The 2014 Ebola outbreak in West Africa trig-gered a global crisis. Nine countries have reported more than 20000 infection cases in total and nearly 8000 lives have been lost. The actual death toll is likely much higher than this figure; the death rate is as high as 70%, considering confirmed cases. The Ebola virus launches its destruction by shutting down the host’s innate and adaptive immune systems. The virus then replicates itself out of control and causes a cytokine storm in the host. Consequently, the host’s overdriven immune system attacks its own endothelial cells and this leads to multiple organ hemorrhagic damage, the host dies of septic shock finally. Under current circumstances where no specific interventions have shown effectiveness against the virus, our opinions are justified in applying a non-specific anti-viral approach during the incubation period of virus infection as an essential protection to put the host’s immune system into an alert state and henceforth to slow down the viral replication. When the viral infection proceeds to the terminal stage, the key factor would be applying a non-specific immune modulation approach to suppress the cytokine storm that causes multiple organ failure, in an attempt to open a time window for the host’s immune system to recover.

Breast cancer has a relatively high mortality rate in women due to recurrence and metastasis. Increasing evidence has identified a rare population of cells with stem cell-like properties in breast cancer. These cells, termed cancer stem cells (CSCs), which have the capacity for self-renewal and differentiation, contribute significantly to tumor progression, recurrence, drug resistance and metastasis. Clarifying the mechanisms regulating breast CSCs has important implications for our understanding of breast cancer progression and therapeutics. A strong connection has been found between breast CSCs and epithelial mesenchymal transition (EMT). In addition, recent studies suggest that the maintenance of the breast CSC phenotype is associated with epigenetic and metabolic regulation. In this review, we focus on recent discoveries about the connection between EMT and CSC, and advances made in understanding the roles and mechanisms of epigenetic and metabolic reprogramming in controlling breast CSC properties.

MicroRNAs (miRs) are small single-stranded RNA molecules, which function as key negative regulators of post-transcriptional modulation in almost all biological processes. Abnormal expression of microRNAs has been observed in various types of cancer including breast cancer. Great efforts have been made to identify an association between microRNA expression profiles and breast cancer, and to understand the functional role and molecular mechanism of aberrant-expressed microRNAs. As research progressed, ‘oncogenic microRNAs’ and ‘tumor suppressive microRNAs’ became a focus of interest. The potential of candidate microRNAs from both intercellular (tissue) and extracellular (serum) sources for clinical diagnosis and prognosis was revealed, and treatments involving microRNA achieved some amazing curative effects in cancer disease models. In this review, advances from the most recent studies of microRNAs in one of the most common cancers, breast cancer, are highlighted, especially the functions of specifically selected microRNAs. We also assess the potential value of these microRNAs as diagnostic and prognostic markers, and discuss the possible development of microRNA-based therapies.

Accumulating evidence has shown that the hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating breast cancer progression and metastasis. The effects of hypoxia-inducible factor 1 (HIF-1), a master regulator of the hypoxic response, have been extensively studied during these processes. In this review, we focus on the roles of HIF-1 in regulating breast cancer cell metastasis, specifically its effects on multiple key steps of metastasis, such as epithelial-mesenchymal transition (EMT), invasion, extravasation, and metastatic niche formation. We also discuss the roles of HIF-1-regulated non-coding RNAs in breast cancer metastasis, and therapeutic opportunities for breast cancer through targeting the HIF-1 pathway.

Macrophages are among the most abundant immune cells in the tumor microenvironment, where they are known as tumor-associated macrophages (TAMs). Substantial evidence indicates that TAMs generally play protumoral roles in the primary as well as metastatic sites (Noy and Pollard, 2014). TAMs are also known to interfere with several tumor therapeutic modalities, such as chemotherapy, irradiation, and immunotherapy. In general, depletion of M2-like TAMs or reprogramming them into M1-like phenotype enhances the efficacy of these therapies (Rolny et al., 2011; de Palma and Lewis, 2013; Germano et al., 2013).

Objective: To evaluate the effects of botulinum toxin type A (BTX-A) on mandible skeletal development by inducing muscle hypofunction. Methods: Four-week-old Sprague-Dawley rats (n=60) were divided into three groups: Group 1 animals served as controls and were injected with saline; Group 2 animals were injected unilaterally with BTX-A (the contralateral side was injected with saline); and Group 3 animals were injected bilaterally with BTX-A. In Group 2, the saline-injected side was designated the control side (Group 2-1), whereas the BTX-A-injected side was designated the experimental side (Group 2-2). After four weeks, the animals were sacrificed, dry skulls were prepared, and mandibles were measured. Results: In the unilateral group, the experimental side (Group 2-2) had reduced dimensions for all mandible measurements compared with the control side (Group 2-1), suggesting a local effect of BTX-A on mandible growth, likely due to muscle reduction. Conclusions: Localized BTX-A injection induced a change in craniofacial growth, and the skeletal effect was unilateral despite both sides of the mandible functioning as one unit.

Background and aims: Ingestion of paraquat (PQ), a widely used herbicide, can cause severe toxicity in humans, leading to a poor survival rate and prognosis. One of the main causes of death by PQ is PQ-induced pulmonary fibrosis, for which there are no effective therapies. The aim of this study was to evaluate the effects of rapamycin (RAPA) on inhibiting PQ-induced pulmonary fibrosis in mice and to explore its possible mechanisms. Methods: Male C57BL/6J mice were exposed to either saline (control group) or PQ (10 mg/kg body weight, intraperitoneally; test group). The test group was divided into four subgroups: a PQ group (PQ-exposed, non-treated), a PQ+RAPA group (PQ-exposed, treated with RAPA at 1 mg/kg intragastrically), a PQ+MP group (PQ-exposed, treated with methylprednisolone (MP) at 30 mg/kg intraperitoneally), and a PQ+MP+RAPA group (PQ-exposed, treated with MP at 30 mg/kg intraperitoneally and with RAPA at 1 mg/kg intragastrically). The survival rate and body weight of all the mice were recorded every day. Three mice in each group were sacrificed at 14 d and the rest at 28 d after intoxication. Lung tissues were excised and stained with hematoxylin-eosin (H&E) and Masson’s trichrome stain for histopathological analysis. The hydroxyproline (HYP) content in lung tissues was detected using an enzyme-linked immunosorbent assay (ELISA) kit. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) in lung tissues was detected by immunohistochemical staining and Western blotting. Results: A mice model of PQ-induced pulmonary fibrosis was established. Histological examination of lung tissues showed that RAPA treatment moderated the pathological changes of pulmonary fibrosis, including alveolar collapse and interstitial collagen deposition. HYP content in lung tissues increased soon after PQ intoxication but had decreased significantly by the 28th day after RAPA treatment. Immunohistochemical staining and Western blotting showed that RAPA treatment significantly down-regulated the enhanced levels of TGF-β1 and α-SMA in lung tissues caused by PQ exposure. However, RAPA treatment alone could not significantly ameliorate the lower survival rate and weight loss of treated mice. MP treatment enhanced the survival rate, but had no significant effects on attenuating PQ-induced pulmonary fibrosis or reducing the expression of TGF-β1 and α-SMA. Conclusions: This study demonstrates that RAPA treatment effectively suppresses PQ-induced alveolar collapse and collagen deposition in lung tissues through reducing the expression of TGF-β1 and α-SMA. Thus, RAPA has potential value in the treatment of PQ-induced pulmonary fibrosis.

Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

In many traditional Chinese medicine (TCM) hospitals, most patients are elderly with chronic diseases. Nosocomial bloodstream infections (nBSIs) are an important cause of morbidity and mortality. A retrospective surveillance study was performed to examine the epidemiology and microbiology of nBSIs in a TCM hospital from 2009 to 2011. A total of 482 patients with nBSIs were included in the study period. The incidence rate was 5.7/1000 admissions. Escherichia coli (25.5%) was the most common Gram-negative and coagulase-negative staphylococcus (CoNS) (14.1%) was the most common Gram-positive organism isolated. One-third of the E. coli and Klebsiella pneumoniae isolated from the nBSIs were the third-generation cephalosporin-resistant. Half of the Acinetobacter species isolates were resistant to imipenem. Of all the CoNS isolates, 90.7% were resistant to methicillin. Carbapenems and glycopeptide were the most frequently used for nBSI therapy. Only about one-third of patients (157/482) received appropriate empirical therapy. Septic shock, hemodialysis, Pitt bacteremia score >4, urinary tract infection, and appropriate empirical therapy were most strongly associated with 28-d mortality. The incidence of nBSIs was low in the TCM hospital but the proportion of nBSIs due to antibiotic-resistant organisms was high. A high Pitt bacteremia score was one of the most important risk factors for mortality in nBSIs. Therefore, the implementation of appropriate empirical therapy is crucial to improve the clinical outcome of nBSIs.

Objective: To investigate whether elevated homocysteine levels were a predictor of subsequent coronary heart disease (CHD) mortality, cardiovascular mortality or all-cause mortality in the general population by a meta-analysis. Methods: In a systematic search conducted in the databases of PubMed and Embase prior to October 2013, we identified relevant prospective observational studies evaluating the association between baseline homocysteine levels and CHD mortality, cardiovascular or all-cause mortality in the general population. Pooled adjust risk ratio (RR) and corresponding 95% confidence interval (CI) were calculated separately for categorical risk estimates and continuous risk estimates. Results: Twelve studies with 23623 subjects were included in the meta-analysis. Comparing the highest to lowest homocysteine level categories, CHD mortality increased by 66% (RR 1.66; 95% CI 1.12–2.47; P=0.012), cardiovascular mortality increased by 68% (RR 1.68; 95% CI 1.04–2.70; P=0.033), and all-cause mortality increased by 93% (RR 1.93; 95% CI 1.54–2.43; P<0.001). Moreover, for each 5 μmol/L homocysteine increment, the pooled RR was 1.52 (95% CI 1.26–1.84; P<0.001) for CHD mortality, 1.32 (95% CI 1.08–1.61; P=0.006) for cardiovascular mortality, and 1.27 (95% CI 1.03–1.55; P=0.023) for all-cause mortality. Conclusions: Elevated homocysteine levels are an independent predictor for subsequent cardiovascular mortality or all-cause mortality, and the risks were more pronounced among elderly persons.