Asprosin attenuates insulin signaling pathway through PKCδ-activated ER stress and inflammation in skeletal muscle.

It has been reported that asprosin is a novel adipokine which is augmented in mice and humans with type 2 diabetes (T2DM). Asprosin stimulates hepatic gluconeogenesis under fasting conditions. However, the roles of asprosin in inflammation, endoplasmic reticulum (ER) stress, and insulin resistance in skeletal muscle has not been studied. In the currents study, elevated levels of asprosin expression were observed in adipocytes under hyperlipidemic conditions. Treatment of C2C12 myocytes with asprosin-induced ER stress markers (phosphorylated inositol-requiring enzyme 1 and eukaryotic initiation factor 2, and CHOP expression) as well as inflammation markers (interleukin-6 expression, phosphorylated IκB, and nuclear translocated nuclear factor-κß). Finally, asprosin treatment promoted exacerbation of insulin sensitivity as determined by levels of insulin receptor substrate 1 and Akt phosphorylation as well as glucose uptake. Moreover, treatment of asprosin augmented protein kinase C-δ (PKCδ) phosphorylation and nuclear translocation, but suppressed messenger RNA expression of sarcoplasmic reticulum Ca2+ ATPase 2b in both C2C12 myocytes and in mouse soleus skeletal muscle. These asprosin-induced effects were markedly decreased in small interfering (si) RNA-mediated PKCδ-knockdown in C2C12 myocytes. These results suggest that asprosin results in impairment of insulin sensitivity in skeletal muscle through PKCδ-associated ER stress/inflammation pathways and may be a valuable strategy for management of insulin resistance and T2DM.

p-Coumaric acid stimulates longitudinal bone growth through increasing the serum production and expression levels of insulin-like growth factor 1 in rats.

The aim of the present study was to examine the effects of p-coumaric acid on the longitudinal growth of the long bone in adolescent male rats. Teatment with p-coumaric acid significantly increased the tibial length and the height of each growth plate zone and the ratio of 5-bromo-2'-deoxyuridine-positive cells relative to total proliferative cells. Expression of insulin-like growth factor 1 and its receptor in the proliferative and hypertrophic zones, and serum levels of growth hormone and insulin-like growth factor 1 were significantly increased as well in the p-coumaric acid-treated group. Via increasing both the serum level of insulin-like growth factor 1 and its expression, p-coumaric acid could promote cell proliferation in growth plate zones. These results suggest that p-coumaric acid has the potential to increase height and may be a feasible alternative to growth hormone therapy.

Factors affecting rotator cuff integrity after arthroscopic repair for medium-sized or larger cuff tears: a retrospective cohort study.

BACKGROUND: We wished to identify the preoperative prognostic factors associated with structural integrity after repair of medium-sized and larger rotator cuff tears and to determine the cutoff values using receiver operating characteristic curve analysis. METHODS: The study included 180 patients with medium-sized and larger rotator cuff tears. Each had a minimum 2-year postoperative follow-up by magnetic resonance imaging. We assessed several patient-related and disease-related preoperative factors using univariate and multivariate logistic regression analysis. To determine the cutoff value for the significant variables, receiver operating characteristic curve analysis was performed. RESULTS: Retears occurred in 28 of the 180 patients (15.6%). Univariate analysis found that retear was significantly affected by the type of work and pattern of tear. The rate of retear was significantly increased in diabetes and with increasing tear size, extent of retraction, delamination, and fatty infiltration. Furthermore, reduced remnant tendon length, distance from the musculotendinous junction to the face of the glenoid, occupation ratio, and acromiohumeral interval were also significant risk factors. In the multivariate analysis, body mass index, diabetes, dyslipidemia, extent of retraction, delamination, distance from musculotendinous junction to face of glenoid, occupation ratio, fatty infiltration of infraspinatus, and acromiohumeral interval remained significant risk factors. The extent of retraction (22.2 mm) and the occupation ratio (53.5%) showed highly accurate cutoff values for predicting retear. CONCLUSION: Multiple factors influenced the healing process after rotator cuff repair. The best predictors were the extent of retraction and occupation ratio, which could help assist in determining the prognosis after rotator cuff repairs.

Phosphatidylcholine causes adipocyte-specific lipolysis and apoptosis in adipose and muscle tissues.

Phosphatidylcholine (PPC) formula has been therapeutically used to reduce areas of localized fat. However, no single research has been carried out on its effect on a variety of cells in adipose and muscle tissues. Herein, the current study aimed to explore the activity of PPC on different cells in adipose and muscle tissues and to investigate the molecular mechanisms contributing to the effects of PPC on lipolysis and apoptosis. mRNA expression levels of various genes were measured by quantitative real-time PCR. Protein expression levels were observed through Western blotting and cell viability was measured by MTT assay. Lipolysis and caspase 3 activity assay were performed using commercial kits. PPC induces lipolysis and apoptosis in adipocytes (3T3-L1), but not in the other tested cells, including skeletal muscle cells (C2C12 myocytes), endothelial cells (HUVEC), and fibroblasts (BJ). The possible role of TNFα and IL-1ß-mediated pathways on the effects of PPC was also revealed. We confirmed that treatment with PPC caused lipolysis and apoptosis in a dose-dependent manner (only in 3T3-L1 adipocytes). The effect of PPC observed in 3T3-L1 adipocytes was not evident in C2C12 myocytes, HUVEC, and fibroblasts. PPC also increased TNFα and IL-1ß expression and release in 3T3-L1 adipocytes in a dose-dependent fashion, but not in C2C12 myocytes, HUVEC, and BJ. Suppression of TNFα or IL-1ß reversed PPC-induced lipolysis and apoptosis in 3T3-L1 adipocytes, suggesting that PPC could promote adipocyte-specific lipolysis and apoptosis through TNFα and IL-1ß-mediated signaling. We conclude that the specific activity of PPC on adipocyte in adipose without other tissue damages can be an effective approach for melting lipid.

Cytokine responses induced by Mycobacterium tuberculosis in patients with HIV-1 infection and tuberculosis.

OBJECTIVE: Tuberculosis (TB) is an important opportunistic infection in HIV patients. Immune responses to Mycobacterium tuberculosis in HIV/TB patients were evaluated. METHODS: Fifteen patients with HIV/TB, ten with HIV, four with TB, and five controls were enrolled. Peripheral blood mononuclear cells were isolated and stimulated with mycobacterial antigen (PPD). Interferon (IFN)-gamma and TNF-alpha in culture supernatants were measured by ELISA. RESULTS: IFN-gamma and TNF-alpha production after PPD stimulation was markedly decreased in HIV patients, but not in HIV/TB patients. In HIV patients with a CD4 cell count of less than 200/mm3, IFN-gamma and TNF-alpha production after PPD stimulation was higher in HIV/TB patients than in HIV patients. Cytokine responses to M. tuberculosis reconstituted after highly active antiretroviral therapy (HAART) and were prominent in HIV/TB patients. CONCLUSIONS: Cytokine responses to M. tuberculosis were retained in HIV-infected patients with tuberculosis, even in patients with a CD4 cell count of less than 200/mm3, and reconstituted after HAART.

Determination of genetic subtypes of HIV type 1 isolated from Korean AIDS patients.

To determine HIV-1 subtypes in Korean patients, we analyzed the nucleotide sequences of the HIV-1 env gene isolated from 19 Korean patients. DNA was extracted from cultured lymphocytes and the proviral V3 env gene was amplified by nested polymerase chain reaction. DNA sequences were determined using a cycle sequencer with fluorescence-labeled dye terminators, and aligned using a set of reference sequences. The phylogenetic tree was constructed by the neighbor-joining method. Most of the enrolled patients were in the advanced stage of AIDS with CD4+ lymphocyte counts ranging from 10 to 560 (median 50) per mm3. Eighteen of the nineteen patients' sequences fall into subtype B (95%) and one was subtype A (5%). The tetrameric motifs at the tip of the V3 loop were comprised of GPGR (10 cases, 53%), GPGS (5 cases, 26%), and GPGQ, GPGG, GQGR, and APGS (one case each, 5%). Subtype B was found to be the most predominant clade of HIV-1 in our AIDS patients.

Disseminated erythematous papules in a renal transplant recipient: a case of disseminated tuberculosis.

The incidence of tuberculosis in renal transplant patients has been reported to be fairly low and disseminated tuberculosis presenting with cutaneous manifestations has not been reported previously in these patients. We report the case of a 62-y-old kidney transplant recipient with a long-term history of chronic immunosuppressive therapy who presented with high fever, rapidly progressing respiratory failure and disseminated erythematous pustular cutaneous lesions.