Impact of Mouthwash-Induced Oral Microbiome Disruption on Alzheimer's Disease Risk: A Perspective Review.

The widespread use of mouthwashes, particularly those containing chlorhexidine (CHX), has raised concerns about their impact on the oral microbiome and potential systemic health effects. This perspective review examines the current evidence linking CHX mouthwash use to disruptions in the oral microbiome and explores the potential indirect implications for Alzheimer's disease (AD) risk. CHX mouthwash is effective in reducing dental plaque and gingival inflammation, but it also significantly alters the composition of the oral microbiome, decreasing the abundance of nitrate-reducing bacteria critical for nitric oxide (NO) production.

Effects of Intermittent Hypoxia Protocols on Cognitive Performance and Brain Health in Older Adults Across Cognitive States: A Systematic Literature Review.

Background: The rise in the aging population highlights the need to address cognitive decline and neurodegenerative diseases. Intermittent hypoxia (IH) protocols show promise in enhancing cognitive abilities and brain health.

Objective: This review evaluates IH protocols' benefits on cognition and brain health in older adults, regardless of cognitive status.

Unconventional activation of PRKDC by TNF-α: deciphering its crucial role in Th1-mediated inflammation beyond DNA repair as part of the DNA-PK complex.

Background: The DNA-dependent protein kinase (DNA-PK) complex comprises a catalytic (PRKDC) and two requisite DNA-binding (Ku70/Ku80) subunits. The role of the complex in repairing double-stranded DNA breaks (DSBs) is established, but its role in inflammation, as a complex or individual subunits, remains elusive. While only ~ 1% of PRKDC is necessary for DNA repair, we reported that partial inhibition blocks asthma in mice without causing SCID.

Could the Historical Transition from Segmented to Monophasic Sleep Explain the Modern Insurgence of Alzheimer's Disease and Related Dementias?

 In their article, Finch and Burstein explore the hypothesis that Alzheimer's disease and related dementias (ADRD) may predominantly be phenomena of the modern era. Through a review of classical Greek and Latin literature, they found minimal reference to conditions akin to ADRD, suggesting a historical rarity of severe cognitive decline. Instead, ancient texts focused on physical aspects of aging, with cognitive changes, when noted, not resembling modern-day dementia.

Effects of a Physical Activity Program that Incorporates Exercises Targeting Balance, Strength, and Proprioception on Cognitive Functions and Physical Performance in Old Adults with Mild Cognitive Impairment.

Background: Aging often leads to cognitive function decline, sensory structure deterioration, and musculoskeletal system weakening. This impacts postural control during static and dynamic activities like walking, increasing the fall risk among the elderly. Older adults with mild cognitive impairment (MCI) face an elevated fall risk and cognitive decline, magnifying the public health concern.

Differential effects of poly(ADP ribose) polymerase inhibitor-based metronomic therapy on programmed death-ligand 1 and matrix-associated factors in human myeloid cells.

We recently showed that while partial poly(ADP-ribose) polymerase (PARP)-1 inhibition with a low metronomic sub-half-maximal inhibitory concentration/dose (IC50) of olaparib provides superior protection against colon cancer in mice compared to complete inhibition by blocking the suppressive function of myeloid-derived suppressor cells (MDSCs) and synergizing with anti-program cell death (PD)-1-based immunotherapy. Here, we examined whether PARP inhibitors (PARPi) exert effects on human myeloid cells that alter T cell function (e.g.

Promotion of a synthetic degradation of activated STAT6 by PARP-1 inhibition: roles of poly(ADP-ribosyl)ation, calpains and autophagy.

Background: We reported that PARP-1 regulates genes whose products are crucial for asthma, in part, by controlling STAT6 integrity speculatively through a calpain-dependent mechanism. We wished to decipher the PARP-1/STAT6 relationship in the context of intracellular trafficking and promoter occupancy of the transcription factor on target genes, its integrity in the presence of calpains, and its connection to autophagy.

Methods: This study was conducted using primary splenocytes or fibroblasts derived from wild-type or PARP-1 mice and Jurkat T cells to mimic Th2 inflammation.

Targeting the Cbl-b-Notch1 axis as a novel immunotherapeutic strategy to boost CD8+ T-cell responses.

A critical feature of cancer is the ability to induce immunosuppression and evade immune responses. Tumor-induced immunosuppression diminishes the effectiveness of endogenous immune responses and decreases the efficacy of cancer immunotherapy. In this study, we describe a new immunosuppressive pathway in which adenosine promotes Casitas B-lineage lymphoma b (Cbl-b)-mediated Notch1 degradation, causing suppression of CD8+ T-cells effector functions.

Swimming and the human microbiome at the intersection of sports, clinical, and environmental sciences: A scoping review of the literature.

The human microbiota is comprised of more than 10-100 trillion microbial and symbiotic cells. Two major human sites that are host to microbial communities are the gut and the skin. Physical exercise has favorable effects on the structure of human microbiota and metabolite production in sedentary subjects.

Nuclear interaction of Arp2/3 complex and BRAF promotes aggressive behavior and vemurafenib resistance of thyroid cancer.

The presence of mutant BRAF correlates with the risk of recurrence in papillary thyroid cancer (PTC) patients. However, not all PTC patients with BRAF are associated with poor prognosis. Thus, understanding the mechanisms by which certain PTC patients with nuclear BRAF become aggressive and develop resistance to a selective BRAF inhibitor, PLX-4032, is urgently needed.

Combination of Tipifarnib and Sunitinib Overcomes Renal Cell Carcinoma Resistance to Tyrosine Kinase Inhibitors via Tumor-Derived Exosome and T Cell Modulation.

Background: Tyrosine kinase inhibitors (TKI) were initially demonstrated as an efficacious treatment for renal cell carcinoma (RCC). However, after a median treatment length of 14 months, a vast majority of patients develop resistance. This study analyzed a combination therapy of tipifarnib (Tipi) + sunitinib that targeted exosome-conferred drug resistance.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study.

Background And Objective: We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).

Methods: Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.

Targeting PARP-1 with metronomic therapy modulates MDSC suppressive function and enhances anti-PD-1 immunotherapy in colon cancer.

Background: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored.

Methods: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression.

PARP-1 Is Critical for Recruitment of Dendritic Cells to the Lung in a Mouse Model of Asthma but Dispensable for Their Differentiation and Function.

Dendritic cells (DCs) are critical in asthma and many other immune diseases. We previously demonstrated a role for PARP-1 in asthma. Evidence on PARP-1 playing a role in Th2-associated DC function is not clear.

Microparticles in systemic sclerosis: Potential pro-inflammatory mediators and pulmonary hypertension biomarkers.

Background And Objective: Endothelial microparticles (EMP) are submicron vesicles released from endothelial cells. We aimed to determine the utility of EMP as biomarkers of pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients and the pathogenic role of microparticles (MP) in vascular inflammation.

Methods: Levels of EMP (CD144+, CD31+, CD62E+ and CD143+) were compared between three groups (10 SSc patients with PAH, 10 SSc patients without pulmonary hypertension (no-PH) and 10 healthy age- and sex-matched controls).

Sulfated non-anticoagulant heparin blocks Th2-induced asthma by modulating the IL-4/signal transducer and activator of transcription 6/Janus kinase 1 pathway.

Background: The efficacy of heparins and low-MW-heparins (LMWH) against human asthma has been known for decades. However, the clinical utility of these compounds has been hampered by their anticoagulant properties. Much effort has been put into harnessing the anti-inflammatory properties of LMWH but none have been used as therapy for asthma.

Bortezomib sensitizes thyroid cancer to BRAF inhibitor and .

Although overall survival rate for patients with thyroid cancer (TC) is high, there is an alarming 10-year recurrence rate of up to 30% conferring a ~50% survival among these high-risk patients. The BRAF mutation is estimated to be present in over 50% of papillary thyroid cancer (PTC) cases besides being associated with carcinogenesis and poor prognosis. We assessed the status of NF-κB, Ki-67, cyclin D1 and BRAF in TC tissues and TC cell lines using immunohistochemistry and Western blot analysis.

Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

Background: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology.

Opportunities for the repurposing of PARP inhibitors for the therapy of non-oncological diseases.

Unlabelled: The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury.

PARP inhibition protects against alcoholic and non-alcoholic steatohepatitis.

Background & Aims: Mitochondrial dysfunction, oxidative stress, inflammation, and metabolic reprograming are crucial contributors to hepatic injury and subsequent liver fibrosis. Poly(ADP-ribose) polymerases (PARP) and their interactions with sirtuins play an important role in regulating intermediary metabolism in this process. However, there is little research into whether PARP inhibition affects alcoholic and non-alcoholic steatohepatitis (ASH/NASH).

Immunohistochemistry as an accurate tool for evaluating BRAF-V600E mutation in 130 samples of papillary thyroid cancer.

Background: BRAF mutation has been investigated by immunohistochemistry and has shown high sensitivity and specificity. We aim to investigate the accuracy of immunohistochemistry versus molecular testing of BRAF in papillary thyroid cancer using a large number of polymerase chain reaction-positive BRAF papillary thyroid cancer tissues.

Methods: We stained 130 formalin-fixed papillary thyroid cancer specimens using the VE1 antibody: 100 BRAF positive and 30 BRAF negative confirmed by PCR.

Potential of Inducible Nitric Oxide Synthase as a Therapeutic Target for Allergen-Induced Airway Hyperresponsiveness: A Critical Connection to Nitric Oxide Levels and PARP Activity.

Although expression of inducible NO synthase (iNOS) in the lungs of asthmatics and associated nitrosative damage are established, iNOS failed as a therapeutic target for blocking airway hyperresponsiveness (AHR) and inflammation in asthmatics. This dichotomy calls for better strategies with which the enzyme is adequately targeted. Here, we confirm iNOS expression in the asthmatic lung with concomitant protein nitration and poly(ADP-ribose) polymerase (PARP) activation.