RBC-derived vesicles as a systemic delivery system of doxorubicin for lysosomal-mitochondrial axis-improved cancer therapy.

Introduction: Chemotherapeutic drugs are the main intervention for cancer management, but many drawbacks impede their clinical applications. Nanoparticles as drug delivery systems (DDSs) offer much promise to solve these limitations.

Objectives: A novel nanocarrier composed of red blood cell (RBC)-derived vesicles (RDVs) surface-linked with doxorubicin (Dox) using glutaraldehyde (glu) to form Dox-gluRDVs was investigated for improved cancer therapy.

Dipeptidyl peptidase 9 sets a threshold for CARD8 inflammasome formation by sequestering its active C-terminal fragment.

CARD8 detects intracellular danger signals and forms a caspase-1 activating inflammasome. Like the related inflammasome sensor NLRP1, CARD8 autoprocesses into noncovalently associated N-terminal (NT) and C-terminal (CT) fragments and binds the cellular dipeptidyl peptidases DPP8 and 9 (DPP8/9). Certain danger-associated signals, including the DPP8/9 inhibitor Val-boroPro (VbP) and HIV protease, induce proteasome-mediated NT degradation and thereby liberate the inflammasome-forming CT.

Nucleic Acid-Based Therapeutics in Orphan Neurological Disorders: Recent Developments.

The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid-based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood-brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support.

Endonasal CNS Delivery System for Blood-Brain Barrier Impermeant Therapeutic Oligonucleotides Using Heterotopic Mucosal Engrafting.

The most significant obstacle in the treatment of neurological disorders is the blood-brain barrier (BBB), which prevents 98% of all potential neuropharmaceuticals from reaching the central nervous system (CNS). Brain derived neurotrophic factor (BDNF) is one of the most intensely studied targets in Parkinson's disease (PD) as it can reverse disease progression. BDNF AntagoNAT's (ATs) are synthetic oligonucleotide-like compounds capable of upregulating endogenous BDNF expression.

Investigating the association between serum human papillomavirus type 16 E7 antibodies and risk of head and neck cancer.

Human papillomavirus (HPV) is recognized as a major cause of oropharyngeal cancer (OPC) in Western countries. Less is known regarding its contribution to the OPC occurring in Asia. The current study aimed to investigate the association between antibody responses to HPV16 E7 and head and neck cancer (HNC) risk in a hospital-based case-control study conducted in Taiwan with 693 HNC cases and 1,035 controls.

Eye movement analysis with hidden Markov models (EMHMM) with co-clustering.

The eye movement analysis with hidden Markov models (EMHMM) method provides quantitative measures of individual differences in eye-movement pattern. However, it is limited to tasks where stimuli have the same feature layout (e.g.

Powerful Q-switched Raman laser at 589 nm with a repetition rate between 200 and 500 kHz.

We demonstrate a highly powerful acousto-optically -switched : yellow laser at 589 nm by using a -cut KGW crystal and a phase-matching lithium triborate crystal to performance the intracavity stimulated Raman scattering and second-harmonic generation, respectively. We experimentally verify that the design of the separate cavity is superior to the conventional design of the shared cavity. By using the separate cavity, the optical-to-optical efficiency can be generally higher than 32% for the repetition rate within 200-500 kHz.

Characterizing perimenstrual flares of hidradenitis suppurativa.

Background: Hidradenitis suppurativa (HS) predominantly affects women of childbearing age, and sex hormones are thought to play a role in HS pathogenesis. However, there is a paucity of data regarding the pattern of HS perimenstrual flares, as well as patient responses to hormone-based therapies.

Objective: We aimed to characterize the temporal pattern of perimenstrual flares, as well as factors associated with perimenstrual flares.

Menses, pregnancy, delivery, and menopause in hidradenitis suppurativa: A patient survey.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disorder that primarily affects women of childbearing age. There is a paucity of data on HS disease activity during menstruation, pregnancy, and menopause and the potential impact of HS on the method of delivery.

Objective: We aimed to characterize the natural history of HS symptoms during menses, pregnancy, and menopause.

c-MYC-directed NRF2 drives malignant progression of head and neck cancer via glucose-6-phosphate dehydrogenase and transketolase activation.

NRF2, a redox sensitive transcription factor, is up-regulated in head and neck squamous cell carcinoma (HNSCC), however, the associated impact and regulatory mechanisms remain unclear. The protein expression of NRF2 in HNSCC specimens was examined by IHC. The regulatory effect of c-MYC on NRF2 was validated by ChIP-qPCR, RT-qPCR and western blot.

Reduced MC4R signaling alters nociceptive thresholds associated with red hair.

Humans and mice with natural red hair have elevated basal pain thresholds and an increased sensitivity to opioid analgesics. We investigated the mechanisms responsible for higher nociceptive thresholds in red-haired mice resulting from a loss of melanocortin 1 receptor (MC1R) function and found that the increased thresholds are melanocyte dependent but melanin independent. MC1R loss of function decreases melanocytic proopiomelanocortin transcription and systemic melanocyte-stimulating hormone (MSH) levels in the plasma of red-haired ( ) mice.

Insulin-like growth factor binding protein 3 promotes radiosensitivity of oral squamous cell carcinoma cells via positive feedback on NF-κB/IL-6/ROS signaling.

Background: Ectopic insulin-like growth factor binding protein 3 (IGFBP3) expression has been shown to enhance cell migration and lymph node metastasis of oral squamous cell carcinoma (OSCC) cells. However, OSCC patients with high IGFBP3 expression had improved survival compared with those with low expression. Therefore, we speculated that IGFBP3 expression may play a role in response to conventional OSCC therapies, such as radiotherapy.

Clinical Epidemiology and Management of Hidradenitis Suppurativa.

Hidradenitis suppurativa is a chronic immune-mediated inflammatory skin disease with a prevalence of 0.1-1%, characterized by nodules and abscesses in the axillae, groin, and inframammary areas, sometimes developing into tunnels (or fistulas) and scars. Because hidradenitis suppurativa is more common in women and in those aged 18-40 years, obstetrician-gynecologists (ob-gyns) have the opportunity to diagnose, educate, initiate treatment, and coordinate care with ancillary health care professionals.

Tuning DNA-nanoparticle conjugate properties allows modulation of nuclease activity.

Enzyme-nanoparticle interactions can give rise to a range of new phenomena, most notably significant enzymatic rate enhancement. Accordingly, the careful study and optimization of such systems is likely to give rise to advanced biosensing applications. Herein, we report a systematic study of the interactions between nuclease enzymes and oligonucleotide-coated gold nanoparticles (spherical nucleic acids, SNAs), with the aim of revealing phenomena worthy of evolution into functional nanosystems.

Do portrait artists have enhanced face processing abilities? Evidence from hidden Markov modeling of eye movements.

Recent research has suggested the importance of part-based information in face recognition in addition to global, whole-face information. Nevertheless, face drawing experience was reported to enhance selective attention to the eyes but did not improve face recognition performance, leading to speculations about limited plasticity in adult face recognition. Here we examined the mechanism underlying the limited advantage of face drawing experience in face recognition through the Eye Movement analysis with Hidden Markov Models (EMHMM) approach.

Medicaid and Medicare Part B spending on immunomodulators and biosimilars.

Introduction: Prices for immunomodulators used in dermatological conditions are rising in the United States. While Medicare Part-D solely covers medication costs, Medicare Part-B covers outpatient infusion and injection costs given by medical professionals. We aim to analyze recent trends in Medicare Part-B spending on immunomodulators and their biosimilars used in the treatment of common chronic inflammatory dermatoses.

Construction of intracellular asymmetry and asymmetric division in Escherichia coli.

The design principle of establishing an intracellular protein gradient for asymmetric cell division is a long-standing fundamental question. While the major molecular players and their interactions have been elucidated via genetic approaches, the diversity and redundancy of natural systems complicate the extraction of critical underlying features. Here, we take a synthetic cell biology approach to construct intracellular asymmetry and asymmetric division in Escherichia coli, in which division is normally symmetric.