Handelin alleviates cachexia- and aging-induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation.

BACKGROUND: Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. METHODS: A tumour necrosis factor (TNF)-α-induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)-treated 8-week-old model mice and 23-month-old (aged) mice were used to examine the therapeutic effects of handelin on cachexia- and aging-induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. RESULTS: Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF-α-induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin-like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin-1 expression, inhibited nuclear factor-κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS-treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross-sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti-inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant-related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL-1ß levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy. CONCLUSIONS: Handelin ameliorated cachexia- and aging-induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.

[Influence of Psychological Factors on the Quality of Life of Patients with Non-surgical Gastric Cancer].

Objective To explore the impact of pressure and social support on the quality of life of non-surgical gastric cancer patients. Methods A total of 158 non-surgical patients diagnosed with gastric cancer by gastroscopy from June to August in 2021 were included in this study.The perceived stress scale,multidimensional scale of perceived social support,and the 36-item short form health survey questionnaire [including the physical composite score (PCS) and mental composite score (MCS)] were used for the evaluation of perceived stress,social support,and quality of life,respectively.Spearman correlation analysis was conducted.Mann-Whitney U test,Kruskal-Wallis H test or one-way analysis of variance was employed for the comparison between groups.Bivariate Logistic regression was employed for multiple comparisons. Results Gender (P<0.001),marriage (P=0.022),age (P=0.022),and sickness symptoms (P=0.009) affected the PCS of non-surgical gastric cancer patients.Gender (P=0.016),income (P=0.012),and sickness symptoms (P=0.038) influenced the MCS of non-surgical gastric cancer patients.Perceived pressure was negatively correlated with PCS and MCS (all P<0.001).The three factors of social support were positively correlated with PCS and MCS (all P<0.001).The PCS was associated with gender (OR=0.219,95%CI=0.091-0.525,P=0.001),age (OR=0.969,95%CI=0.942-0.998,P=0.035),sickness symptoms (OR=1.142,95%CI=1.013-1.287,P=0.030),perceived stress (OR=0.921,95%CI=0.860-0.987,P=0.019),and family support (OR=1.195,95%CI=1.064-1.343,P=0.003).The MCS was associated with gender (OR=0.169,95%CI=0.062-0.459,P<0.001),perceived pressure (OR=0.910,95%CI=0.844-0.981,P=0.013),and other support (OR=1.136,95%CI=1.002-1.288,P=0.046). Conclusions The quality of life of the patients with non-surgical gastric cancer was related to perceived pressure and social support.Female and elderly patients have lower quality of life,which requires more attention in clinical work.

Expression of DNM3 is associated with good outcome in colorectal cancer.

The aim of this study is to reveal the potential value of dynamin3 (DNM3) in colorectal cancer (CRC) evaluation of clinical diagnosis and prognosis. A total of 100 tissue samples were collected from 50 patients with stages I-IV, CRC tissues (n = 50) paired with non-cancerous adjacent colorectal tissues (n = 50). The expression levels of DNM3 were detected in 50 cases of CRC tissues and 50 cases of non-cancerous adjacent colorectal tissues by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Immunohistochemical method (IHC) was conducted to semi-quantify the expression of DNM3 protein. Results showed that the relative expression of DNM3 mRNA in CRC tissues was 0.634-fold of that in non-cancerous adjacent colorectal tissues. The positive rate of DNM3 protein in CRC tissues (42.0%) was much lower than that in non-cancerous adjacent colorectal tissues (66.0%; P < 0.05). The expression level of DNM3 protein in CRC tissues was dependent on tumor size, degree of histological differentiation, and clinical stage (P < 0.05). The expression level of DNM3 mRNA in CRC tissues was significantly correlated with tumor size and pathology classification (P < 0.05). The research shows that detecting the expression of DNM3 helps in analyzing the tumor size, degree of histological differentiation, and clinical stage. Expression of DNM3 may be associated with good outcome in CRC.

Self-Organization Formation of Multicellular Spheroids Mediated by Mechanically Tunable Hydrogel Platform: Toward Revealing the Synergy of Chemo- and Noninvasive Photothermal Therapy against Colon Microtumor.

Three-dimensional (3D) tumor cell culture offers a more tissue-recapitulating model in cancer treatment evaluation. However, conventional models based on cell-substrate adhesion deprivation are still of insufficient real tumor mimic. In this work, a novel method is proposed for inducing multicellular spheroids (MCSs) formation based on hydrogel with tunable microenvironmental properties. Colon tumor cells DLD1 cultured on hydrogel substrate with proper physical stimulation form MCSs via self-organization. Chemotherapy based on clinical drug and far-infrared photothermal therapy is evaluated with DLD1 MCSs obtained by this method. The synergism of chemotherapy and noninvasive photothermal therapy based on graphene device is further verified in MCSs model and it is believed this method holds potential in in vitro anti-tumor strategies evaluation for precision medicine.

Self-Healable, High-Strength Hydrogel Electrode for Flexible Sensors and Supercapacitors.

Flexible energy storage materials and sensors have become the key equipment of human-machine interface technology. For the preparation of these devices, hydrogel electrodes are relevant because of their unique porous structure, high capacitance, flexibility, small size, and lightweight. In this paper, regular polypyrrole (PPy) is synthesized on a heat-induced phase-separated gel (H-Gel/AS) by the template degradation method, and a gelatin-based PPy hydrogel with high strength, high strain rate, and high conductivity is prepared. Moreover, by adding multiwalled carbon nanotubes (MWCNTs) into a gelatin solution according to the H-Gel/AS method, the electrochemical performance of the resulting H-Gel/AS-MWCNTs-PPy electrode is greatly improved. When the H-Gel/AS-MWCNTs-PPy gel is immersed in an ammonium sulfate solution, wrinkles appear on the surface, resulting in further enhancement of the capacitance. On this basis, a flexible sensor and a solid-state supercapacitor are assembled, and their performance is tested. The sensor can detect tensile, bending, and twisting strains with high sensitivity. Meanwhile, as a flexible solid-state supercapacitor, the specific capacitance is 75 F g-1, and the capacitance retention rate after 5000 cycles is 98.1% under bending conditions. More importantly, the gelatin-based hydrogel shows great potential for application in wearable devices.

Clinical study of XiangShaLiuJunZi decoction combined with S-1 as maintenance therapy for stage III or IV gastric carcinoma and colorectal carcinoma.

INTRODUCTION: S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety. OBJECTIVES: The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC. METHODS: This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment. DISCUSSION: This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16008575.

Hospitalization costs of treating colorectal cancer in China: A retrospective analysis.

BACKGROUND: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China. METHODS: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer. RESULTS: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ±â€Š13.28 years; male: 59.46%; mean age: 61.80 ±â€Š13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001). CONCLUSION: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

[A case report of EIF2AK3-related Wolcott-Rallison syndrome and literature review].

The patient was a female infant aged 1 month and 29 days. She was admitted to the hospital due to convulsions for 6 days and increased blood glucose level for 5 days. She had unstable blood glucose levels. The level of glycosylated hemoglobin was too high to measure. Urine glucose was positive (+ - ++++). The levels of fasting C-peptide and insulin were 0.19 ng/mL and 11.68 µIU/mL respectively. High-throughput sequencing of the genetic endocrine disease gene Panel (412 detected genes, including 49 known diabetes-related genes) showed that the EIF2AK3 gene in the infant had two novel compound heterozygous mutations, c.2731_2732delAG and c.2980G>A, both of which were located in the kinase domain. The infant was diagnosed with Wolcott-Rallison syndrome (WRS). As a rare autosomal recessive disease, WRS is characterized by neonatal diabetes, multiple epiphyseal dysphasia and liver disease. Neonatal diabetes is a prerequisite for the diagnosis of WRS. The EIF2AK3 gene is the pathogenic gene of WRS.

Synthesis, Crystal Structures and Catalytic Property of Dioxomolybdenum(VI) and Nickel(II) Complexes Derived from bis-Schiff Bases.

A new mononuclear dioxomolybdenum(VI) complex, [MoO2L1], and a new linear trinuclear nickel(II) complex, [NiNiL2(?1-?1:?0-OAc)(?2-?1:?1-OAc)2]·H2O, where L1 is the dianionic form of N,N'-bis(5-fluorosalicylidene)-1,3-propanediamine (H2L1), L2 is the dianionic form of N,N'-bis(5-fluoro-2-hydroxybenzylidene)-2-hydroxy-1,3-propanediamine (H2L2), have been synthesized and characterized by elemental analysis, FT-IR spectroscopy, and single-crystal X-ray determination. The Mo atom in the molybdenum complex is coordinated by four donor atoms of the Schiff base ligand, and two oxo groups, forming an octahedral coordination. In the nickel complex, there are three bridges across the Ni-Ni atom pairs, involving two phenolate O atoms of a Schiff base ligand, and an O-C-O moiety of a ?2-?1:?1-OAc group. The central Ni atom is located on an inversion center and has octahedral coordination involving four bridging O atoms from two Schiff base ligands in the equatorial plane and two O atoms from two ?2-?1:?1-OAc ligands in the axial positions. The coordination around the terminal Ni atoms is also octahedral, with two imino N and two phenolate O atoms from a Schiff base ligand defining the equatorial plane, and with two O atoms respectively from a ?1-?1:?0-OAc and a ?2-?1:?1-OAc ligands occupying the axial positions. The molybdenum complex has excellent catalytic property for sulfoxidation reactions.

Breast cancer laterality and molecular subtype likely share a common risk factor.

BACKGROUND: To investigate the epidemiological features of breast cancer laterality and molecular subtypes in southern China. MATERIALS AND METHODS: A total of 2,049 cases who were diagnosed with unilateral breast cancer in the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations. RESULTS: Breast cancer was more likely to be diagnosed in the left breast than in the right at a rate of around 5%. In the case of invasive carcinomas, the right breast was more commonly affected than the left in young (<40 years old) patients (left-to-right [L:R] ratio 0.80, 95% CI 0.65, 0.98), whereas the opposite trend was found in old (≥40 years old) patients (L:R ratio 1.06, 95% CI 1.02, 1.73). Except for invasive mucinous and invasive medullary breast cancers, the other histological types occurred more frequently on the left side than on the right. In situ cancer with a defined subtype was likely to be diagnosed as luminal B(HER-2+). Except for invasive medullary and invasive nonspecific cancers, other invasive carcinomas with a defined subtype were most likely to be diagnosed as luminal B(HER-2-). The age of ≥40 years was a risk factor for luminal B(HER-2+), and a significant correlation was present between the right breast and luminal B(HER-2+). CONCLUSION: We explored the risk factors of breast cancer laterality and various molecular subtypes and found that age may be a predictor of breast cancer laterality. We found that age and laterality are the probable risk factors of the luminal B(HER-2+) type of breast cancer. These results provide a basis for the epidemiological characterization of breast cancer.

Construction of a recombinant eukaryotic expression vector containing DNM3 gene and its expression in colon cancer cells.

INTRODUCTION: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited. MATERIALS AND METHODS: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot. RESULT: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P<0.001). DNM3 downregulated the protein expression of MMP-2 and MMP-9. CONCLUSION: DNM3 may weaken the malignant behavior of colon cancer and may have promoted the invasion and migration of colon cancer by regulating the expression of MMP-2 and MMP-9.

Addition of bevacizumab to systemic therapy for locally advanced and metastatic nasopharyngeal carcinoma.

Radiotherapy is a vital treatment option for patients with nasopharyngeal carcinoma (NPC). Concurrent cisplatin-based radiochemotherapy with or without adjuvant chemotherapy had acquired good clinical effects with good local control rates. However, a number of patients present with metastasis following systemic regimens or initial diagnosis of locally advanced NPC, which cause difficulty for subsequent therapy. Therefore, there is an urgent requirement to discover novel targeted therapies. The present report describes one case of a patient with NPC and multiple metastases. The patient was treated with systemic therapy in combination with bevacizumab, palliative radiotherapy and chemotherapy following treatment with cetuximab and concurrent chemoradiotherapy in 2015. Following the addition of bevacizumab, metastases were reduced or disappeared after >2 months, and the duration of progression-free survival was 7 months. Bevacizumab is a monoclonal antibody that targets VEGF, and it is associated with angiogenesis, which causes the growth, invasion and progression of tumors. In previous studies, bevacizumab has been approved for the treatment of several types of malignant cancer and it has been able to effectively improve prognosis. In the present review, the effect of adding bevacizumab to systemic therapy for the treatment of NPC was analyzed, with a particular focus on advanced and metastatic diseases. A growing number of phase I/II clinical trials involving bevacizumab for NPC have been conducted with clinical outcomes showing improved rates of overall survival and progression-free survival as well as improvements in the quality of life of patients. However, severe or deadly toxicities can also result from combination treatment with bevacizumab. In the future, bevacizumab may become a common addition to systemic therapy for the treatment of locally advanced and metastatic NPC.

Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma.

Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P=0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

Positive expression of Y-box binding protein 1 and prognosis in non-small cell lung cancer: a meta-analysis.

BACKGROUND: Y-box binding protein 1 (YB-1) belongs to the cold shock domain protein family involved in transcription and translation. We conducted a meta-analysis of the association between YB-1 expression and the survival and clinicopathological features in NSCLC. METHODS: PubMed and Embase were searched to identify studies that evaluated the YB-1 expression (by immunohistochemistry) and overall survival (OS) in NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CI) of OS were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software. RESULTS: Data on 692 NSCLC patients were collected from six eligible studies. Meta-analysis revealed that YB-1 was associated with worse OS (HR = 1.59, 95% CI [1.27, 2.00], P < 0.001, fixed effect), tumor stage (OR = 0.43, 95% CI [0.22-0.82], P = 0.01, random effect), and depth of invasion (OR = 0.37, 95%CI [0.22-0.63], P < 0.001, fixed effect). A subgroup was analyzed by IHC staining to determine the location of YB-1 positive expression. Poor OS was observed in nucleus staining (pooled HR = 1.86, 95% CI [1.41, 2.45], P < 0.001). However, no statistical significance was observed in combined cytoplasmic and nuclear staining (pooled HR = 1.14, 95% CI [0.76, 1.72], P = 0.536). CONCLUSIONS: Meta-analysis indicated that YB-1 overexpression is correlated with worse OS and clinicopathological features in NSCLC. Subgroup analysis revealed that the nucleus expression of YB-1 may be more closely associated with NSCLC prognosis than cytoplasmic expression.

Melanoma-Induced Anemia Could be Rescued by Sca-1+ Mesenchymal Stromal Cells in Mice.

The intrinsic basis of cancer-related anemia (CRA) is erythropoiesis disorder, which is a common complication of cancer and exerts a negative influence on the life quality of cancer patients. Cell therapy using mesenchymal stromal cells (MSCs) is considered as a promising method in cancer treatment. Furthermore, MSCs have been used to cure few type of anemia and be considered as a potential strategy to recover anemia radically. However, none reports its application in CRA treatment. In CRA model mice, we found that the number of lin-c-kit+Sca-1+ and Sca-1+ MSCs was decreased. And CRA resulted in an increased number of proerythroblasts and basophilic erythroblasts and decreased number of orthochromatic erythroblasts. Furthermore, in CRA model mice transplanted with Sca-1+ MSCs and MSCs, the levels of red blood cell count and Hb in peripheral blood were obviously increased. And the accumulation of proerythroblasts and basophilic erythroblasts was inhibited. In addition, the expression patterns of GATA-1 and GATA-2, which is pivotal to anemia, were remarkably recovered. Our results demonstrated that either MSCs or its subpopulation could effectively recover CRA erythropoiesis through GATA-1/GATA-2 signaling, which outstrips the traditional symptomatic therapy.

Anti-inflammatory effects of guggulsterone on murine macrophage by inhibiting LPS-induced inflammatory cytokines in NF-κB signaling pathway.

The present study was aimed to investigate the effects of guggulsterone (GS) on proinflammatory responses as well as the underlying molecular mechanisms in macrophage upon lipopolysaccharide (LPS) stimulation. Effects of GS on viability of Raw264.7 cells were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (PCR) was employed to examine the mRNA expression of cytokines, including interleukin 1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS). Phosphorylations of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (p38), and inhibitor of nuclear factor kappaB (IκB) were determined using immunoblotting. The results revealed that GS was not toxic to Raw264.7 cells at designated concentrations. We demonstrated that GS significantly suppressed the elevated mRNA expression of proinflammatory cytokines, including IL-1ß, TNF-α, and iNOS in a dose-dependent manner. GS treatment reduced the level of IκB phosphorylation in LPS-stimulated macrophages in a dose-dependent manner. Use of BAY 11-7082, an inhibitor of nuclear factor-kappaB (NF-κB), led to significantly suppressing effects on IL-1ß and TNF-α expression similar as that of GS-treated cells. Our findings suggest that GS possesses anti-inflammatory activity, which may be attributed to downregulation of iNOS and inhibition of NF-κB activity in LPS-stimulated Raw264.7 cells.

Expansion of a bitter taste receptor family in a polyphagous insect herbivore.

The Insect taste system plays a central role in feeding behaviours and co-evolution of insect-host interactions. Gustatory receptors form the interface between the insect taste system and the environment. From genome and transcriptome sequencing we identified 197 novel gustatory receptor (GR) genes from the polyphagous pest Helicoverpa armigera. These GRs include a significantly expanded bitter receptor family (180 GRs) that could be further divided into three categories based on polypeptide lengths, gene structure and amino acid sequence. Type 1 includes 29 bitter Gr genes that possess introns. Type 2 includes 13 long intronless bitter Gr genes, while Type 3 comprises 131 short intronless bitter Gr genes. Calcium imaging analysis demonstrated that three Type 3 GRs (HarmGR35, HarmGR50 and HarmGR195) can be activated by a crude extract of cotton leaves. HarmGR195, a GR specifically and selectively expressed in adult tarsi, showed a specific response to proline, an amino acid widely present in plant tissues. We hypothesise that the expansion in the H. armigera GR family may be functionally tied to its polyphagous behavior. Understanding the molecular basis of polyphagy may provide opportunities for the development of new environmentally friendly pest control strategies.

Sca-1(+) mesenchymal stromal cells inhibit splenic marginal zone B lymphocytes commitment through Caspase-3.

Mesenchymal stromal cells (MSCs) have been characterized as an important component of hematopoietic niche, which are capable of modulating the immune system through interaction with a wide range of immune cells. Marginal zone B cells, one main type of mature B lymphocytes, play a central role in eliciting antibody response against pathogens. However, how MSCs and its subpopulations regulate marginal zone B cells commitment is unknown yet. In this study, we assessed the contribution of Sca-1(+) MSCs on marginal zone B cells commitment. Our results showed that Sca-1(+) MSCs inhibit the commitment of marginal zone B lymphocytes. The inhibition was exerted through lowered Caspase-3 expression. Furthermore, we found marginal zone B lymphocytes in spleen of Caspase-3 knockout mice decreased and Caspase-3 knockout Sca-1(+) MSCs accounted for the MZB lymphocytes decrease. In conclusion, our investigation provided clues about Sca-1(+) MSCs regulation on the commitment of marginal zone B cells through Caspase-3 gene.

Primary Pulmonary Paraganglioma: A Case Report and Review of Literature.

Primary pulmonary paraganglioma is a rare disease. We report a case of a 37-year old female patient with space-occupying lesions in the right lower pulmonary lobe during a routine examination without any symptoms. The patient underwent video-assisted thoracoscopic surgery (VATS) resection of the right middle lobe and dissection of hilar and mediastinal lymph nodes under general anesthesia. She recovered without recrudescence. Preoperative diagnosis is difficult. Accurate diagnosis requires pathological examination, and immunohistochemical test is particularly important. Complete resection is the first treatment option for solitary primary pulmonary paraganglioma; however, VATS is a better technique. Given the high local control rates and few complications of radiotherapy, it is considered as a standard treatment.

Sca1(+) mesenchymal stromal cells inhibit graft-versus-host disease in mice after bone marrow transplantation.

Mesenchymal stromal cells (MSCs) have therapeutic potential for the prevention and treatment of graft-versus-host disease (GVHD). However, MSCs comprise several subpopulations, which have not been individually assessed for their role in GVHD suppression. In this study, we assessed the immunosuppressive effect of bone-related Sca1(+) MSCs on acute GVHD in a MHC-mismatched mouse model of allogeneic hematopoietic stem cell transplantation (HCT). Our results showed that Sca1(+) MSCs decreased the severity of acute GVHD (aGVHD) and prolonged the survival period of allogeneic HCT recipients. This effect was exerted through lowered T lymphocyte infiltration in target organs and by inhibition of CD80/86 expression on host dendritic cells. Furthermore, the expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a negative regulator of T cells, was elevated in the recipient splenocytes. In conclusion, bone-related Sca1(+) MSCs subpopulation suppressed GVHD and could be a novel treatment for acute GVHD.