Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant Staphylococcus aureus (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and β-lactam antibiotic resistance in Staphylococcus aureus. Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on β-lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of β-lactam antibiotics (e.g., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced sarA expression, and subsequently decreased mecA, and virulence-related regulators (e.g., agr RNAⅢ) and genes (e.g., fnbA and hla) expression in the studied MRSA strain. Importantly, the in vitro synergistic effect of hypericin with β-lactam antibiotic (e.g., oxacillin) translated into in vivo therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of β-lactam resistance against MRSA through sarA inhibition, and may allow us to repurpose the use of β-lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (e.g., oxacillin)

Pharmacological profile of Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus)

The female inflorescences of hops (Humulus lupulus L.), a well-known bittering agent used in the brewing industry, have long been used in traditional medicines. Xanthohumol (XN) is one of the bioactive substances contributing to its medical applications. Among foodstuffs XN is found primarily in beer and its natural occurrence is surveyed. In recent years, XN has received much attention for its biological effects. The present review describes the pharmacological aspects of XN and summarizes the most interesting findings obtained in the preclinical research related to this compound, including the pharmacological activity, the pharmacokinetics, and the safety of XN. Furthermore, the potential use of XN as a food additive considering its many positive biological effects is discussed

Analysis and Experimental Study of the Flow Characteristics in a Micro-Channel

To study the flow characteristics of low-speed fluid in a micro-channel, a model including the silk gland middle section, transition section, and forepart of a silkworm silk gland was established. The flow characteristics of silk solution therein were studied, and under the same average velocity, the flow characteristics of water were investigated for comparison with those of the silk solution. Results show that under the same average velocity, the axial velocity of the water was lower than that of the silk solution; the resistance coefficient change is the same, the resistance coefficient (both in the middle section and forepart) is constant, and in the conical channel, the resistance coefficient decreases linearly. At different average velocities, the variation of the water-related parameters was consistent; the conical channel differential pressure accounted for about 1.14% of the full differential pressure, and the straight channel pressure difference was 98.6%. With increasing outlet velocity, the shear layer of the silk solution gradually thinned, and the frictional pressure gradient decreased while the flow resistance also decreased. Later the flow characteristics of water and protein in the conical channel were studied and the changing relationship of the resistance coefficient and Reynolds number was analyzed. Finally, experimental research was undertaken on a micro-channel: the data were compared to simulated values, and the error was within 6%

Ecological Stoichiometric Characteristics of Two Typical Plantations in the Karst Ecosystem of Southwestern China

Reforestation has been widely adopted to restore soil fertility and ecosystem service function in the rocky desertification region of southwestern China. However, there has been limited research concerning the stoichiometry of carbon (C), nitrogen (N), and phosphorus (P) and nutrient resorption rate of plantations in karst ecosystems. In this study, we selected plantations of Pinus yunnanensis Franch. (PY) and Eucalyptus maideni F. Muell. (EM) in Yunnan Province. The C, N, and P concentrations and the C:N:P stoichiometry in different soil layers (0–10 cm, 10–20 cm, and 20–30 cm) were examined. The nutrient limitation and nutrient resorption efficiency were also analyzed. The leaf C and N concentrations in the PY plantation were higher than that in the EM plantation; the P concentration demonstrated the opposite trend, both in green and senesced leaves. Soil C, N, and P concentrations in the EM plantation were much greater than in the PY plantation at all three depths and decreased with the depth of the soil. In addition, the high ratios of C:P, N:P, C:Available P, and N:Available P in soil coupled with the ratios of N:P in leaves indicate that the EM plantation has a greater P deficiency than the PY plantation. In the EM plantation, the relatively low P concentrations in senesced leaves indicates efficient TP (Total phosphorus) resorption, which highlights that the high reuse proficiency of P could have favored moderating P limitation in the karst ecosystem. This research aids in understanding the stoichiometric characteristics that mediate forest properties, and provides a basis for management of vegetation in karst ecosystems

The Impacts of Vegetation Types and Soil Properties on Soil Microbial Activity and Metabolic Diversity in Subtropical Forests

Microbial functional diversity is significantly associated with both nutrient cycling and organic matter decomposition. However, how different forests as well as the soil parent materials influence the soil microbial carbon metabolism remains poorly understood. In this study, a natural secondary forest and a Pinus yunnanensis plantation, with similar climatic conditions under contrasting parent materials (clasolite in the non-karst areas and limestone in the karst areas) in Yunnan Province, China, were investigated. The soil microbial carbon metabolism diversity was assessed by the Biolog® ECO-plates. During the dry season, the soil microbial communities used carbon substrate in secondary forest and Pinus yunnanensis plantation, showing no significant difference, both in non-karst and karst areas. The microbial communities in the non-karst area were more efficient in utilizing carbon substrates than those in the karst area with the same vegetation types, resulting in the higher accumulation of organic carbon in the karst area. The six categories of most frequently utilized carbon substrates were carbohydrates, carboxylic acids, and amino acids in both the non-karst and the karst areas. The soil basal respiration of the secondary forest was higher than that of the Pinus yunnanensis plantation, both in the non-karst and the karst areas. In addition, the driving factors of the soil microbial community functional diversity in the non-karst and karst areas are different. Our findings suggest that soil microbial functional diversity is governed by vegetation types as well as by soil properties in subtropical forests. Moreover, calcareous soil holds a higher proportion of recalcitrant organic carbon, which is difficult to utilize by microorganisms

Bis(2,3-dibromo-4,5-dihydroxybenzyl) Ether, a Marine Algae Derived Bromophenol, Inhibits the Growth of Botrytis cinerea and Interacts with DNA Molecules

Bis(2,3-dibromo-4,5-dihydroxybenzyl) ether (BDDE) is a bromophenol isolated from marine algae. Previous reports have shown that BDDE possesses cytotoxic and antibacterial activity. In the present study, we demonstrate that BDDE displays broad-spectrum antifungal activities, especially on Botrytis cinerea. BDDE inhibits the growth of B. cinerea cultured on a solid medium of potato dextrose agar (PDA) as well as on the potato dextrose broth (PDB) medium. Moreover, BDDE decreases the incidence of fruit decay and severity of strawberries infected with B. cinerea. Further studies have revealed that BDDE decreases the germination rate and inhibits the mycelial growth of B. cinerea. The inhibition mechanisms are related to the disruption of the cell membrane integrity in B. cinerea spores and newly formed germ tubes. This study also suggests that BDDE possibly interacts with DNA via intercalation and minor groove binding. The studies provide evidence that BDDE has potential application in the control of gray mold after fruit harvest and the compound could serve as a candidate or lead template for rational drug design and for the development of antifungal agents

Hypericin enhances β-lactam antibiotics activity by inhibiting sarA expression in methicillin-resistant Staphylococcus aureus.

Bacteremia is a life-threating syndrome often caused by methicillin-resistant Staphylococcus aureus (MRSA). Thus, there is an urgent need to develop novel approaches to successfully treat this infection. Staphylococcal accessory regulator A (SarA), a global virulence regulator, plays a critical role in pathogenesis and β-lactam antibiotic resistance in Staphylococcus aureus. Hypericin is believed to act as an antibiotic, antidepressant, antiviral and non-specific kinase inhibitor. In the current study, we investigated the impact of hypericin on β-lactam antibiotics susceptibility and mechanism(s) of its activity. We demonstrated that hypericin significantly decreased the minimum inhibitory concentrations of β-lactam antibiotics (e.g., oxacillin, cefazolin and nafcillin), biofilm formation and fibronectin binding in MRSA strain JE2. In addition, hypericin significantly reduced sarA expression, and subsequently decreased mecA, and virulence-related regulators (e.g., agr RNAⅢ) and genes (e.g., fnbA and hla) expression in the studied MRSA strain. Importantly, the in vitro synergistic effect of hypericin with β-lactam antibiotic (e.g., oxacillin) translated into in vivo therapeutic outcome in a murine MRSA bacteremia model. These findings suggest that hypericin plays an important role in abrogation of β-lactam resistance against MRSA through sarA inhibition, and may allow us to repurpose the use of β-lactam antibiotics, which are normally ineffective in the treatment of MRSA infections (e.g., oxacillin)

KAP1 Positively Modulates Influenza A Virus Replication by Interacting with PB2 and NS1 Proteins in Human Lung Epithelial Cells

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-β production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production