Effects of magnanimous therapy on emotional, psychosomatic and immune functions of lung cancer patients

This study was a randomised controlled study on the effects of the individual computer magnanimous therapy and group computer magnanimous therapy on emotional, psychosomatic and immune function among advanced lung cancer patients. Patients were examined at baseline and 2 weeks later using the Psychosomatic Status Scale for Cancer Patients, Hospital Anxiety Depression Scale and IgA, IgG, IgM and natural killer cell functions. The results showed that individual computer magnanimous therapy and group computer magnanimous therapy were beneficial for advanced lung cancer patients in improving depression, anxiety, psychosomatic status and immune functions. The improvements of immune functions may be related to the improvements of the participants’ emotional and psychosocial status

Nurse-led cognitive screening model for older adults in primary care

Author version made available in accordance with publisher copyright. Under 12 month embargo from date of publication [26 September 2014]. This is the accepted version of the following article: [Yang, Y., Xiao, L. D., Deng, L., Wang, Y., Li, M. and Ullah, S. (2014), Nurse-led cognitive screening model for older adults in primary care. Geriatrics & Gerontology International.], which has been published in final form at [doi: 10.1111/ggi.12339]. In addition, authors may also transmit, print and share copies with colleagues, provided that there is no systematic distribution of the submitted version, e.g. posting on a listserve, network or automated delivery.Aim The present study aimed to establish a nurse-led cognitive screening model for community-dwelling older adults with subjective memory complaints from seven communities in Chongqing, China, and report the findings of this model. Methods Screenings took place from July 2012 to June 2013. Cognitive screening was incorporated into the annual health assessment for older adults with subjective memory complaints in a primary care setting. Two community nurses were trained to implement the screening using the Mini-Mental State Examination and Montreal Cognitive Assessment. Results Of 733 older adults, 495 (67.5%) reported having subjective memory complaints. Of the 249 individuals who participated in the cognitive screening, 102 (41%) had mild cognitive impairment, whereas 32 (12.9%) had cognitive impairment. A total of 80 participants (78.4%) with mild cognitive impairment agreed to participate in a memory support program. Participants with cognitive impairment were referred to specialists for further examination and diagnosis; only one reported that he had seen a specialist and had been diagnosed with dementia. Conclusions Incorporating cognitive screening into the annual health assessment for older adults with subjective memory complaints was feasible, though referral rates from primary care providers remained unchanged. The present study highlights the urgent need for simple screenings as well as community-based support services in primary care for older adults with cognitive or mild cognitive impairments

Schur complement-based infinity norm bounds for the inverse of S-Sparse Ostrowski Brauer matrices

In this paper, we study the Schur complement problem of $S$-SOB matrices, and prove that the Schur complement of $S$-Sparse Ostrowski-Brauer ($S$-SOB) matrices is still in the same class under certain conditions. Based on the Schur complement of $S$-SOB matrices, some upper bound for the infinite norm of $S$-SOB matrices is obtained. Numerical examples are given to certify the validity of the obtained results. By using the infinity norm bound, an error bound is given for the linear complementarity problems of $S$-SOB matrices

Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes−liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer

Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor-derived exosomes (TEX)-Liposome-paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)-PEG, was designed, respectively. GNR-PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR-mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor-α, interlekin-6, and interferon-γ). Subsequently, TEX-Liposome-PTX preferentially accumulated in lung tissues due to autologous tumor-derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX-Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis

Exome sequencing and functional analysis identifies a novel mutation in <em>EXT1</em> gene that causes multiple osteochondromas

Multiple osteochondromas (MO) is an inherited skeletal disorder, and the molecular mechanism of MO remains elusive. Exome sequencing has high chromosomal coverage and accuracy, and has recently been successfully used to identify pathogenic gene mutations. In this study, exome sequencing followed by Sanger sequencing validation was first used to screen gene mutations in two representative MO patients from a Chinese family. After filtering the data from the 1000 Genome Project and the dbSNP database (build 132), the detected candidate gene mutations were further validated via Sanger sequencing of four other members of the same MO family and 200 unrelated healthy subjects. Immunohistochemisty and multiple sequence alignment were performed to evaluate the importance of the identified causal mutation. A novel frameshift mutation, c.1457insG at codon 486 of exon 6 of EXT1 gene, was identified, which truncated the glycosyltransferase domain of EXT1 gene. Multiple sequence alignment showed that codon 486 of EXT1 gene was highly conserved across various vertebrates. Immunohistochemisty demonstrated that the chondrocytes with functional EXT1 in MO were less than those in extragenetic solitary chondromas. The novel c.1457insG deleterious mutation of EXT1 gene reported in this study expands the causal mutation spectrum of MO, and may be helpful for prenatal genetic screening and early diagnosis of MO

Inhibition of IRAK 1/4 alleviates colitis by inhibiting TLR4/ NF-κB pathway and protecting the intestinal barrier

Interleukin-1 receptor-associated kinase 1/4 (IRAK1/4) is the main kinase of the Toll-like receptor (TLR)-mediated pathway, considered a new target for treating inflammatory diseases. Studies showed a significant correlation between TLRs and inflammatory responses in ulcerative colitis (UC). Therefore, in this study, after inducing experimental colitis in mice with 3% dextran sulfate sodium (DSS), different concentrations of IRAK1/4 inhibitors were administered intraperitoneally. Then, the disease activity index was assessed, including the degree of pathological damage, by HE staining. Subsequently, while western blotting detected the TLR4/NF-κB pathway and intestinal barrier protein expression (Zonula-1, Occludin, Claudin-1, JAM-A), real-time polymerase chain reaction (RT-PCR) detected the mRNA expression levels of IRAK1/4 and mucin1/2. Furthermore, the expression levels of Zonula-1 and occludin were detected by immunofluorescence, including the plasma FITC-dextran 4000 concentration, to evaluate intestinal barrier permeability. However, ELISA measured the expression of inflammatory factors to reflect intestinal inflammation in mice. Investigations showed that the IRAK 1/4 inhibitor significantly reduced clinical symptoms and pathological DSS-induced colitis damage in mice and then inhibited the cytoplasmic and nuclear translocation of NF-κB p65, including the phosphorylation of IκBα and reduction in downstream inflammatory factor production. Therefore, we established that the IRAK1/4 inhibitor effectively improves colitis induced by DSS, partly by inhibiting the TLR4/NF-κB pathway, reducing inflammation, and maintaining the integrity of the colonic barrier

Design, synthesis, cytotoxic activity and molecular docking studies of new 20(S)-sulfonylamidine camptothecin derivatives

20(S)-Sulfonylamidine CPT-derivatives were prepared and tested for cytotoxicity.Several analogs showed superior cytotoxic activity compared to irinotecan.Key structural features related to cytotoxicity were identified by SAR analysis.Compounds 9 and 15c interacted with Topo I-DNA by a different binding mode from CPT.These compounds are new generation CPT-derived antitumor agents.In an ongoing investigation of 20-sulfonylamidine derivatives (9, YQL-9a) of camptothecin (1) as potential anticancer agents directly and selectively inhibiting topoisomerase (Topo) I, the sulfonylamidine pharmacophore was held constant, and a camptothecin derivatives with various substitution patterns were synthesized. The new compounds were evaluated for antiproliferative activity against three human tumor cell lines, A-549, KB, and multidrug resistant (MDR) KB subline (KBvin). Several analogs showed comparable or superior antiproliferative activity compared to the clinically prescribed 1 and irinotecan (3). Significantly, the 20-sulfonylamidine derivatives exhibited comparable cytotoxicity against KBvin, while 1 and 3 were less active against this cell line. Among them, compound 15c displayed much better cytotoxic activity than the controls 1, 3, and 9. Novel key structural features related to the antiproliferative activities were identified by structure–activity relationship (SAR) analysis. In a molecular docking model, compounds 9 and 15c interacted with Topo I-DNA through a different binding mode from 1 and 3. The sulfonylamidine side chains of 9 and 15c could likely form direct hydrogen bonds with Topo I, while hydrophobic interaction with Topo I and π–π stacking with double strand DNA were also confirmed as binding driving forces. The results from docking models were consistent with the SAR conclusions. The introduction of bulky substituents at the 20-position contributed to the altered binding mode of the compound by allowing them to form new interactions with Topo I residues. The information obtained in this study will be helpful for the design of new derivatives of 1 with most promising anticancer activity.CPT (green), 9 (magenta), and 15c (blue) in the binding site of DNA-Topo-I

The chemical profiling of Salvia plebeia during different growth periods and the biosynthesis of its main flavonoids ingredients

Salvia plebeia (Lamiaceae) is a valuable medicinal plant widely distributed across Asia and Oceania. However, the composition and accumulation patterns of its active ingredients in different organs during the growth and their biosynthetic mechanism remain unknown. Therefore, we conducted metabolite profiling, transcriptomic analysis, and biological functional verification to explore the distribution, accumulation, and biosynthesis mechanisms of flavonoids in S. plebeia. We identified 70 metabolites including 46 flavonoids, 16 phenolic acids, seven terpenoids, and one organic acid, of which 21 were previously unreported in S. plebeia. Combining metabolomic-transcriptomic analysis and biological functional verification, we identified the key genes involved in biosynthesis of its main active ingredients, hispidulin and homoplantaginin, including SpPAL, SpC4H, Sp4CL2, Sp4CL5, SpCHS1, SpCHI, SpFNS, SpF6H1, SpF6OMT1, SpF6OMT2, SpUGT1, SpUGT2, and SpUGT3. Using the identified genes, we reconstructed the hispidulin and homoplantaginin biosynthesis pathways in Escherichia coli, and obtained a yield of 5.33 and 3.86 mg/L for hispidulin and homoplantaginin, respectively. Our findings provide valuable insights into the changes in chemical components in different organs of S. plebeia during different growth and harvest stages and establishes a foundation for identifying and synthesizing its active components

Inhibition of T Helper Cell Differentiation by Tacrolimus or Sirolimus Results in Reduced B-Cell Activation: Effects on T Follicular Helper Cells

The effect of immunosuppressive drugs on the generation of T follicular helper (Tfh) cells, specialized in supporting B-cell differentiation, is largely unknown. We examined whether the calcineurin inhibitor tacrolimus (TAC) and the mammalian target of rapamycin (mtor) inhibitor sirolimus (SRL) inhibit Tfh cell differentiation, and affect subsequent B-cell functions. Isolated naive T cells were polarized into Tfh-like cells in the presence of TAC or SRL. To demonstrate their functionality, we co-cultured these cells with isolated B cells in the presence of alloantigen and studied the activation and differentiation of these B cells. Tfh-like cells were defined as CD4+CXCR5+ T cells, expressing immunoinhibitory programmed death protein 1 (pd1) and inducible T-cell costimulator (icos). We found that TAC and SRL significantly inhibited Tfh-like cell differentiation. Therapeutic concentrations of TAC and SRL reduced the percentage of pd1+ and icos+ Tfh cells compared to controls. In addition, T cells grown in the presence of TAC or SRL expressed less IL-21 and provided less B-cell help. TAC and SRL both inhibited Tfh-dependent alloantigen-activated B-cell proliferation and differentiation into plasma cells and transitional B cells. In conclusion, TAC and SRL inhibited the differentiation of naive T cells into functional Tfh-like cells, a finding that can be extrapolated to immunosuppressive regimens in transplant patients