Coexistence of anti-MDA5 and anti-PL-7 in a patient with dermatomyositis: A case report.

Coexisting anti-MDA5 and anti-PL-7 antibodies are extremely rare. Anti-MDA5 is associated with rapidly progressive interstitial lung disease (RP-ILD), while anti-PL-7 is often associated with chronic or subacute ILD and better outcomes than RP-ILD. We report a 41-year-old woman diagnosed with dermatomyositis (DM)-associated ILD positive for anti-MDA5 and anti-PL-7.

Reduced frequencies of Foxp3+GARP+ regulatory T cells in COPD patients are associated with multi-organ loss of tissue phenotype.

BACKGROUND: Expression of glycoprotein A dominant repeat (GARP) has been reported to occur only in activated human naturally occurring regulatory T cells (Tregs) and their clones, and not in activated effector T cells, indicating that GARP is a marker for bona fide Tregs. A different phenotype of chronic obstructive pulmonary disease (COPD) may have a different immunologic mechanism. OBJECTIVE: To investigate whether the distribution of Tregs defined by GARP is related to the multi-organ loss of tissue phenotype in COPD. METHODS: GARP expression on T cells from peripheral blood and bronchoalveolar lavage (BAL) collected from patients with COPD was examined by flow cytometry. The correlation of GARP expression to clinical outcomes and clinical phenotype, including the body mass index, lung function and quantitative computed tomography (CT) scoring of emphysema, was analyzed. RESULTS: Patients with more baseline emphysema had lower forced expiratory volume, body mass index (BMI), worse functional capacity, and more osteoporosis, thus, resembling the multiple organ loss of tissue (MOLT) phenotype. Peripheral Foxp3+GARP+ Tregs are reduced in COPD patients, and this reduction reversely correlates with quartiles of CT emphysema severity in COPD. Meanwhile, the frequencies of Foxp3+GARP- Tregs, which are characteristic of pro-inflammatory cytokine production, are significantly increased in COPD patients, and correlated with increasing quartiles of CT emphysema severity in COPD. Tregs in BAL show a similar pattern of variation in peripheral blood. CONCLUSION: Decreased GARP expression reflects more advanced disease in MOLT phenotype of COPD. Our results have potential implications for better understanding of the immunological nature of COPD and the pathogenic events leading to lung damage.

Research on Radiosensitivity of the Protein Kinase B Signaling Pathway in Cervical Cancer.

The main characteristics of cervical cancer are abnormal and uncontrolled cell proliferation, and it regulates cell growth, differentiation, and cell death through genetic and epigenetic changes. This paper mainly discusses the radiosensitivity of the cervical cancer protein kinase B signaling pathway and discusses the specific mechanisms that affect the occurrence and development of cervical cancer. In addition, this paper studies the effect of transient transfection knocking down the expression of TRIP4 in cervical cancer cells on the expression of key proteins in related signaling pathways and explores the mechanism of its specific effects and finds the mechanism of TRIP4's effect on cervical cancer radiosensitivity. The findings of this study show for the first time that knocking down TRIP4 inhibits cell viability by inhibiting the P13K/AKT and MAPK/ERK pathways, and this corresponds to the first part of the experimental results, which show that knocking down TRIP4 inhibits colony formation and increases apoptosis in HeLa and SiHa cells. Moreover, simultaneous inhibition of TRIP4 and hTERT proteins can increase the radiosensitivity of cervical cancer cells. These findings indicate that the inhibition of TRIP4 may be a new type of treatment that selectively targets the P13K/AKT and MAPK/ERK pathways and hTERT pathways in cervical cancer cells and provides a therapeutic option for the treatment of cervical cancer.

[The Effect and Mechanism of Hyperin on Ovarian Reserve of Tripterygium Glycosides-Induced POI Mice].

OBJECTIVE: To investigate the effect and mechanism of hyperin on the improvement of ovarian reserve of tripterygium glycosides (TG)-induced primary ovarian insufficiency (POI) in mice. METHODS: Adult female BALB/c mice were used as research subjects and were randomly assigned to the control group, POI model group and hyperin treatment group, with 40 mice in each group. TG was given at 40 mg/kg twice a day by gavage for 2 weeks to create the POI mouse model. Mice in the hyperin treatment group were given hyperin at 75 mg/(kg·d) by gavage for 4 weeks after the model was established. The body mass of the mice was weighed and the gonadal index was calculated. Ovarian histological changes were observed by HE staining, and the number of follicles at all levels was calculated. Serum estradiol (E 2), follicle-stimulating hormone (FSH), anti-mullerian hormone (AMH), superoxide dismutase (SOD) and catalase (CAT) were assessed with ELISA. The mRNA and protein levels of nuclear factor (erythroid-derived 2)-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1), Caspase3, Bcl-2 and Bax in ovarian granulosa cells were measured by RT-qPCR and Western blot. The protein levels of phosphorylated phosphatidylinositol 3-hydroxy kinase (p-PI3K) and phosphorylated protein kinase B (p-Akt) were measured by Western blot. The reactive oxygen species (ROS) levels in granulosa cells were determined by H2DCFDA. The apoptosis of granulosa cells was examined by TUNEL assay. RESULTS: Compared with mice in the POI model group, the body mass and gonadal index of hyperin-treated mice increased (all P<0.05). The pathological damage of the ovary decreased, and the number of follicles at all levels and corpora lutea increased (all P<0.05). Serum E 2, AMH, SOD and CAT levels increased, and FSH level decreased (all P<0.05). At the molecular level, the expression of Nrf-2, HO-1, p-PI3K, p-Akt and Bcl-2 in ovarian granulosa cells increased, while the expression of Caspase3 and Bax decreased (all P<0.05). ROS level decreased ( P<0.05). TUNEL assay showed reduced apoptosis of granulosa cells ( P<0.05). CONCLUSION: Hyperin improved ovarian reserve in TG-induced POI mice through Nrf-2/HO-1antioxidant stress response and the anti-apoptotic effect of PI3K/Akt pathways.

Transcription factor PyHY5 binds to the promoters of PyWD40 and PyMYB10 and regulates its expression in red pear 'Yunhongli No. 1'.

'Yunhongli No. 1' is a rare and well-colored red pear (Pyrus pyrifolia) germplasm resource, and is popular in the market due to its bright red color and high quality. Light induces the expression of transportation factor genes MYB10, WD40, and HY5, which then activate the expression of critical genes in the anthocyanin biosynthesis pathway to promote the synthesis and accumulation of anthocyanin, thus giving the red coloration. Protein HY5 is considered to be a key regulator for induction of anthocyanin biosynthesis. The MYB10 genes physically interact with HY5 to positively regulate anthocyanin biosynthesis in Arabidopsis, apple, and pear by binding to G-box motifs. However, how these transcription factors are regulated by sunlight remains unclear in 'Yunhongli No. 1'. In this study, the transcription factor PyHY5 was cloned, and subcellular localization assay showed that PyHY5 was distributed in the nucleus. The DNA fragments of PyHY5 had a typical BRLZ domain of the bZIP family, and then were aligned against the promoter sequences of PyMYB10 and PyWD40. Electrophoretic mobility shift and transient expression assays showed that PyHY5 could directly recognize and bind to the G-box motifs in the promoters of PyMYB10 and PyWD40, and so boosted transcriptional activation by co-expression. The results demonstrated that PyHY5 binding to G-box motifs of the promoters of PyMYB10 and PyWD40, enhanced its expression, and then promoted accumulation of anthocyanin in red 'Yunhongli No. 1'.

Complete regression of pulmonary squamous carcinoma in IPF following gemcitabine plus cisplatin: a case report and literature review.

BACKGROUND: Lung cancer is one of the most common co-morbid conditions in patients with idiopathic pulmonary fibrosis (IPF) and negatively affects the prognosis of IPF; Current guidelines for the management of IPF do not give a clear statement on how to manage these patients, and traditional chemotherapy for lung cancer had a limited efficiency rate. Here, we present a rare case of primary lung squamous carcinoma in a patient with IPF whose tumor completely regressed following gemcitabine plus cisplatin therapy; the cancer was no longer detectable after 2 years upon follow-up. CASE PRESENTATION: Sixty-seven year-old male patient with IPF was admitted to hospital due to acute onset hemoptysis. In addition to a definite usual interstitial pneumonia (UIP) pattern, a chest CT scan showed a non-enhancing nodular opacity in the right upper lobe and an enhancing nodule in the right lower lobe. Bronchoscopic biopsy of the nodule in the right lower lobe revealed squamous lung cancer. After 2 cycles of chemotherapy with gemcitabine and cisplatin, the tumor in the right lower lobe was no longer detectable after 2 years of follow-up; however, the nodule in the right upper lobe had increased significantly. Finally, Mycobacterium tuberculosis (MTB) was cultured from the bronchoalveolar (BAL) sample submitted at the last evaluation, and the patient was confirmed to have active pulmonary TB. CONCLUSION: We report the first documented case of complete pulmonary squamous carcinoma regression in IPF following gemcitabine plus cisplatin. Traditional chemotherapy is considered inadequate to cause the resulting regression of the tumor. The concomitant active pulmonary tuberculosis possibly underlies the mechanism.

Characterization of the complete chloroplast genome of Pyrus pyrifolia 'Yunhongli No. 1'.

'Yunhongli No. 1' is a rare and well-colored red pear (Pyrus pyrifolia) germplasm resource, and is popular in the market due to its bright red color and high quality. This study used Illumina high-throughput sequencing technologies for red pear 'Yunhongli No. 1' of chloroplast genome sequencing and analysis. The genome features of P. pyrifolia 'Yunhongli No. 1' and the phylogenetic relationships were reported and established. The complete chloroplast genome is 160,113 bp in length, consisting of a pair of inverse duplication regions 26,386 bp, a large single-copy region 88,052 bp, and a small single-copy region 19,214 bp. The entire genome contains 80 messenger RNA (mRNA) genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The phylogenetic tree of 15 Rosaceae species revealed red pear 'Yunhongli No. 1' is more closely related to Pyrus communis × P. pyrifolia 'Greensis.'

Increased pro-inflammatory cytokine-secreting regulatory T cells are correlated with the plasticity of T helper cell differentiation and reflect disease status in asthma.

BACKGROUND: Human regulatory T cells (Tregs) are a heterogeneous population which consists of three distinct subpopulations: CD25+CD45RA+ resting Treg (rTreg) cells; CD25hiCD45RA- activated Treg (aTreg) cells, which are both suppressive; and CD25+CD45RA- cytokine-secreting T cells with pro-inflammatory capacity. OBJECTIVE: We investigated variation in peripheral Treg subpopulations of asthma and explored their potential roles in asthma inflammation. METHODS: Twenty-eight mild asthma patients, 26 moderate asthma patients, 18 severe asthma patients, and 36 healthy controls were recruited for a cross-sectional study. Phenotyping of peripheral CD4+ Tregs was performed based on flow cytometry results. RESULTS: The proportions of rTreg and aTreg cells among CD4+ T cells were higher in mild and moderate asthma patients than in healthy controls. All three groups of asthmatics had a higher proportion of pro-inflammatory Tregs than healthy controls, and these increased with asthma severity. The proportion of IL-17-producing Foxp3+ cells and IFN-ɤ-producing Foxp3+ cells strongly correlated with T helper 17 (Th17) cells (r = 0.66, p < 0.001) and Th1 cells (r = 0.48, p < 0.001). The pro-inflammatory Treg subpopulation was correlated with the severity of asthma and may be insensitive to corticosteroids. CONCLUSIONS: Our data suggest that pro-inflammatory Treg subpopulations may be relevant to the plasticity of Th17 and Th1 differentiation and play an important role in the pathogenesis of asthma.