CXCR4-Mediated Codelivery of FLT3 and BCL-2 Inhibitors for Enhanced Targeted Combination Therapy of FLT3-ITD Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is often associated with poor prognosis and survival. Small molecule inhibitors, though widening the treatment landscape, have limited monotherapy efficacy. The combination therapy, however, shows suboptimal clinical outcomes due to low bioavailability, overlapping systemic toxicity and drug resistance.

A theoretical study on toluene oxidization by OH radical.

Toluene, a prominent member of volatile organic compounds (VOCs), exerts a substantial adverse influence on both human life and the environment. In the context of advanced oxidation processes, the ·OH radical emerges as a highly efficient oxidant, pivotal in the elimination of VOCs. This study employs computational quantum chemistry methods (G4MP2//B3LYP/6-311++G(d,p)) to systematically investigate the degradation of toluene by ·OH radicals in an implicit solvent model, and validates the rationale of choosing a single-reference method using T1 diagnostics.

Pathological features and molecular signatures of early olfactory dysfunction in 3xTg-AD model mice.

Background: Olfactory dysfunction is known to be an early manifestation of Alzheimer's disease (AD). However, the underlying mechanism, particularly the specific molecular events that occur during the early stages of olfactory disorders, remains unclear.

Methods: In this study, we utilized transcriptomic sequencing, bioinformatics analysis, and biochemical detection to investigate the specific pathological and molecular characteristics of the olfactory bulb (OB) in 4-month-old male triple transgenic 3xTg-AD mice (PS1M146V/APPSwe/TauP301L).

Antibody-Mediated Nanodrug of Proteasome Inhibitor Carfilzomib Boosts the Treatment of Multiple Myeloma.

Multiple myeloma (MM) is the second most common hematological malignancy. For relapsed and refractory MM, a proteasome inhibitor, carfilzomib (CFZ), has become one of the few clinical options. CFZ suffers, nevertheless, metabolic instability and poor bioavailability and may induce severe cardiovascular and renal adverse events.

Integrated transcriptomics reveals the brain and blood biomarkers in Alzheimer's disease.

Background: The systematic molecular associations between the peripheral blood cells and brain in Alzheimer's disease (AD) remains unclear, which hinders our understanding of AD pathological mechanisms and the exploration of new diagnostic biomarkers.

Methods: Here, we performed an integrated analysis of the brain and peripheral blood cells transcriptomics to establish peripheral biomarkers of AD. By employing multiple statistical analyses plus machine learning, we identified and validated multiple regulated central and peripheral network in patients with AD.

Removal and Recovery of Gaseous Elemental Mercury Using a Cl-Doped Protonated Polypyrrole@MWCNTs Composite Membrane.

Due to the restrictions on mercury mining, recovering the mercury from mercury-containing waste is attracting increasing attention. This study successfully achieved the removal and recovery of gaseous elemental mercury (Hg) by using membrane technology. A novel composite membrane of Cl-doped protonated polypyrrole-coated multiwall carbon nanotubes (Cl-PPy@MWCNTs) was fabricated in which MWCNTs acted as the framework to support the active component Cl-PPy.

Risk Factors for Outcomes After Microvascular Decompression for Trigeminal Neuralgia.

Background: Microvascular decompression (MVD) has been the most effective long-term surgical treatment of trigeminal neuralgia (TN). However, the risk factors for poor pain control after MVD are not fully understood.

Methods: A total of 184 patients with typical TN who had undergone MVD at our institution from January 3, 2008 to January 3, 2016 were enrolled in the present study.

Stereotactic Catheter Drainage Versus Conventional Craniotomy for Severe Spontaneous Intracerebral Hemorrhage in the Basal Ganglia.

Intracerebral hemorrhage (ICH) is one of the most devastating forms of cerebrovascular pathology. However, its treatment remains a matter of debate among neurosurgeons and neurologists. The study was to explore the efficacy of minimally invasive surgery (stereotactic catheter drainage, SCD) for patients with severe intracerebral hemorrhage (Glasgow Coma Scale, GCS) score ≤ 8 and hematoma volume ≥ 30 cm3) and to determine predisposing factors for good clinical outcome.

Combustion behavior, emission characteristics of SO, SO and NO, and in situ control of SO and NO during the co-combustion of anthracite and dried sawdust sludge.

The combustion behaviors of anthracite and dried sawmill sludge (DSS) were studied using thermogravimetric analysis (TGA) and derivative thermogravimetric analysis (DTG). DSS was found to be a promoter for anthracite combustion, the addition of DSS in anthracite decreased the burnout temperature and time. But DSS caused the rapid releases of SO and NO in the initial combustion stage.

The Clinical Efficacy of Electromagnetic Navigation-Guided Hematoma Puncture Drainage in Patients with Hypertensive Basal Ganglia Hemorrhage.

Objective: To investigate the clinical efficacy of navigation-guided minimally invasive surgery in patients with hypertensive basal ganglia hemorrhage.

Methods: A total of 64 patients with hypertensive basal ganglia hemorrhage were enrolled in this retrospective study. They were divided into a navigation group and a traditional group based on surgical approaches.

Two occurrences of delayed epidural hematoma in different areas following decompressive craniectomy for acute subdural hematoma in a single patient: a case report.

Background: Delayed epidural hematoma (DEH) following evacuation of traumatic acute subdural hematoma (ASDH) or acute epidural hematoma (EDH) is a rare but devastating complication, especially when it occurs sequentially in a single patient.

Case Presentation: A 19-year-old man who developed contralateral DEH following craniotomy for evacuation of a traumatic right-side ASDH and then developed a left-side DEH of the posterior cranial fossa after craniotomy for evacuation of the contralateral DEH. He was immediately returned to the operating room for additional surgeries and his neurological outcome was satisfactory.

Detection of specific Chlamydia pneumoniae and cytomegalovirus antigens in human carotid atherosclerotic plaque in a Chinese population.

To explore the relationship between certain pathogens, such as chlamydia pneumonia (Cpn) and cytomegalovirus (CMV), and carotid atherosclerosis (AS) in a Chinese population.Twenty-five carotid atherosclerotic stenosis patients from the Beijing Tiantan Hospital (affiliated with Capital Medical University) participated in the study. After undergoing digital subtraction angiography (DSA) and/or computed tomography angiography (CTA), the degree of carotid artery stenosis was over 70% in all cases, and the patients underwent carotid endarterectomy.

Long non-coding RNA in glioma: signaling pathways.

Glioma is regarded as the most prevalent malignant carcinoma of the central nervous system. Thus, the development of new therapeutic strategies targeting glioma is of significant clinical importance. Long non-coding RNAs (lncRNAs) are functional RNA molecules without a protein-coding function and are reportedly involved in the initiation and progression of glioma.

Management of screwdriver-induced penetrating brain injury: a case report.

Background: Penetrating brain injury (PBI) can be caused by several objects ranging from knives to chopsticks. However, an assault with long and electric screwdriver is a peculiar accident and is relatively rare. Because of its rarity, the treatments of such injury are complex and nonstandardized.

Review: Traumatic brain injury and hyperglycemia, a potentially modifiable risk factor.

Hyperglycemia after severe traumatic brain injury (TBI) occurs frequently and is associated with poor clinical outcome and increased mortality. In this review, we highlight the mechanisms that lead to hyperglycemia and discuss how they may contribute to poor outcomes in patients with severe TBI. Moreover, we systematically review the proper management of hyperglycemia after TBI, covering topics such as nutritional support, glucose control, moderated hypothermia, naloxone, and mannitol treatment.

Regulation of the HMOX1 gene by the transcription factor AP-2δ with unique DNA binding site.

AP-2 transcription factors are important sequence-specific DNA-binding regulators that are expressed in the neural crest and other tissues during mammalian development. The human AP-2 family of transcription factors consists of five members, AP-2α, -β, -γ, -δ and -ε, which have an important role in the regulation of gene expression during development and in the differentiation of multiple organs and tissues. The present study aimed to investigate the mechanism by which AP-2δ mediates heme oxygenase-1 (HMOX1) gene expression.

Cloning, expression and biochemical characterization of a novel, moderately thermostable GDSL family esterase from Geobacillus thermodenitrificans T2.

A thermostable GDSL family esterase-encoding gene, EstL5, was directly obtained from the genomic DNA of Geobacillus thermodenitrificans T2. Recombinant hexahistidine-tagged EstL5 was overexpressed, purified, and its biochemical properties were partially characterized. EstL5 was observed to be active within the temperature range of 0-80°C, having maximal activity at 60°C.

Crystal structure of Human ASB9-2 and substrate-recognition of CKB.

Human ankyrin repeat and suppressor of cytokine signaling box protein 9 (hASB9) is a specific substrate-recognition subunit of an elongin C-cullin-SOCS box E3 ubiquitin ligase complex. It recognizes its substrate, brain type creatine kinase (CKB), using the ankyrin repeat domain; and facilitates the polyubiquitination of CKB to mediate proteasomal degradation through the SOCS box domain. HASB9-2 is an isoform of hASB9 that contains one ankyrin repeat domain.

The association of ACT -17 A/T polymorphism with Alzheimer's disease: a meta-analysis.

Association studies between Alpha-1-antichymotrypsin (ACT)-17(A > T) polymorphisms and Alzheimer's disease (AD) susceptibility have shown conflicting results. In this investigation, we performed a meta-analysis to assess the purported associations. Subgroup analyses based on ethnicity (Caucasians, East-Asian and American mixed) were also performed including a total of 5,676 AD patients and 5,460 controls for ACT-17.

A global genomic view on LNX siRNA-mediated cell cycle arrest.

LNX protein is the first described PDZ domain-containing member of the RING finger-type E3 ubiquitin ligase family. Studies have approved that LNX could participate in signal transduction, such as Notch pathway, and play an important role in tumorigenesis. In this study, we found that down-regulation of LNX resulted in G0/G1 cell cycle arrest in G0/G1 phase in HEK293 cells.

Selection of reliable reference genes for gene expression study in nasopharyngeal carcinoma.

Aim: To construct a system for selecting reference genes (RGs) and to select the most optimal RGs for gene expression studies in nasopharyngeal carcinoma (NPC).

Methods: The total RNAs from 20 NPC samples were each labeled with Cy5-dUTP. To create a common control, the total RNA from 15 nasopharyngeal phlogistic (NP) tissues was mixed and labeled via reverse transcription with Cy3-dUTP.

Cellular and molecular mechanisms of photodynamic hypericin therapy for nasopharyngeal carcinoma cells.

Hypericin-mediated photodynamic therapy (HY-PDT) has become a potential treatment for tumors and nonmalignant disorders. Some studies reported that HY-PDT could lead to apoptosis in some carcinoma cells. However, the molecular mechanism of HY-PDT remains unknown.

System biology analysis of cell cycle pathway involved in hepatocellular carcinoma.

To investigate genetic mechanisms of hepatocarcinogenesis and identify potential anticancer targets in hepatocellular carcinoma (HCC), we analyzed microarray gene expression profiles between 33 HCCs and their corresponding noncancerous liver tissues. Functional analysis of differentially-expressed genes in HCC indicated that cell cycle dysregulation plays an important role in hepatocarcinogenesis. Based on 14 differentially-expressed genes involved in cell cycle in HCC, we applied Structural Equation Modeling (SEM) to establish a potential genetic network which could assist understanding of HCC molecular mechanisms.

Expression profile reveals novel prognostic biomarkers in hepatocellular carcinoma.

The purpose of this study was to identify and validate novel prognostic biomarkers in human hepatocellular carcinoma (HCC). We analyzed gene expression profiles not only between 33 HCCs and their corresponding noncancerous liver tissues, but also between 25 HCCs and pooled normal liver tissues using cDNA microarrays containing 12800 genes. Functional analysis of differentially expressed genes involved in HCC carcinogenesis and tumor progression revealed that up-regulated and down-regulated genes are mainly associated with cell cycle and immune response, respectively.

Grb10 interacts with Bim L and inhibits apoptosis.

Bim is a proapoptotic member of the Bcl-2 family and is primarily involved in the regulation of the intrinsic apoptotic pathway. However, the detail of regulation of Bim's proapoptotic activity has not been clarified yet. Using Bim L as bait, we screened a human fetal cDNA library for interacting proteins and identified Grb10 as an interactor.