Microbiota regulates neonatal disease tolerance to virus-evoked necrotizing enterocolitis by shaping the STAT1-NLRC5 axis in the intestinal epithelium.

Microbiota and feeding modes influence the susceptibility of premature newborns to necrotizing enterocolitis (NEC) through mechanisms that remain unknown. Here, we show that microbiota colonization facilitated by breastmilk feeding promotes NOD-like receptor family CARD domain containing 5 (Nlrc5) gene expression in mouse intestinal epithelial cells (IECs). Notably, inducible knockout of the Nlrc5 gene in IECs predisposes neonatal mice to NEC-like injury in the small intestine upon viral inflammation in an NK1.

Enhanced Ionic Polymer-Metal Composites with Nanocomposite Electrodes for Restoring Eyelid Movement of Patients with Ptosis.

The present study aims to use enhanced ionic polymer-metal composites (IPMC) as an artificial muscle (a soft-active actuator) to restore eyelid movement of patients with ptosis. The previous eyelid movement mechanisms contained drawbacks, specifically in the lower eyelid. We used finite element analysis (FEA) to find the optimal mechanism among two different models (A and B).

Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma.

Indoleamine 2,3-dioxygenase 1 (IDO1) is a potent immunosuppressive enzyme that inhibits the antitumor immune response through both tryptophan metabolism and non-enzymatic functions. To date, most IDO1-targeted approaches have focused on inhibiting tryptophan metabolism. However, this class of drugs has failed to improve the overall survival of patients with cancer.

Long-term recovery behavior of brain tissue in hydrocephalus patients after shunting.

The unpredictable complexities in hydrocephalus shunt outcomes may be related to the recovery behavior of brain tissue after shunting. The simulated cerebrospinal fluid (CSF) velocity and intracranial pressure (ICP) over 15 months after shunting were validated by experimental data. The mean strain and creep of the brain had notable changes after shunting and their trends were monotonic.

A New Definition for Intracranial Compliance to Evaluate Adult Hydrocephalus After Shunting.

The clinical application of intracranial compliance (ICC), ∆V/∆P, as one of the most critical indexes for hydrocephalus evaluation was demonstrated previously. We suggest a new definition for the concept of ICC (long-term ICC) where there is a longer amount of elapsed time (up to 18 months after shunting) between the measurement of two values (V and V or P and P). The head images of 15 adult patients with communicating hydrocephalus were provided with nine sets of imaging in nine stages: prior to shunting, and 1, 2, 3, 6, 9, 12, 15, and 18 months after shunting.

Cerebrospinal fluid hydrocephalus shunting: cisterna magna, ventricular frontal, ventricular occipital.

Despite advances in cerebrospinal fluid shunting technology, complications remain a significant concern. There are some contradictions about the effectiveness of proximal catheter entry sites that decrease shunt failures. We aim to compare efficiency of shunts with ventricular frontal, ventricular occipital, and cisterna magna entry sites.

p52 signaling promotes cellular senescence.

Background: Nuclear factor-κB is a multi-subunit transcription factor that plays a central role in cellular senescence. We previously reported that an increase in the p52 subunit is seen in senescent cells and aged tissue. In the current work, we examined the mechanism by which p52 is activated and whether the increase in p52 promotes senescence.

Glioblastoma as an age-related neurological disorder in adults.

Background: Advanced age is a major risk factor for the development of many diseases including those affecting the central nervous system. Wild-type isocitrate dehydrogenase glioblastoma (IDH GBM) is the most common primary malignant brain cancer and accounts for ≥90% of all adult GBM diagnoses. Patients with IDH GBM have a median age of diagnosis at 68-70 years of age, and increasing age is associated with an increasingly worse prognosis for patients with this type of GBM.

Post-Trial Enhanced Deployment and Technical Performance with the MISTIE Procedure per Lessons Learned.

Objective: We hypothesize that procedure deployment rates and technical performance with minimally invasive surgery and thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE) can be enhanced in post-trial clinical practice, per Phase III trial results and lessons learned.

Materials And Methods: We identified ICH patients and those who underwent MISTIE procedure between 2017-2021 at a single site, after completed enrollments in the Phase III trial. Deployment rates, complications and technical outcomes were compared to those observed in the trial.

An Alternative Pipeline for Glioblastoma Therapeutics: A Systematic Review of Drug Repurposing in Glioblastoma.

The treatment of glioblastoma (GBM) remains a significant challenge, with outcome for most pa-tients remaining poor. Although novel therapies have been developed, several obstacles restrict the incentive of drug developers to continue these efforts including the exorbitant cost, high failure rate and relatively small patient population. Repositioning drugs that have well-characterized mechanistic and safety profiles is an attractive alternative for drug development in GBM.

CDK1 is up-regulated by temozolomide in an NF-κB dependent manner in glioblastoma.

The alkylating agent, temozolomide (TMZ), is the most commonly used chemotherapeutic for the treatment of glioblastoma (GBM). The anti-glioma effect of TMZ involves a complex response that includes G2-M cell cycle arrest and cyclin-dependent kinase 1 (CDK1) activation. While CDK1 phosphorylation is a well-described consequence of TMZ treatment, we find that TMZ also robustly induces CDK1 expression.

p50 mono-ubiquitination and interaction with BARD1 regulates cell cycle progression and maintains genome stability.

p50, the mature product of NFKB1, is constitutively produced from its precursor, p105. Here, we identify BARD1 as a p50-interacting factor. p50 directly associates with the BARD1 BRCT domains via a C-terminal phospho-serine motif.

DDX39B interacts with the pattern recognition receptor pathway to inhibit NF-κB and sensitize to alkylating chemotherapy.

Background: Nuclear factor-κB (NF-κB) plays a prominent role in promoting inflammation and resistance to DNA damaging therapy. We searched for proteins that modulate the NF-κB response as a prerequisite to identifying novel factors that affect sensitivity to DNA damaging chemotherapy.

Results: Using streptavidin-agarose pull-down, we identified the DExD/H-box RNA helicase, DDX39B, as a factor that differentially interacts with κB DNA probes.

Regulatable interleukin-12 gene therapy in patients with recurrent high-grade glioma: Results of a phase 1 trial.

Human interleukin-12 (hIL-12) is a cytokine with anticancer activity, but its systemic application is limited by toxic inflammatory responses. We assessed the safety and biological effects of an hIL-12 gene, transcriptionally regulated by an oral activator. A multicenter phase 1 dose-escalation trial (NCT02026271) treated 31 patients undergoing resection of recurrent high-grade glioma.

Temozolomide Treatment Induces lncRNA MALAT1 in an NF-κB and p53 Codependent Manner in Glioblastoma.

Alkylating chemotherapy is a central component of the management of glioblastoma (GBM). Among the factors that regulate the response to alkylation damage, NF-κB acts to both promote and block cytotoxicity. In this study, we used genome-wide expression analysis in U87 GBM to identify NF-κB-dependent factors altered in response to temozolomide and found the long noncoding RNA (lncRNA) MALAT1 as one of the most significantly upregulated.

Primary Sellar Paraganglioma: Case Report with Literature Review and Immunohistochemistry Resource.

Background: Differential diagnosis of sellar masses includes adenoma, meningioma, craniopharyngioma, and metastasis. Primary paraganglioma is seldom considered. We present a case of this unique pathology, review the relevant literature, and compile a compendium of immunohistochemical characteristics for use as a resource.

NF-κB, Mesenchymal Differentiation and Glioblastoma.

Although glioblastoma (GBM) has always been recognized as a heterogeneous tumor, the advent of largescale molecular analysis has enabled robust categorization of this malignancy into several specific subgroups. Among the subtypes designated by expression profiling, mesenchymal tumors have been associated with an inflammatory microenvironment, increased angiogenesis, and resistance to therapy. Nuclear factor-κB (NF-κB) is a ubiquitous transcription factor that plays a prominent role in mediating many of the central features associated with mesenchymal differentiation.

Response to BRAF/MEK Inhibition After Progression With BRAF Inhibition in a Patient With Anaplastic Pleomorphic Xanthoastrocytoma.

Pleomorphic xanthoastrocytoma (PXA) is a rare primary central nervous system tumor which frequently harbors mutations in BRAF. Anaplastic PXA follow a more aggressive course than their nonanaplastic counterparts. We present the case of an anaplastic PXA initially treated with the BRAF inhibitor vemurafenib.

expression promotes resistance to alkylating chemotherapy in gliomas.

The response of patients with gliomas to alkylating chemotherapy is heterogeneous. However, there are currently no universally accepted predictors of patient response to these agents. We identify the nuclear factor κB (NF-κB) co-regulator B cell CLL/lymphoma 3 (BCL-3) as an independent predictor of response to temozolomide (TMZ) treatment.

Convection-Enhanced Delivery of Polymeric Nanoparticles Encapsulating Chemotherapy in Canines with Spontaneous Supratentorial Tumors.

Background: Despite aggressive multimodal treatment, survival for patients with glioblastoma remains dismal. One obstacle to improving patient outcomes is the difficulty in delivering adequate therapeutic to the central nervous system due to the presence of the blood-brain barrier. Although direct drug infusion by convection-enhanced delivery (CED) can bypass the blood-brain barrier and facilitate delivery to intracranial tumors, determining the distribution of delivered therapeutic remains problematic.

Intracranial hemorrhage as initial manifestation of plasma cell myeloma: A case report.

This is the case of a previously healthy 48 year-old male whom presented with mild confusion, low-grade headache, and left sided weakness. Computed tomography of the head revealed a large acute right frontal lobe intracranial hemorrhage (ICH) and intraventricular extension, with normal vascular imaging. Initial laboratory testing was inconsequential.