[Intestinal microbe Prevotella in pulmonary tuberculosis research].

Tuberculosis is a major global infectious disease that seriously endangers human health. Studies have shown that there will be an imbalance of intestinal microecology after infection with Mycobacterium tuberculosis. And vise versa the imbalance of intestinal flora will also increase the susceptibility to Mycobacterium tuberculosis. Prevotella is a newly discovered intestinal microorganism closely related to inflammatory diseases, and its abundance changes significantly in patients with tuberculosis. Therefore, this paper reviews the correlation between intestinal microorganism Prevotella and pulmonary tuberculosis, in order to provide new ideas for the diagnosis and treatment of pulmonary tuberculosis.

Intention to seek professional help for depression and its associated factors among elderly patients in Tenkera Health Clinic, Melaka, Malaysia.

BACKGROUND: Prevalence of mental disorders such as depression in the elderly is rising with the ageing population. This study is aimed to determine the prevalence of depression, their intention to seek help and the factors associated to seek professional help among elderly patients in a primary care clinic. METHODS: This was a cross-sectional with systematic sampling conducted from June to December 2019 in Tengkera Health Clinic (THC). Patient Health Questionnaire- 9 (PHQ-9), socioeconomic data and a dichotomous yes-no response for intention to seek help was collected from 273 elderly patients attending the outpatient clinic. RESULTS: The prevalence of elderly depression at THC was 10.3% and the prevalence of intention to seek professional help for depression among elderly patients at Tengkera Health Clinic was 27.5%. Factors that were associated with intention to seek professional help for depression were prior experience of seeking professional help, adjusted OR 3.45[95%CI (1.41-8.48)] and education level of the respondents- secondary education, adjusted OR 3.10 [95%CI (1.01-9.53)] comparing with no formal education; tertiary education, adjusted OR 4.66 [95%CI (1.08-20.04)] comparing with no formal education. CONCLUSION: The prevalence of elderly depression was high while the prevalence of intention to seek professional help for depression in the sample population was low. Primary care physicians play a vital role in identifying elderly patients with low education level for screening and treatment as well as promoting awareness and breaking down barriers and stigma towards mental illness.

How does Pseudomonas aeruginosa affect the progression of bronchiectasis?

BACKGROUND: Pseudomonas aeruginosa is one of the most common pathogens isolated from respiratory tract specimen in patients with bronchiectasis. It is considered highly responsible for pathogenicity, progression and clinical outcomes of bronchiectasis. AIMS: To summarize existing evidence on how different factors of Pseudomonas aeruginosa affect the pathogenicity, progression and clinical outcomes of bronchiectasis, so as to provide possible insights for clinical practice and related research in the future. SOURCES: PubMed was searched for studies pertaining to bronchiectasis and P. aeruginosa published to date, with no specific inclusion or exclusion criteria. Reference lists of retrieved reviews were searched for additional articles. CONTENT: This review focused on non-cystic fibrosis bronchiectasis and also provided some data on cystic fibrosis when studies in bronchiectasis were limited. We discussed various factors in relation to P. aeruginosa: virulence factors, drug resistance, regulatory systems, genomic diversity and transmission of P. aeruginosa, as well as treatment for P. aeruginosa. Their impacts on bronchiectasis and its management were discussed. IMPLICATIONS: The impact of P. aeruginosa on bronchiectasis is definite, although conclusions in some aspects are still vague. Faced with the worrying drug-resistance status and treatment bottleneck, individualized management and novel therapies beyond the classic pathway are most likely to be a future trend. To confirm the independent or integrated impact of various factors of P. aeruginosa on bronchiectasis and to figure out all the problems mentioned, larger randomized control trials are truly needed in the future.

A prospective evaluation of minimal residual disease as risk stratification for CCLG-ALL-2008 treatment protocol in pediatric B precursor acute lymphoblastic leukemia.

OBJECTIVE: The aim of this prospective study was to evaluate the cut-off value of minimal residual disease (MRD) in predicting the efficacy of CCLG-ALL-2008 or CCLG-2008 treatment protocol on pediatric B-precursor ALL (BP-ALL). PATIENTS AND METHODS: Three hundred and seventy-nine Chinese pediatric BP-ALL were enrolled in this study between Dec 2008 and Sep 2013 in two stratified cohorts. One hundred and fifty-three patients enrolled between Dec 2008 and Oct 2010 as the first cohort, and 196 patients enrolled from Nov 2010 to Sep 2013 as the second cohort. Clinical and biological characteristics and 5 years EFS, RFS, and OS were analyzed. RESULTS: Patients with E2A-PBX1 showed a favorable treatment response with a lower minimal residual disease (MRD) level (< 10-4) at the time point 1 (TP1, p = 0.039) and the highest proportion of the 5-year EFS, RFS, and OS. A high level of MRD was associated with high WBC counts, increased age, BCR-ABL1 fusion gene, MLL rearrangements and adverse karyotypes. In comparison with the first cohort, the second cohort with the MRD assay incorporated prospectively, the standard risk (SR) and the intermediate risk (IR) patients showed a better RFS, EFS, and OS while the high-risk (HR) patients displayed worse RFS, EFS, and OS than those of the first cohort, respectively. Patients with MRD level at either 10-4 or 10-3 showed a similar OS at TP1 or TP2, and patients with MRD level above 10-2 had the worst OS. CONCLUSIONS: This study indicated that the levels of MRD to be an adequate guide in risk-adapted treatment under the CCLG-ALL-2008 protocol and can be adapted to the future development of advanced clinical protocols.

Activation of NRG1-ERBB4 signaling potentiates mesenchymal stem cell-mediated myocardial repairs following myocardial infarction.

Mesenchymal stem cell (MSC) transplantation has achieved only modest success in the treatment of ischemic heart disease owing to poor cell viability in the diseased microenvironment. Activation of the NRG1 (neuregulin1)-ERBB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) signaling pathway has been shown to stimulate mature cardiomyocyte cell cycle re-entry and cell division. In this connection, we aimed to determine whether overexpression of ERBB4 in MSCs can enhance their cardio-protective effects following myocardial infarction. NRG1, MSCs or MSC-ERBB4 (MSC with ERBB4 overexpression), were transplanted into mice following myocardial infarction. Superior to that of MSCs and solely NRG1, MSC-ERBB4 transplantation significantly preserved heart functions accompanied with reduced infarct size, enhanced cardiomyocyte division and less apoptosis during early phase of infarction. The transduction of ERBB4 into MSCs indeed increased cell mobility and apoptotic resistance under hypoxic and glucose-deprived conditions via a PI3K/Akt signaling pathway in the presence of NRG1. Unexpectedly, introduction of ERBB4 into MSC in turn potentiates NRG1 synthesis and secretion, thus forming a novel NRG1-ERBB4-NRG1 autocrine loop. Conditioned medium of MSC-ERBB4 containing elevated NRG1, promoted cardiomyocyte growth and division, whereas neutralization of NRG1 blunted this proliferation. These findings collectively suggest that ERBB4 overexpression potentiates MSC survival in the infarcted heart, enhances NRG1 generation to restore declining NRG1 in the infarcted region and stimulates cardiomyocyte division. ERBB4 has an important role in MSC-mediated myocardial repairs.

Rap1-mediated nuclear factor-kappaB (NF-κB) activity regulates the paracrine capacity of mesenchymal stem cells in heart repair following infarction.

Paracrine effect is the major mechanism that underlies mesenchymal stem cells (MSC)-based therapy. This study aimed to examine how Rap1, telomeric repeat-binding factor 2-interacting protein 1 (Terf2IP), which is a novel modulator involved in the nuclear factor-kappaB (NF-κB) pathway, regulates the paracrine effects of MSC-mediated heart repair following infarction. NF-κB activity of stromal cells was increased by Rap1 as measured by pNF-κB-luciferase reporter activity, and this was abolished by IkB-dominant-negative protein. Knockdown of Rap1 with shRap1 resulted in diminished translocation of p65-NF-κB from the cytoplasm to nuclei in response to tumor necrosis factor-α (TNF-α) stimulation. Compared with BM-MSCs, Rap1(-/-)-BM-MSCs displayed a significantly reduced ratio of phosphorylated NF-κB to NF-κB-p65 and of Bax to Bcl-2, and increased resistance to hypoxia-induced apoptosis by the terminal deoxynucleotidal transferase-mediated dUTP nick end labeling (TUNEL) assay. In contrast, re-expression of Rap1 in Rap1(-/-)-BM-MSCs resulted in loss of resistance to apoptosis in the presence of hypoxia. Moreover, absence of Rap1 in BM-MSCs led to downregulation of NF-κB activity accompanied by reduced pro-inflammatory paracrine cytokines TNF-α, IL (interleukin)-6 and monocyte chemotactic protein-1 in Rap1(-/-)-BM-MSCs compared with BM-MSCs. The apoptosis of neonatal cardiomyocytes (NCMCs) induced by hypoxia was significantly reduced when cocultured with Rap1(-/-)-BM-MSC hypoxic-conditioned medium (CdM). The increased cardioprotective effects of Rap1(-/-)-BM-MSCs were reduced when Rap1(-/-)-BM-MSCs were reconstituted with Rap1 re-expression. Furthermore, in vivo study showed that transplantation of Rap1(-/-)-BM-MSCs significantly improved heart function, decreased infarct size, prevented cardiomyocyte apoptosis and inhibited inflammation compared with controls and BM-MSCs (P<0.01). This study reveals that Rap1 has a critical role in the regulation of MSC paracrine actions. Compared with BM-MSCs, Rap1(-/-)-BM-MSCs decreased NF-κB sensitivity to stress-induced pro-inflammatory cytokine production and reduced apoptosis. Selective inhibition of Rap1 in BM-MSCs may be a novel strategy to enhance MSC-based therapeutic efficacy in myocardial infarction.

Inhibition of rat neuronal kainate receptors by cis-unsaturated fatty acids.

1. Whole-cell recordings from cultured rat hippocampal neurons, from freshly dissociated dorsal root ganglion (DRG) neurons and from human embryonic kidney (HEK) 293 cells expressing the glutamate receptor GluR6 subunit were used to study the modulation of kainate receptor channels by long chain fatty acids. 2. In all three cell types, application of cis-unsaturated fatty acids caused a dose-dependent reduction in whole-cell currents evoked by kainate. Docosahexaenoic acid (DHA), arachidonic acid (AA), linolenic acid and linoleic acid all produced substantial inhibition at a concentration of 50 microM, whereas inhibition by linolenelaidic acid and linolelaidic acid was significantly weaker. Fully saturated fatty acids were essentially inactive. 3. With continuous exposure to active fatty acids, the peak current elicited by kainate declined over a time course of several minutes to reach a steady-state level less than 50 % of the initial amplitude. Recovery was slow in control solution, but was speeded up by exposure to bovine serum albumin (0.5 mg ml-1), a protein that binds fatty acids with submicromolar affinity. The inhibition in neurons was half-maximal with 5-15 microM AA or DHA, but potency was at least 10-fold greater at GluR6 in HEK 293 cells. 4. Inhibition by AA or DHA was unaffected by extracellular nordihydroguaiaretic acid (10 microM), indomethacin (10 microM), 17-octadecynoic acid (30 microM) or 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine dihydrochloride (H-7; 10 microM). Furthermore, inclusion of H-7 (100 microM), BAPTA (10 mM), AA (50 microM), antioxidants, or the protein kinase C inhibitor PKC19-36 (20 microM) in the internal solution had little effect on whole-cell currents and did not prevent inhibition of currents by extracellular application of AA or DHA. 5. We conclude that the inhibition produced by cis-unsaturated fatty acids does not require conversion to oxidized metabolites or activation of PKC. Instead, active compounds may interact directly with an extracellular, or intramembraneous, site on kainate receptors.