The molecular and cellular action properties of artemisinins: what has yeast told us?

Artemisinin (ART) or Qinghaosu is a natural compound possessing superior anti-malarial activity. Although intensive studies have been done in the medicinal chemistry field to understand the structure-effect relationship, the biological actions of artemisinin are poorly understood and controversial. Due to the current lack of a genetic amiable model to address this question, and an accidental finding made more than a decade ago during our initial exploratory efforts that yeast can be inhibited by artemisinin, we have since been using the baker's yeast as a model to probe the molecular and cellular properties of artemisinin and its derivatives (ARTs) in living cells.

Astragaloside IV attenuates free fatty acid-induced ER stress and lipid accumulation in hepatocytes via AMPK activation.

Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) is not completely understood, the increased influx of free fatty acids (FFAs) into the liver and the FFA-induced hepatic endoplasmic reticulum (ER) stress are two crucial pathogenic processes in the initiation and development of NAFLD. In this study we investigated the effects of astragaloside IV (AS-IV), a bioactive compound purified from Astragali Radix, on FFA-induced lipid accumulation in hepatocytes and elucidated the underlying mechanisms. Human HepG2 cells and primary murine hepatocytes were exposed to FFAs (1 mmol/L, oleate/palmitate, 2:1 ratio) with or without AS-IV for 24 h.

Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression.

The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic "readers" and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation.

Salusin-β contributes to oxidative stress and inflammation in diabetic cardiomyopathy.

Salusin-β accelerates inflammatory responses in vascular endothelial cells, and increases oxidative stress in vascular smooth muscle cells. Plasma salusin-β levels were increased in diabetic patients. This study was designed to determine whether salusin-β is involved in the pathogenesis of diabetic cardiomyopathy (DCM), and whether knockdown of salusin-β attenuates cardiac inflammation and oxidative stress in rats with DCM.

Peripheral blood T-helper cells and eosinophil populations in patients with atopic and nonatopic chronic rhinosinusitis.

Background: Analysis of recent research indicated that T-helper cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP).

Objective: The purpose of this study was to investigate the peripheral blood Th1 and Th2 cells and eosinophil population in patients with CRS.

Methods: Peripheral blood samples were obtained from nine nonatopic controls, 37 patients with CRSsNP, and 66 patients with CRSwNP.

Silencing salusin-β attenuates cardiovascular remodeling and hypertension in spontaneously hypertensive rats.

Salusin-β is a bioactive peptide involved in vascular smooth muscle cell proliferation, vascular fibrosis and hypertension. The present study was designed to determine the effects of silencing salusin-β on hypertension and cardiovascular remodeling in spontaneously hypertensive rats (SHR). Thirteen-week-old male SHR and normotensive Wistar-Kyoto rats (WKY) were subjected to intravenous injection of PBS, adenoviral vectors encoding salusin-β shRNA (Ad-Sal-shRNA) or a scramble shRNA.

Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer.

Triple-negative breast cancers (TNBC) remain clinically challenging with a lack of options for targeted therapy. In this study, we report the development of a second-generation BET protein degrader, BETd-246, which exhibits superior selectivity, potency, and antitumor activity. In human TNBC cells, BETd-246 induced degradation of BET proteins at low nanomolar concentrations within 1 hour of exposure, resulting in robust growth inhibition and apoptosis.

Functional studies of Drosophila zinc transporters reveal the mechanism for zinc excretion in Malpighian tubules.

Background: Zinc is an essential metal involved in many physiological processes. Previous work has identified a set of zinc transporters involved in Drosophila dietary zinc absorption. However, zinc excretion and reabsorption, the other two important processes to maintain zinc homeostasis, are not as well understood.

Juvenile psammomatoid ossifying fibroma in paranasal sinus and skull base.

Conclusion: The endoscopic transnasal approach with IGS is a safe and effective technique, allowing completely resection of JPOF, with minimal morbidity and recurrence.

Objectives: JPOF is a benign but locally aggressive fibro-osseous lesion. This study presents a series of JPOF cases, involving anterior skull base and orbit, treated by endoscopic transnasal approach with image guidance system (IGS) to resect the mass completely.

Endoscopic resection of ossifying fibroma involving paranasal sinuses and the skull base in a series of 15 cases.

Conclusion: The key technical challenges in the resection of OFs are rapid removal of tumors by image-guided navigation, determining the boundary of the resection and the proper control of blood supply through the anterior or posterior ethmoidal arteries.

Objective: This study aimed to analyze the clinical data of adult patients with paranasal ossifying fibromas involving the anterior skull base and orbit. The surgical technique and indications are also discussed.

Surgical Technique for Subtrochanteric Fracture of Femur.

A 56-year-old woman had fell over herself 4 h prior to her presentation to our hospital. The diagnosis was a subtrochanteric fracture of the right femur (AO-32-A3). The patient was placed in a supine position was set up on a fracture traction table after general anesthesia.

Cholesterol pericarditis associated with rheumatoid arthritis: A rare case report.

Background: Cholesterol pericarditis (CP) is a special type of pericarditis. It is characterized by chronic pericardial effusion with high cholesterol concentration and with or without the formation of crystals in pericardial effusion.

Methods: In this case report, we described a 74-year-old male with massive pericardial effusion.

The efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis: A randomized, controlled trial.

Background: To evaluate the efficacy of fractional carbon dioxide (CO2) laser combined with luliconazole 1% cream for the treatment of onychomycosis and to compare it with that of fractional CO2 laser alone.

Methods: This was a randomized, parallel group, 2-arm, positive-controlled, single-center, superiority trial with a 1:2 allocation ratio. Sixty patients with clinical and mycological diagnosis of onychomycosis were enrolled from the Dermatology Department of the First Affiliated Hospital of Nanjing Medical University in Nanjing, China from March 2015 to May 2015.

Computed tomography and histopathological evaluation of osteitis in rabbit models with rhinosinusitis.

Conclusions: There is clear correspondence between HU and histopathological evaluation of osteitis. It is feasible to evaluate bone remodeling in rabbit models with rhinosinusitis by measuring the HU.

Objective: The objective of this study was to determine whether the HUs of rabbit CRS models can be used to objectively evaluate the degree of osteitis.

Treatment strategy for treating atrial-esophageal fistula: esophageal stenting or surgical repair?: A case report and literature review.

Introduction: Atrial-esophageal fistula (AEF) is a rare severe disease, which may be associated with radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) or intraoperative radiofrequency ablation of atrial fibrillation (IRAAF).

Clinical Findings: We reported a case of a 67-year-old man with AEF following RFCA of AF, who treated with esophageal stenting and surgical repair.

Outcomes: He was attacked by out-of-control sepsis and infectious shock after surgery and died.

NtKRP, a kinesin-12 protein, regulates embryo/seed size and seed germination via involving in cell cycle progression at the G2/M transition.

Kinesins comprise a superfamily of microtubule-based motor proteins involved in essential processes in plant development, but few kinesins have been functionally identified during seed development. Especially, few kinesins that regulate cell division during embryogenesis have been identified. Here we report the functional characterization of NtKRP, a motor protein of the kinesin-12 family.

Imaging characteristics of cerebral sparganosis with live worms.

Background And Purpose: The purpose of this study was to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) features of cerebral sparganosis to improve the accuracy of diagnosing cerebral sparganosis with medical imaging modalities.

Materials And Methods: This was a retrospective study of CT and MRI features of 12 patients with cerebral sparganosis. A comparative analysis between imaging findings, and intraoperative and postoperative pathological findings was performed.

Screening scFv antibodies against infectious bursal disease virus by co-expression of antigen and antibody in the bacteria display system.

We have previously reported an antigen and antibody co-expression (AAC) technology to demonstrate the interaction between a known antigen and antibody. To validate the co-expression system for screening antibody libraries, a single chain fragment variable(scFv)antibody library was constructed from chickens immunized with the VP2 protein of infectious bursal disease virus (IBDV). The genes of both VP2 and scFv antibodies were inserted into the pBFD-Ab-Ag vector.

Angiotensin-(1-7) abrogates angiotensin II-induced proliferation, migration and inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways.

The proliferation, migration and inflammation of vascular smooth muscle cells (VSMCs) contribute to the pathogenesis and progression of several cardiovascular diseases such as atherosclerosis and hypertension. Angiotensin (Ang)-(1-7) and Ang II are identified to be involved in regulating cardiovascular activity. The present study is designed to determine the interaction between Ang-(1-7) and Ang II on VSMCs proliferation, migration and inflammation as well as their underlying mechanisms.

Investigation of resectability degree for adenoidal surgery in OSA children with the method of computational fluid dynamics.

Conclusion: From aspect of fluid dynamics, expanding patients' nasopharyngeal coronal-sectional area to 48.3-54.7% of normal area will bring the airflow velocity back to normal in adenoidal hypertrophy children.

3D Culture Supports Long-Term Expansion of Mouse and Human Nephrogenic Progenitors.

Transit-amplifying nephron progenitor cells (NPCs) generate all of the nephrons of the mammalian kidney during development. Their limited numbers, poor in vitro expansion, and difficult accessibility in humans have slowed basic and translational research into renal development and diseases. Here, we show that with appropriate 3D culture conditions, it is possible to support long-term expansion of primary mouse and human fetal NPCs as well as NPCs derived from human induced pluripotent stem cells (iPSCs).

Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide.

Leukemia with a mixed lineage leukemia (MLL) rearrangement, which harbors a variety of MLL fusion proteins, has a poor prognosis despite the latest improved treatment options. Menin has been reported to be a required cofactor for the leukemogenic activity of MLL fusion proteins. Thus, the disruption of the protein-protein interactions between menin and MLL represents a very promising strategy for curing MLL leukemia.

Berberine Inhibits Intestinal Polyps Growth in Apc (min/+) Mice via Regulation of Macrophage Polarization.

Antitumor effect of berberine has been reported in a wide spectrum of cancer, however, the mechanisms of which are not fully understood. The aim of this study was to investigate the hypothesis that berberine suppresses tumorigenesis in the familial adenomatous polyposis (FAP) by regulating the macrophage polarization in Apc (min/+) mouse model. Berberine was given to Apc (min/+) mice for 12 weeks.

Distinct splicing signatures affect converged pathways in myelodysplastic syndrome patients carrying mutations in different splicing regulators.

Myelodysplastic syndromes (MDS) are heterogeneous myeloid disorders with prevalent mutations in several splicing factors, but the splicing programs linked to specific mutations or MDS in general remain to be systematically defined. We applied RASL-seq, a sensitive and cost-effective platform, to interrogate 5502 annotated splicing events in 169 samples from MDS patients or healthy individuals. We found that splicing signatures associated with normal hematopoietic lineages are largely related to cell signaling and differentiation programs, whereas MDS-linked signatures are primarily involved in cell cycle control and DNA damage responses.

Rhodium(iii)-catalyzed alkylation of primary C(sp(3))-H bonds with α-diazocarbonyl compounds.

Rh(iii)-catalyzed intermolecular chelation-assisted insertion of carbenes derived from α-diazocarbonyl compounds into non-acidic primary sp(3) C-H bonds, for the first time, is reported under mild reaction conditions, thus affording a good complement to previous metal-carbenoid-induced primary C(sp(3))-H insertion reactions. We believe that this method will open up a new avenue for primary sp(3) C-H functionalization with α-diazocarbonyl compounds.