The Synergistic Effects of Corbicula fluminea and Sarcodia montagneana on Alleviating Systemic Inflammation and Osteoarthritis Progression.

Osteoarthritis (OA) is a progressive disease that causes pain, stiffness, and inflammation in the affected joints. Currently, there are no effective treatments for preventing the worst outcomes, such as synovitis or cartilage degradation. Sarcodia montagneana and Corbicula fluminea are common species found in the ocean or in freshwater areas. Their extracts are demonstrated to possess both antioxidative and anti-inflammatory functions. This study aimed to investigate the synergistic effects of the extracts of Sarcodia montagneana (SME) and Corbicula fluminea (FCE) on reducing local and systemic inflammation, as well as their efficacy in OA symptom relief. An in vitro monocytic LPS-treated THP-1 cell model and in vivo MIA-induced mouse OA model were applied, and the results showed that the combinatory usage of SME and FCE effectively suppressed IFN-γ and TNF-α production when THP-1 cells were treated with LPS. SME and FCE also significantly decreased the systemic TNF-α level and joint swelling and prevented the loss of proteoglycan in the cartilage within the joints of OA mice. The data shown here provide a potential solution for the treatment of osteoarthritis.

Fucoidan from Sargassum hemiphyllum inhibits infection and inflammation of Helicobacter pylori.

Having infected by Helicobacter pylori, the infection often leads to gastritis, gastric ulcer, or even gastric cancer. The disease is typically treated with antibiotics as they used to effectively inhibit or kill H. pylori, thus reducing the incidence of gastric adenoma and cancer to significant extent. H. pylori, however, has developed drug resistance to many clinically used antibiotics over the years, highlighting the crisis of antibiotic failure during the H. pylori treatment. We report here that the fucoidan from Sargassum hemiphyllum can significantly reduce the infection of H. pylori without developing to drug resistance. Fucoidan appears to be a strong anti-inflammation agent as manifested by the RAW264.7 cell model examination. Fucoidan can prohibit H. pylori adhesion to host cells, thereby reducing the infection rate by 60%, especially in post treatment in the AGS cell model assay. Mechanistically, fucoidan intervenes the adhesion of BabA and AlpA of H. pylori significantly lowering the total count of H. pylori and the level of IL-6 and TNF-α in vivo. These results all converge on the same fact that fucoidan is an effective agent in a position to protect the stomach from the H. pylori infection by reducing both the total count and induced inflammation.

Topical application of fucoidan derived from Cladosiphon okamuranus alleviates atopic dermatitis symptoms through immunomodulation.

Atopic dermatitis (AD) is a T helper (Th) 2 cell-mediated allergic disease, which features increased number of immunocytes and level of Th2-associated cytokines. Fucoidan is well known a naturally occurring agent effectively ameliorating many AD symptoms. Though these alleviative effects are exhilarating, the mechanisms behind, however, are still rather limited. In this study, we report that fucoidan derived from Cladosiphon okamuranus (FT) inhibits nitric oxide (NO) production by exerting its anti-inflammatory ability. Topical application on animals show that FT promotes skin repair, reduces immunocyte proliferation, and decreases serum IgE level. In histological analysis, FT favorably reduces epidermal hyperplasia and eosinophilic infiltration. The pharmacodynamics mechanism of FT is determined by means of down-regulating AD-associated cytokines (IL-4, IL-5, IL-22, IL-33, and TSLP) and up-regulating TGF-ß1 level. Moreover, FT can regulate systemic immunity by enhancing tolerogenic dendritic cells (Tol-DCs) to activate regulatory T cells (Treg) differentiation and to decrease the population of Th22 and memory B cells. Overall, topical application of FT is able to enhance Treg secreting TGF-ß1 and to down-regulate Th2 cell-mediated immunity so that AD symptoms are significantly alleviated. Thereby, FT is an ideal drug candidate potentially replacing or complementing corticosteroids to be developed and used as a therapeutic agent to treat AD.

Immunomodulation and mechanisms of fucoidan from Cladosiphon okamuranus ameliorates atopic dermatitis symptoms.

Atopic dermatitis (AD) is a long-term allergic skin disorder that occurs most frequently in children. Currently, the common treatment of AD is corticosteroids; however, the drugs cause serious side effects. Therefore, there are many patients who seek complementary and alternative treatments such as healthy food. We report that fucoidan from Cladosiphon okamuranus (COP) exhibit exceptional immuno-modulatory effects significantly improving atopic dermatitis (AD) at both in vitro and in vivo levels: First, we performed the P815 cell degranulation assay, of which the results revealed that COP possesses anti-degranulation activity suggesting COP is very conducive to relieving allergic reactions of AD. Next, we performed the animal model examination, of which AD was significantly improved, suggesting COP can focally and globally modulate the immune systems of animals. The systemic improvements were manifested clearly by decreased epidermal hyperplasia, reduced infiltration of eosinophils, and decreased expression of AD-associated cytokines. Notably, COP reduced epidermal hyperplasia by downregulating the expression of IL-22. COP displayed therapeutic effects, which is comparable to corticosteroids but lack corticosteroid side effects, such as weight loss in our animal study. COP is multitudinous immunomodulatory abilities to serve as a healthy food supplement at the current stage, not least beneficial to atopic dermatitis.

People with HIV infection had lower bone mineral density and increased fracture risk: a meta-analysis.

A meta-analysis to investigate the difference in fracture risk between individuals with and without HIV infection was performed. People living with HIV had lower bone mineral density (BMD) and greater risks of overall fractures and fragility fractures. Reducing fragility and maintaining skeletal strength for PLWH are urgently needed for this population. PURPOSE: The introduction of effective antiretroviral therapy increased the life expectancy of people living with HIV (PLWH). This population now faces problems related to aging such as decreased bone mineral density (BMD) and increased fracture risk. Some antiretroviral therapies may also negatively impact bone health. We performed a meta-analysis to investigate the difference in the fracture risk between individuals with and without HIV infection. METHODS: We compared BMD, risk of fragility fracture, and risk of all fracture between the two groups. This study included 35 articles with 106,994 PLWH and 228,794,335 controls. RESULTS: PLWH had lower lumbar spine and hip BMD than controls. PLWH had a higher prevalence of all fracture events (4.08% versus 0.44%) and fragility fractures (2.66% versus 2.19%). The relative risks of all and fragility fractures of PLWH were 1.91 (95% confidence interval (CI), 1.46-2.49; p < 0.001) and 1.68 (95% CI: 1.40-2.01; p < 0.001). PLWH also had more vertebral fractures (1.26% versus 0.37%; RR, 1.97; 95% CI: 1.22-3.2; p < 0.05), hip fractures (1.38% versus 0.81%; RR, 1.88; 95% CI: 0.99-3.57; p = 0.05), and wrist fractures (1.38% versus 1.29%; RR, 1.67; 95% CI: 1.13-2.45; p < 0.05) than healthy controls. The pooled incidence of fractures was 1.72 per 100 person-years in PLWH and 1.29 in healthy controls. CONCLUSION: PLWH had lower BMD and greater risks of all fractures and fragility fractures. Reducing fragility and maintaining skeletal strength for PLWH are urgently needed for this population.

Positive Effects of Preventive Nutrition Supplement on Anticancer Radiotherapy in Lung Cancer Bearing Mice.

(1) Background: Radiotherapy (RT) is one of the major treatments for non-small cell lung cancer, but RT-associated toxicities usually impede its anticancer effect. Nutrient supplementation has been applied for cancer prevention or a complementary measure to anticancer therapy. Here, we explored the influence of total nutrition supplementation before and after cancer occurrence on the anticancer benefit and side effects of RT. (2) Methods: C57BL/6JNarl mice were inoculated with Lewis lung carcinoma cells and then treated with radiotherapy. TNuF, a total nutrition formula, was prescribed by oral gavage. In the preventive groups, TNuF supplementation started from seven days before tumor inoculation. In the complementary groups, TNuF supplementation began after tumor inoculation. (3) Results: TNuF successfully enhanced the anticancer effect of RT against primary tumor and lung metastasis. Additionally, the complementary supplement improved the high serum TNF-α level and the wasting of sartorius muscle in mice receiving RT. In histologic and molecular analysis, TNuF was observed to modulate EGFR, apoptosis, and VEGF and PD-1/PD-L1 pathways. Furthermore, the anticancer benefit of the preventive supplement was comparable to that of the complementary administration. (4) Conclusions: Our results demonstrated that the prescription of the TNuF total nutrition formula before and after cancer diagnosis attains similar benefits in testing subjects with typical anticancer RT. TNuF is also a potential sensitizer to anti-PD-1 immune therapy.

Lipoplex-based targeted gene therapy for the suppression of tumours with VEGFR expression by producing anti-angiogenic molecules.

BACKGROUND: The anti-angiogenic fusion protein RBDV-IgG1 Fc (RBDV), which comprises the receptor-binding domain of vascular endothelial growth factor-A (VEGF-A), has shown antitumour effects by reducing angiogenesis in vivo. This study used the cationic lipoplex lipo-PEG-PEI-complex (LPPC) to simultaneously encapsulate both the RBDV targeting protein and the RBDV plasmid (pRBDV) without covalent bonds to assess VEGFR targeting gene therapy in mice with melanoma in vivo. RESULTS: LPPC protected the therapeutic transgene from degradation by DNase, and the LPPC/RBDV complexes could specifically target VEGFR-positive B16-F10 cells both in vitro and in vivo. With or without RBDV protein-targeting direction, the pRBDV-expressing RBDV proteins were expressed and reached a maximal concentration on the 7th day in the sera after transfection in vivo and significantly elicited growth suppression against B16-F10 melanoma but not IgG1 control proteins. In particular, LPPC/pRBDV/RBDV treatment with the targeting molecules dramatically inhibited B16-F10 tumour growth in vivo to provide better therapeutic efficacy than the treatments with gene therapy with IgG1 protein targeting or administration of a protein drug with RBDV. CONCLUSIONS: The simultaneous combination of the LPPC complex with pRBDV gene therapy and RBDV protein targeting might be a potential tool to conveniently administer targeted gene therapy for cancer therapy.

The Combination of Astragalus membranaceus and Angelica sinensis Inhibits Lung Cancer and Cachexia through Its Immunomodulatory Function.

Lung cancer and its related cachexia are the leading cause of cancer death in the world. In this study, we report the inhibitory effect of the combined therapy of Astragalus membranaceus and Angelica sinensis, on tumor growth and cachexia in tumor-bearing mice. Lewis lung carcinoma cells were inoculated into male C57BL/6 and CAnN.Cg-Foxn1nu nude mice. After tumor inoculation, mice were fed orally by the combination of AM and AS in different doses. In C57BL/6 mice, the combination of AM and AS significantly inhibited the growth of cancer tumor and prevented the loss of body weight and skeletal muscle. It also diminished the formation of free radicals and cytokines, stimulated the differentiation of NK and Tc cells, and rebalanced the ratios of Th/Tc cells, Th1/Th2 cytokines, and M1/M2 tumor-associated macrophages. The herbal combination also downregulated the expression of NFκΒ, STAT3, HIF-1α, and VEGF in tumors. In contrast, the findings were not observed in the nude mice. Therefore, the combination of AM and AS is confirmed to inhibit the progression of lung cancer, cancer cachexia, and cancer inflammation through the immunomodulatory function.

Antitumor, Inhibition of Metastasis and Radiosensitizing Effects of Total Nutrition Formula on Lewis Tumor-Bearing Mice.

Non-small-cell lung cancer (NSCLC) causes high mortality. Radiotherapy is an induction regimen generally applied to patients with NSCLC. In view of therapeutic efficacy, the outcome is not appealing in addition to bringing about unwanted side effects. Total nutrition is a new trend in cancer therapy, which benefits cancer patients under radiotherapy. Male C57BL/6JNarl mice were experimentally divided into five groups: one control group, one T group (borne with Lewis lung carcinoma but no treatment), and three Lewis lung carcinoma-bearing groups administrated with a total nutrition formula (T + TNuF group), a local radiotherapy plus daily 3 Gy in three fractions (T + R group), or a combination TNuF and radiotherapy (T + R + TNuF group). These mice were assessed for their mean tumor volumes, cachectic symptoms and tumor metastasis. TNuF administration significantly suppressed tumor growth and activated apoptotic cell death in NSCLC-bearing mice under radiation. The body-weight gain was increased, while the radiation-induced cachexia was alleviated. Analysis of mechanisms suggests that TNuF downregulates EGFR and VEGF signaling pathways, inhibiting angiogenesis and metastasis. In light of radiation-induced tumor cell death, mitigation of radiation-induced cachexia and inhibition of tumor cell distant metastasis, the combination of TNuF and radiotherapy synergistically downregulates EGFR and VEGF signaling in NSCLC-bearing mice.

The concurrent treatment of Scutellaria baicalensis Georgi enhances the therapeutic efficacy of cisplatin but also attenuates chemotherapy-induced cachexia and acute kidney injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin is an important chemotherapy to lung cancer, but it usually induces severe cachexia and acute kidney injury in patients. Scutellaria baicalensis Georgi (SB), commonly known as a skullcap, is a popular Chinese herbal medicine mainly used to treat inflammation, infection, and malignancy. In this study, we report the synergic effect of SB and cisplatin to Lewis lung carcinoma (LLC) cells, and the ameliorative effect of SB to cisplatin-induced cachexia and acute kidney injury. MATERIALS AND METHODS: The extract of SB was applied by water boiling and lyophilization. The MTS assay was used to exam the in-vitro effects of SB and cisplatin on the LLC viability. In the animal experiment, male C57BL/6J mice were inoculated with LLC cells, and then treated by cisplatin intraperitoneally and the SB extract orally. Tumor volume, weights of tumor, murine body, white adipose tissue and gastrocnemius muscle, as well as serum levels of BUN and creatinine were measured during the experiment. Murine kidney sample was observed after the H&E and annexin V staining. RESULTS: SB provided an enhancement of cisplatin action to inhibit tumor growth in vitro and in vivo. In the animal experiment, SB improved the loss of murine body weight and gastrocnemius muscle, the elevating BUN level, and the apoptosis of renal tubular cells in mice receiving cisplatin therapy. Meanwhile, the current treatment of SB did not further interfere with the blood cell counts of mice receiving chemotherapy. CONCLUSION: SB can enhance the anti-cancer effect of cisplatin. It also attenuates cisplatin-induced cachexia and acute kidney injury.

Specific drug delivery efficiently induced human breast tumor regression using a lipoplex by non-covalent association with anti-tumor antibodies.

BACKGROUND: A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h. RESULTS: Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model. CONCLUSIONS: LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.

Human Kinase/Phosphatase-Wide RNAi Screening Identified Checkpoint Kinase 2 as a Cellular Factor Facilitating Japanese Encephalitis Virus Infection.

Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, causes acute encephalitis in humans with high mortality. Not much is known about the interactions between viral and cellular factors that regulate JEV infection. By using a kinase/phosphatase-wide RNAi screening approach, we identified a cell cycle-regulating molecule, checkpoint kinase 2 (CHK2), that plays a role in regulating JEV replication. JEV infection induced G1 arrest and activated CHK2. Inactivation of CHK2 and its upstream ataxia-telangiectasia mutated kinase in JEV-infected cells by using inhibitors reduced virus replication. Likewise, JEV replication was significantly decreased by knockdown of CHK2 expression with shRNA-producing lentiviral transduction. We identified CHK2 as a cellular factor participating in JEV replication, for a new strategy in addressing JEV infection.

Blockade of ITGA2 Induces Apoptosis and Inhibits Cell Migration in Gastric Cancer.

BACKGROUND: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration. Integrin α2ß1 is over-expressed on a variety of cancer cells, but is low or absent in most normal organs and resting endothelial cells. RESULTS: In this report, we assessed the ITGA2 as the potential therapeutic target with the bioinformatics tools from the TCGA dataset in which composed of 375 gastric cancer tissues and 32 gastric normal tissues. According to the information from the Cancer Cell Line Encyclopedia (CCLE) database, the AGS cell line with ITGA2 high expression and the SUN-1 cell line with low expression were chosen for the further investigation. Interestingly, the anti-ITGA2 antibody (at 3 µg/ml) inhibited approximately 50% survival of the AGS cells (over-expressed ITGA2), but had no effect in SNU-1 cells (ITGA2 negative). The extents of antibody-mediated cancer inhibition positively correlated with the expression levels of the ITGA2. We further showed that the anti-ITGA2 antibody induced apoptosis by up-regulating the RhoA-p38 MAPK signaling to promote the expressions of Bim, Apaf-1 and Caspase-9, whereas the expressions of Ras and Bax/Bcl-2 were not affected. Moreover, blocking ITGA2 by the specific antibody at lower doses also inhibited cell migration of gastric cancer cells. Blockade of ITGA2 by a specific antibody down-regulated the expression of N-WASP, PAK and LIMK to impede actin organization and cell migration of gastric cancer cells. CONCLUSIONS: Here, we showed that the mRNA expression levels of ITGA2 comparing to normal tissues significantly increased. In addition, the results revealed that targeting integrin alpha 2 subunit by antibodies did not only inhibit cell migration, but also induce apoptosis effect on gastric cancer cells. Interestingly, higher expression level of ITGA2 led to significant effects on apoptosis progression during anti-ITGA2 antibody treatment, which indicated that ITGA2 expression levels directly correlate with their functionality. Our findings suggest that ITGA2 is a potential therapeutic target for gastric cancer.

Helicobacter pylori-derived heat shock protein 60 increases the induction of regulatory T-cells associated with persistent infection.

Local Treg responses are involved in Helicobacter pylori-related inflammation and clinical outcomes after infection, and H. pylori-derived HSP60 (HpHSP60) is an important virulence factor associated with gastric carcinogenesis. This study to investigate the role of HpHSP60 in immunosuppression, particularly with regard to whether it could induce the production of Treg cells. For this purpose, human peripheral blood mononuclear cells (PBMCs) were treated with or without HpHSP60 in the presence of an anti-CD3 mAb to determine the effect of HpHSP60 on cell proliferation. In this report, HpHSP60 decreased the expression of CDK4 to significantly arrest the proliferation of mitogen-stimulated T-cells, which correlated with the induction of Treg cells. Moreover, monocytic cells were essential for the induction of HpHSP60-induced Treg cells via the secretion of IL-10 and TGF-ß after treatment with HpHSP60. Blockage of HpHSP60 with specific monoclonal antibodies significantly reduced the colonization of H. pylori and the expression of Treg cells in vivo. Overall, our results suggest that HpHSP60 could act on macrophages to trigger the expression of IL-10 and TGF-ß, thereby leading to an increase in Treg cells and inhibition of T-cell proliferation.

The inhibitory effect of 7,7″-dimethoxyagastisflavone on the metastasis of melanoma cells via the suppression of F-actin polymerization.

7,7″-Dimethoxyagastisflavone (DMGF), a biflavonoid isolated from Taxus × media cv. Hicksii, induces apoptotic and autophagic cell death. However, whether DMGF suppresses tumor metastasis is unclear. The aim of this study was to investigate the anti-metastatic activities of DMGF on the metastatic processes of melanoma cells in vivo and in vitro. A transwell assay showed that DMGF could effectively attenuate the motility of B16F10 cells, and the results of real-time PCR revealed that DMGF also suppressed the expressions of matrix metalloproteinase-2 (MMP-2). Moreover, DMGF did not influence tube formation but inhibited the migration of endothelial cells. Furthermore, animal models were used to monitor the effects of DMGF on tumor metastasis, and all models showed that DMGF significantly suppressed the metastatic behaviors of B16F10 cells, including intravasation, colonization, and invasion of the lymphatic duct. In addition, DMGF could also reduce the densities of the blood vessels in the tumor area in vivo. Further investigation of the molecular mechanisms of anti-metastatic activity revealed that DMGF can down-regulate the levels of key modulators of the Cdc42/Rac1 pathway to interfere in F-actin polymerization and suppress the formation of lamellipodia by reducing the phosphorylation of CREB. These data suggested that DMGF presents anti-metastatic activities in B16F10 melanoma cells. Here, we demonstrated that DMGF can inhibit the metastasis of highly invasive melanoma cancer cells through the down-regulation of F-actin polymerization. Considering these findings, DMGF may be further developed to serve as a chemoprevention drug for patients with metastatic melanoma.

Association of In-Hospital Mortality and Dysglycemia in Septic Patients.

BACKGROUND: The associations between dysglycemia and mortality in septic patients with and without diabetes are yet to be confirmed. Our aim was to analyze the association of diabetes and sepsis mortality, and to examine how dysglycemia (hyperglycemia, hypoglycemia and glucose variability) affects in-hospital mortality of patients with suspected sepsis in emergency department (ED) and intensive care units. METHODS: Clinically suspected septic patients admitted to ED were included, and stratified into subgroups according to in-hospital mortality and the presence of diabetes. We analyzed patients' demographics, comorbidities, clinical and laboratory parameters, admission glucose levels and severity of sepsis. Odds ratio of mortality was assessed after adjusting for possible confounders. The correlations of admission glucose and CoV (blood glucose coefficients of variation) and mortality in diabetes and non-diabetes were also tested. RESULTS: Diabetes was present in 58.3% of the patients. Diabetic patients were older, more likely to have end-stage renal disease and undergoing hemodialysis, but had fewer malignancies, less sepsis severity (lower Mortality in Emergency Department Sepsis Score), less steroid usage in emergency department, and lower in-hospital mortality rate (aOR:0.83, 95% CI 0.65-0.99, p = 0.044). Hyperglycemia at admission (glucose≥200 mg/dL) was associated with higher risks of in-hospital mortality among the non-diabetes patients (OR:1.83 vs. diabetes, 95% CI 1.20-2.80, p = 0.005) with the same elevated glucose levels at admission. In addition, CoV>30% resulted in higher risk of death as well (aOR:1.88 vs. CoV between 10 and 30, 95%CI 1.24-2.86 p = 0.003). CONCLUSIONS: This study indicates that while diabetes mellitus seems to be a protective factor in sepsis patients, hyper- or hypoglycemia status on admission, and increased blood glucose variation during hospital stays, were independently associated with increased odds ratio of mortality.

Development and validation of a parsimonious and pragmatic CHARM score to predict mortality in patients with suspected sepsis.

BACKGROUND: We aimed to derive and validate a parsimonious and pragmatic clinical prediction rule using the concepts of Predisposition, Infection, Response, and Organ Dysfunction to predict in-hospital mortality; and to compare it with other prediction rules, as well as with conventional biomarkers for evaluating the mortality risk of patients with suspected sepsis in the emergency department (ED). METHODS: We conducted a pragmatic cohort study with consecutive ED patients aged 18 or older with documented diagnostic codes of infection and two sets of blood culture ordered by physicians between 2010 and 2012 in a tertiary teaching hospital. RESULTS: 7011 and 12,110 patients were included in the derivation cohort and the validation cohort for the final analysis. There were 479 deaths (7%) in the derivation cohort and 1145 deaths (9%) in the validation cohort. Independent predictors of death were absence of Chills (odds ratio: 2.28, 95% confidence interval: 1.75-2.97), Hypothermia (2.12, 1.57-2.85), Anemia (2.45, 1.97-3.04), wide Red cell Distribution Width (RDW) (3.27, 2.63-4.05) and history of Malignancy (2.00, 1.63-2.46). This novel clinical prediction rule (CHARM) performed well for stratifying patients into mortality risk groups (sensitivity: 99.4%, negative predictive value 99.7%, receiver operating characteristic area 0.77). The CHARM score also outperformed the other scores or biomarkers such as PIRO, SIRS, MEDS, CURB-65, C-reactive protein, procalcitonin and lactate (all p<.05). CONCLUSIONS: In patients with suspected sepsis, this parsimonious and pragmatic model could be utilized to stratify the mortality risk of patients in the early stage of sepsis.

STROBE-compliant article: Blood Transfusions within the First 24 Hours of Hospitalization Did Not Impact Mortality Among Patients with Severe Sepsis.

Transfusion of packed red blood cells is common during resuscitation of critically ill patients. However, the association between in-hospital mortality and blood transfusion among patients with severe sepsis during the first 24  hours of hospitalization has not yet been determined. A cohort study was conducted of adult nontrauma patients who visited the emergency department of a tertiary hospital and were diagnosed with severe sepsis. Propensity score (PS) matching was conducted, based on patient demographics, underlying illnesses, laboratory results, and vital signs presented at the emergency department, and multivariate logistic regression was performed to adjust for potential residual confounding between the 2 transfused and nontransfused groups to assess the risk of in-hospital mortality. Of 3448 patients included in this study, 265 underwent blood transfusion during the first 24  hours of hospitalization. Despite comparable severity of sepsis, patients who received transfusions tended to have lower mean arterial pressures (86 vs 98  mmHg) and hemoglobin levels (7.6 vs 11.2  g/dL), and were more likely to have chronic kidney disease (12% vs 6%) and hematologic organ dysfunction (57% vs 35%, all P < 0.001). Transfused patients tended to have higher mortality rates (26% vs 9%, respectively, P < 0.001). After PS matching, 177 pairs of transfused and nontransfused patients were analyzed. After adjusting for residual confounding factors by multivariate logistic regression in the matched patient pairs, no significant differences in in-hospital mortality were observed (odds ratio [OR] = 1.52, 95% confidence interval: 0.92-2.51). In this PS-matched cohort study of adult nontrauma patients with severe sepsis, the in-hospital mortality rate was not significantly different in patients who received blood transfusions during the first 24  hours of hospitalization.

Antrodia cinnamomea alleviates cisplatin-induced hepatotoxicity and enhances chemo-sensitivity of line-1 lung carcinoma xenografted in BALB/cByJ mice.

Whereas cisplatin (cis-diamminedichloroplatinum II) is a first-line medicine to treat solid cancerous tumors, it often causes serious side effects. New medicines that have an equivalent or even better therapeutic effect but with free or less side effects than cisplatin are highly anticipated in cancer therapy. Recent reports revealed that Antrodia cinnamomea (AC) possesses hepatoprotective activity in addition to anticancer. In this study, we wanted to know whether AC enhances chemo-sensitivity of cisplatin and/or alleviates cisplatin-induced hepatotoxicity, as well as the underlying mechanisms thereof. Our results indicated that AC inhibited proliferation of line-1 lung carcinoma cells and rescued hepatic HepG2 cells from cisplatin-induced cell death in vitro. The fact is that AC and cisplatin synergized to constrain growth of line-1 lung carcinoma cells in BALB/cByJ mice. Quantitative real-time PCR further revealed that AC promoted expression of apoptosis-related genes, while it decreased expression of NF-κB and VEGF in tumor tissues. In liver, AC reduced cisplatin-induced liver dysfunctions, liver inflammation and hepatic apoptosis in addition to body weight restoration. In summary, AC is able to increase cisplatin efficacy by triggering expression of apoptosis-related genes in line-1 lung cancer cells as well as to protect liver from tissue damage by avoiding cisplatin-induced hepatic inflammation and cell death.