Targeted PHA Microsphere-Loaded Triple-Drug System with Sustained Drug Release for Synergistic Chemotherapy and Gene Therapy.

The combination of paclitaxel (PTX) with other chemotherapy drugs (e.g., gemcitabine, GEM) or genetic drugs (e.

Tripeptidyl peptidase II coordinates the homeostasis of calcium and lipids in the central nervous system and its depletion causes presenile dementia in female mice through calcium/lipid dyshomeostasis-induced autophagic degradation of CYP19A1.

Tripeptidyl peptidase II (TPP2) has been proven to be related to human immune and neurological diseases. It is generally considered as a cytosolic protein which forms the largest known protease complex in eukaryotic cells to operate mostly downstream of proteasomes for degradation of longer peptides. However, this canonical function of TPP2 cannot explain its role in a wide variety of biological and pathogenic processes.

Application of PHA surface binding proteins of alkali-tolerant Bacillus as surfactants.

Amphiphilic protein has lipophilic and hydrophilic domains, displaying the potential for development as a biosurfactant. The polyhydroxyalkanoate (PHA) surface binding protein derived from Bacillus is a type of protein that has not been studied for its emulsifying properties. In this study, PHA granule-associated protein (PhaP), PHA regulatory protein (PhaQ), and PHA synthase subunit (PhaR) derived from an alkali-tolerant PHA-producing Bacillus cereus HBL-AI were found and heterologously expressed in E.

Complete genetic characterization of carbapenem-resistant , co-producing NDM-1, OXA-58, and PER-1 in a patient source.

The emergence of carbapenemase-producing spp. has been widely reported and become a global threat. However, carbapenem-resistant strains are relatively rare and without comprehensive genetic structure analysis, especially for isolates collected from human specimen.

Genome sequence of a tigecycline-resistant Acinetobacter seifertii recovered in human bloodstream infection in China.

Objectives: The phylogenetic characteristics of Acinetobacter seifertii clinical strain are not well-studied. Here, we reported one tigecycline-resistant ST1612Pasteur A. seifertii isolated from bloodstream infections (BSI) in China.

Emergence of IS26-mediated pLVPK-like virulence and NDM-1 conjugative fusion plasmid in hypervirulent carbapenem-resistant Klebsiella pneumoniae.

Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) has been widely reported and poses a global threat. However, the comprehensive genetic structure of ST11-KL64 hv-CRKP and the possible evolutionary mechanisms from a genetic structure perspective of this high-risk clone remain unclear. Here, a bla-bla-positive ST11-KL64 hv-CRKP isolate was obtained from a human bloodstream infection (BSI).

Cinobufacini retards progression of pancreatic ductal adenocarcinoma through targeting YEATS2/TAK1/NF-κB axis.

Background: Cinobufacini, a sterilized hot water extract of dried toad skin, had significant effect against several human cancers. However, there are few studies reporting the effect of cinobufacini on pancreatic cancer.

Purpose: To investigate the effects of cinobufacini on the progress of pancreatic ductal adenocarcinoma and the underlying mechanisms.

Amphiphilic Cationic Peptide-Coated PHA Nanosphere as an Efficient Vector for Multiple-Drug Delivery.

Amphiphilic core-shell (ACS) nanoparticles are gaining increasing research interest for multi-drug delivery in cancer therapy. In this work, a new cationic peptide-coated PHA nanosphere was prepared by self-assembly of a hydrophobic core of biodegradable poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) and a hydrophilic shell of fusion proteins of PHA granule-associated protein (PhaP) and cationic peptide RALA through a strong hydrophobic effect. The hydrophobic drug curcumin (Cur) was encapsulated in PHBHHx nanoparticles.

Emergence of uncommon KL38-OCL6-ST220 carbapenem-resistant strain, co-producing chromosomal NDM-1 and OXA-820 carbapenemases.

Objective: To characterize one KL38-OCL6-ST220 carbapenem-resistant strain, co-producing chromosomal NDM-1 and OXA-820 carbapenemases.

Methods: TCM strain was isolated from a bloodstream infection (BSI). Antimicrobial susceptibility tests were conducted disc diffusion and broth microdilution.

Macrophages Loaded with Fe Nanoparticles for Enhanced Photothermal Ablation of Tumors.

Magnetic iron nanoparticle-based theranostics agents have attracted much attention due to their good magnetism and biocompatibility. However, efficiently enriching tumors with iron nanoparticles to enhance the treatment effect remains a pressing challenge. Herein, based on the targeting and high phagocytosis of macrophages, an Fe nanoparticle-loaded macrophage delivery system was designed and constructed to efficiently deliver iron nanoparticles to tumors.

Lipid Dyshomeostasis and Inherited Cerebellar Ataxia.

Cerebellar ataxia is a form of ataxia that originates from dysfunction of the cerebellum, but may involve additional neurological tissues. Its clinical symptoms are mainly characterized by the absence of voluntary muscle coordination and loss of control of movement with varying manifestations due to differences in severity, in the site of cerebellar damage and in the involvement of extracerebellar tissues. Cerebellar ataxia may be sporadic, acquired, and hereditary.

Inhibition of histone acetyltransferase by naringenin and hesperetin suppresses Txnip expression and protects pancreatic β cells in diabetic mice.

Background: The damage of pancreatic β cells is a major pathogenesis of the development and progression of type 2 diabetes and there is still no effective therapy to protect pancreatic β cells clinically. In our previous study, we found that Quzhou Fructus Aurantii (QFA), which is rich in flavanones, had the protective effect of pancreatic β cells in diabetic mice. However, the underlying mechanism is still unclear.

Hesperetin, a SIRT1 activator, inhibits hepatic inflammation via AMPK/CREB pathway.

Silent mating type information regulation 2 homolog 1 (SIRT1) is an important inflammatory regulator, which epigenetically reprograms inflammation by altering the acetylation of NF-κB. Hesperetin, as a common flavonoid, has been proven to have a significant effect on acute inflammatory diseases. However, the detailed molecular mechanism by which hesperetin alleviates inflammatory response and accompanied tissue injury is poorly understood.

Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice.

Backgrounds: Mitochondria plays a critical role in the development and pathogenesis of nonalcoholic fatty liver disease (NAFLD). Neohesperidin (NHP) could lower blood glucose and prevent obesity in mice. However, the direct effect of NHP on hepatic steatosis has not been reported.

The flavonoid-rich Quzhou Fructus Aurantii extract modulates gut microbiota and prevents obesity in high-fat diet-fed mice.

Background: Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD).

Methods: C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300 mg/kg/day) for 12 weeks.

Cinobufacini Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting M1 Macrophage Polarization.

Cinobufacini is a traditional Chinese medicine used clinically that has antitumor and anti-inflammatory effects. It improves colitis outcomes in the clinical setting, but the mechanism underlying its function yet to be uncovered. We investigated the protective effects and mechanisms of cinobufacini on colitis using a dextran sulfate sodium (DSS)-induced colitis mouse model, mainly focusing on the impact of macrophage polarization.

NF-кB increases LPS-mediated procalcitonin production in human hepatocytes.

For years, procalcitonin (PCT) has been employed as a diagnostic biomarker for the severity of sepsis and septic shock, as well as for guiding the application of antibiotics. However, the molecular/cellular basis for the regulation of PCT production is not fully understood. In this study, we identified the signalling pathway by which the expression of PCT was induced by lipopolysaccharide in human hepatocytes at the mRNA and protein levels.

Lipin-1 determines lung cancer cell survival and chemotherapy sensitivity by regulation of endoplasmic reticulum homeostasis and autophagy.

Cancer cells undergo comprehensive metabolic reprogramming to meet the increased requirements of energy and building blocks for proliferation. Lipin-1, a phosphatidic acid phosphatase converting phosphatidic acid (PA) to diacylglycerol (DAG), is upregulated in lung adenocarcinoma (LUAD) cell lines and tumor tissues. In this study, we reveal high lipin-1 expression is correlated with poor prognosis of patients with LUAD.

promotes lung adenocarcinoma cell growth and metastasis by enhancing fructose utilization.

The metabolism of cancer cells is highly plastic. Cancer cells can change their preference for nutrient uptake under nutrient stress. Fructose is one of the most common carbohydrates in diet and its metabolism is also involved in the development and progression of tumors.

Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative stress and inflammation.

Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin nephrotoxicity. Astilbin, a flavonoid with anti-oxidation and anti-inflammation function, has been used to treat heavy metal induced kidney injury. In this study, we investigated the protective effects of astilbin on cisplatin-induced nephrotoxicity and its underlying mechanisms.

miR-125b regulates procalcitonin production in monocytes by targeting Stat3.

Sepsis is a leading cause of mortality in clinical infection, early identification and intervention is critical to improve its outcomes. Nonetheless, it is difficult to determine whether the cause of inflammation in patients is of bacterial origin at early stage. Procalcitonin (PCT) is considered as a promising marker in clinical laboratory test of bacterial infection.

Activation of the AMPK-ULK1 pathway plays an important role in autophagy during prion infection.

AMPK is a serine/threonine protein kinase that acts as a positive regulator of autophagy, by phosphorylating ULK1 at specific sites. A previous study demonstrated activation of the macroautophagic system in scrapie-infected experimental rodents and in certain human prion diseases, in which the essential negative regulator mTOR is severely inhibited. In this study, AMPK and ULK1 in the brains of hamsters infected with scrapie strain 263 K and in the scrapie-infected cell line SMB-S15 were analysed.

Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction.

Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear.