 showed 2.2-14.2 fold greater cytotoxicity than 1 and naphthyl A-ring analogs remarkably enhanced the activity

In-hospital outcome of patients with culture-confirmed tuberculous pleurisy: clinical impact of pulmonary involvement

<p>Abstract</p> <p>Background</p> <p>Outcomes for hospitalized patients with tuberculous pleurisy (TP) have rarely been reported, and whether or not pulmonary involvement affects outcomes is uncertain. This study aimed to analyze the in-hospital mortality rate of culture-confirmed TP with an emphasis on the clinical impact of pulmonary involvement.</p> <p>Methods</p> <p>Patients who were hospitalized for pleural effusion (PE) of unconfirmed diagnosis and finally diagnosed as TP were identified. We classified them according to the disease extent: isolated pleurisy (isolated pleurisy group) and pleurisy with pulmonary involvement (pleuro-pulmonary group).</p> <p>Results</p> <p>Among the 205 patients hospitalized before the diagnosis was established, 51 (24.9%) belonged to the isolated pleurisy group. Compared to the pleuro-pulmonary group, patients in the isolated pleurisy group were younger, had fewer underlying co-morbidities, and presented more frequently with fever and chest pain. Fewer patients in the isolated pleurisy group had hypoalbuminemia (< 3.5 g/dL) and anemia. The two groups were similar with regards to PE analysis, resistance pattern, and timing of anti-tuberculous treatment. Patients who had a typical pathology of TP on pleural biopsy received anti-tuberculous treatment earlier than those who did not, and were all alive at discharge. The isolated pleurisy group had a lower in-hospital mortality rate, a shorter length of hospital stay and better short-term survival. In addition, the presence of underlying comorbidities and not receiving anti-tuberculous treatment were associated with a higher in-hospital mortality rate.</p> <p>Conclusion</p> <p>In culture-confirmed tuberculous pleurisy, those with pulmonary involvement were associated with a higher in-hospital mortality rate. A typical pathology for TP on pleura biopsy was associated with a better outcome.</p

Nutrient supply in the Southern East China Sea after Typhoon Morakot

Author Posting. © Sears Foundation for Marine Research, 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 133-149, doi:10.1357/002224013807343425.Recent studies show that typhoons have profound effects on phytoplankton assemblages along their tracks, but it is difficult to quantitatively estimate nutrient supply after a typhoon's passage due to a lack of nutrient information before and after the arrival of a typhoon. During the passage of Typhoon Morakot (July 22 to Aug. 26, 2009), we conducted pre- and post-typhoon field cruises to study nutrient supply in the Southern East China Sea (SECS). The results showed nitrate and phosphate supplies to the water column in the SECS after the typhoon's passage were 5.6 × 1011 g-N/day and 7.8 × 1010 g-P/day which were significantly higher than those before the typhoon occurred (nitrate supply = 1 × 109 g-N/day, phosphate supply = 1.6 × 108 g-P/day). We conclude from this data, and after consulting the available physical data, that the highest nitrate concentration was caused by strong upwelling and/or vertical mixing, and input of nutrient-replete terrestrial waters. The nitrate and phosphate input related to the passage of Typhoon Morakot can account for approximately 86% and 87% of summer nitrate and phosphate supplies to the southern East China Sea.This research was supported by the Top University Program and the National Science Council (NSC101-2116M-110- 001, NSC101-2611-M-110-015-MY3, NSC100-2119-M-110-003, NSC98-2611-M-019-014-MY3, NSC NSC98-2611-M-002-019-MY3) of Taiwan to C.-C. Hung, G.-C.Gong and S. Jan

Corrigendum to “Nutrient supply in the Southern East China Sea after Typhoon Morakot”

Author Posting. © Sears Foundation for Marine Research, 2013. This article is posted here by permission of Sears Foundation for Marine Research for personal use, not for redistribution. The definitive version was published in Journal of Marine Research 71 (2013): 451-452, doi:10.1357/002224013812587609