Complete, Durable Remission of Advanced Hepatocellular Carcinoma under Treatment with Viscum album Extracts: A Case Report.

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths. Early-stage disease is treated with curative intent, but most patients present with advanced HCC, which carries a poor prognosis. Viscum album extracts (VAE) are used by cancer patients as an adjunct treatment or palliation.

Reprogramming reactive glia into interneurons reduces chronic seizure activity in a mouse model of mesial temporal lobe epilepsy.

Reprogramming brain-resident glial cells into clinically relevant induced neurons (iNs) is an emerging strategy toward replacing lost neurons and restoring lost brain functions. A fundamental question is now whether iNs can promote functional recovery in pathological contexts. We addressed this question in the context of therapy-resistant mesial temporal lobe epilepsy (MTLE), which is associated with hippocampal seizures and degeneration of hippocampal GABAergic interneurons.

Neuronal tau species transfer to astrocytes and induce their loss according to tau aggregation state.

Deposits of different abnormal forms of tau in neurons and astrocytes represent key anatomo-pathological features of tauopathies. Although tau protein is highly enriched in neurons and poorly expressed by astrocytes, the origin of astrocytic tau is still elusive. Here, we used innovative gene transfer tools to model tauopathies in adult mouse brains and to investigate the origin of astrocytic tau.

Chronic Kidney Disease in Patients Undergoing Cardiac Device Placement: Results of a Retrospective Study.

Background: Cardiovascular issues (especially arrhythmia and sudden cardiac death) are one of the most common causes of mortality in patients with chronic kidney disease (CKD). To minimize cardiac mortality, these patients frequently require various cardiac devices, such as pacemakers, loop recorders, and defibrillators which can compromise their vascular access. In this study, we aim to determine the prevalence of CKD in patients undergoing cardiac device placement and their progression of CKD.

Amyloid Beta and Tau Cooperate to Cause Reversible Behavioral and Transcriptional Deficits in a Model of Alzheimer's Disease.

A key knowledge gap blocking development of effective therapeutics for Alzheimer's disease (AD) is the lack of understanding of how amyloid beta (Aβ) peptide and pathological forms of the tau protein cooperate in causing disease phenotypes. Within a mouse tau-deficient background, we probed the molecular, cellular, and behavioral disruption triggered by the influence of wild-type human tau on human Aβ-induced pathology. We find that Aβ and tau work cooperatively to cause a hyperactivity behavioral phenotype and to cause downregulation of transcription of genes involved in synaptic function.

Direct Lineage Reprogramming for Brain Repair: Breakthroughs and Challenges.

Injury to the human central nervous system (CNS) is devastating because our adult mammalian brain lacks intrinsic regenerative capacity to replace lost neurons and induce functional recovery. An emerging approach towards brain repair is to instruct fate conversion of brain-resident non-neuronal cells into induced neurons (iNs) by direct lineage reprogramming. Considerable progress has been made in converting various source cell types of mouse and human origin into clinically relevant iNs.

By Activating Akt/eNOS Bilobalide B Inhibits Autophagy and Promotes Angiogenesis Following Focal Cerebral Ischemia Reperfusion.

Background/aims: Ischemic stroke is a leading cause of long-term disability. To date, there is no effective treatment for stroke. Previous studies have shown that Ginkgo biloba extract has protective effects against neurodegenerative disorders.

Potentiating tangle formation reduces acute toxicity of soluble tau species in the rat.

Tauopathies are neurodegenerative diseases characterized by the aggregation of tau protein. These pathologies exhibit a wide variety of clinical and anatomo-pathological presentations, which may result from different pathological mechanisms. Although tau inclusions are a common feature in all these diseases, recent evidence instead implicates small oligomeric aggregates as drivers of tau-induced toxicity.

UCH-L1 promotes invasion of breast cancer cells through activating Akt signaling pathway.

As a de-ubiquitin enzyme, ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to be overexpressed in several human cancers. However, the function of UCH-L1 in invasion of breast cancers is still unclear. Here we report that the expression of UCH-L1 is significantly higher in cancer cells with higher invasive ability.

Coley's Lessons Remembered: Augmenting Mistletoe Therapy.

The following four observations point in the same direction, namely that there is an unleveraged potential for stimulating the innate immune system against cancer: (1) experimental treatments with bacterial extracts more than 100 years ago by Coley and contemporaries, (2) a positive correlation between spontaneous regressions and febrile infection, (3) epidemiological data suggesting an inverse correlation between a history of infection and the likelihood of developing cancer, and (4) our recent finding that a cocktail of pattern recognition receptor ligands (PRRLs) can eradicate solid tumors in cancer mice if applied metronomically. Because the main immunostimulating component of mistletoe extract (ME), mistletoe lectin, has been shown to be a PRRL as well, we suggest to apply ME in combination with additional PRRLs. Additional PRRLs can be found in approved drugs already on the market.

PTRF suppresses the progression of colorectal cancers.

As a key component of caveolae structure on the plasma membrane, accumulated evidence has suggested that Polymerase I and Transcript Release Factor (PTRF) plays a pivotal role in suppressing the progression of human malignances. However, the function of PTRF in the development of colorectal cancers is still unclear. Here we report that the expression of PTRF is significantly reduced in tumor tissues derived from human patients with colorectal cancers, and that the downregulation of PTRF correlates to the advanced stage of the disease.

Modulation of wound healing and scar formation by MG53 protein-mediated cell membrane repair.

Cell membrane repair is an important aspect of physiology, and disruption of this process can result in pathophysiology in a number of different tissues, including wound healing, chronic ulcer and scarring. We have previously identified a novel tripartite motif family protein, MG53, as an essential component of the cell membrane repair machinery. Here we report the functional role of MG53 in the modulation of wound healing and scarring.

EUS-Guided FNA for Diagnosis of Pancreatic Cystic Lesions: a Meta-Analysis.

Background: Preoperative diagnosis of pancreatic cystic lesions (PCLs) must be reliable as the current standard treatment, major or total pancreatectomy, dramatically affects quality of life. Additionally, early diagnosis of malignancy is essential to an improved prognosis. The diagnostic accuracy of fluid analysis using endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has been demonstrated in pancreatic solid lesions.

Evidence that the presynaptic vesicle protein CSPalpha is a key player in synaptic degeneration and protection in Alzheimer's disease.

Background: In Alzheimer's disease synapse loss precedes neuronal loss and correlates best with impaired memory formation. However, the mechanisms underlying synaptic degeneration in Alzheimer's disease are not well known. Further, it is unclear why synapses in AD cerebellum are protected from degeneration.

Durable Regression of Primary Cutaneous B-Cell Lymphoma Following Fever-inducing Mistletoe Treatment: Two Case Reports.

Background: Mistletoe is a complementary cancer treatment that is widely used, usually in addition to and alongside recommended conventional cancer therapy. However, little is known about its use, effectiveness, and safety in the treatment of cutaneous lymphoma.

Case Report: Two patients with primary cutaneous B-cell lymphoma (pT2bcNxM0 follicle center and pT2ac-NxM0 marginal zone) either declined or postponed recommended conventional treatment and received high-dose, fever-inducing mistletoe treatment; a combination of intratumoral, subcutaneous, and intravenous application was given; and one patient also underwent whole-body hyperthermia.

Store-operated calcium entry is present in HL-1 cardiomyocytes and contributes to resting calcium.

Store-operated Ca(2+) entry (SOCE) has recently been shown to be of physiological and pathological importance in the heart, particularly during cardiac hypertrophy. However, measuring changes in intracellular Ca(2+) during SOCE is very difficult to study in adult primary cardiomyocytes. As a result there is a need for a stable and reliable in vitro model of SOCE which can be used to test cardiac drugs and investigate the role of SOCE in cardiac pathology.

Visualization of MG53-mediated cell membrane repair using in vivo and in vitro systems.

Repair of acute injury to the cell membrane is an elemental process of normal cellular physiology, and defective membrane repair has been linked to many degenerative human diseases. The recent discovery of MG53 as a key component of the membrane resealing machinery allows for a better molecular understanding of the basic biology of tissue repair, as well as for potential translational applications in regenerative medicine. Here we detail the experimental protocols for exploring the in vivo function of MG53 in repair of muscle injury using treadmill exercise protocols on mouse models, for testing the ex vivo membrane repair capacity by measuring dye entry into isolated muscle fibers, and for monitoring the dynamic process of MG53-mediated vesicle trafficking and cell membrane repair in cultured cells using live cell confocal microscopy.