Acute physical exercise and ambulatory blood pressure in resistant hypertension.

Objectives: The effects of acute physical exercise in patients with resistant hypertension remain largely unexplored compared with hypertensive patients in general. We assessed the short-term effects of acute moderate-intensity (MICE) and high-intensity interval exercise (HIIE) on the clinic (BP) and 24-h ambulatory blood pressure (ABP) of patients with resistant hypertension.

Methods: Using a crossover randomized controlled design, 10 participants (56 ± 7 years) with resistant hypertension performed three experimental sessions: MICE, HIIE, and control.

Computational Insights into Membrane Disruption by Cell-Penetrating Peptides.

Cell-penetrating peptides (CPPs) can translocate into cells without inducing cytotoxicity. The internalization process implies several steps at different time scales ranging from microseconds to minutes. We combine adaptive Steered Molecular Dynamics (aSMD) with conventional Molecular Dynamics (cMD) to observe nonequilibrium and equilibrium states to study the early mechanisms of peptide-bilayer interaction leading to CPPs internalization.

N-glycosylation in the SERPIN domain of C1-Esterase Inhibitor in hereditary angioedema.

Hereditary angioedema is an autosomal dominant disorder caused by defects in C1-esterase inhibitor (C1-INH), resulting in poorly controlled activation of the kallikrein-kinin system and bradykinin overproduction. C1-INH is a heavily glycosylated protein in the serine protease inhibitor (SERPIN) family, yet the role of these glycosylation sites remains unclear. To elucidate the functional impact of N-glycosylation in the SERPIN domain of C1-INH, we engineered four sets consisting of 26 variants at or near the N-linked sequon (NXS/T).

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Extracellular vesicles: from intracellular trafficking molecules to fully fortified delivery vehicles for cancer therapeutics.

Extracellular vesicles (EVs) are emerging as viable tools in cancer treatment due to their ability to carry a wide range of theranostic activities. This review summarizes different forms of EVs such as exosomes, microvesicles, apoptotic bodies, and oncosomes. It also sheds the light onto isolation methodologies, characterization techniques and therapeutic applications of all discussed EVs.

Exploring the anti-aging potential of natural products and plant extracts in budding yeast : A review.

Historically, plant derived natural products and their crude extracts have been used to treat a wide range of ailments across the world. Biogerontology research aims to explore the molecular basis of aging and discover new anti-aging therapeutic compounds or formulations to combat the detrimental effects of aging and promote a healthy life span. The budding yeast has been, and continues to be, an indispensable model organism in the field of biomedical research for discovering the molecular basis of aging has preserved nutritional signaling pathways (such as the target of rapamycin (TOR)-Sch9 and the Ras-AC-PKA (cAMP-dependent protein kinase) pathways, and shows two distinct aging paradigms chronological life span (CLS) and replicative life span (RLS).

Toward alpha-synuclein seed amplification assay in clinical practice.

Introduction: Seed amplification assays (SAAs) demonstrate remarkable diagnostic performance in alpha-synucleinopathies. However, existing protocols lack accessibility in routine laboratories, mainly due to the requirement for in-house production of recombinant alpha-synuclein (aSyn). This study proposes a cerebrospinal fluid (CSF) aSyn-SAA protocol using solely commercial reagents to facilitate its clinical implementation.

Cyto-Genotoxic Assessment of Sulfoxaflor in Allium cepa Root Cells and DNA Docking Studies.

Sulfoxaflor (SFX) is an insecticide that is commonly used for the control of sap-feeding insects. Since SFX is extensively applied globally, it has been implicated in the substantial induction of environmental toxicity. Therefore, in this study, Allium cepa roots have been employed to elucidate the potential cytogenotoxic effects of SFX in non-target cells by examination of mitotic index (MI), chromosomal aberrations (CAs), and DNA damage.

Halophyte-based crop managements induce biochemical, metabolomic and proteomic changes in tomato plants under saline conditions.

Halophytes display distinctive physiological mechanisms that enable their survival and growth under extreme saline conditions. This makes them potential candidates for their use in saline agriculture. In this research, tomato (Solanum lycopersium Mill.

Multi-Targeting Macrocyclic Peptides as Nanomolar Inhibitors of Self- and Cross-Seeded Amyloid Self-Assembly of α-Synuclein.

Amyloid self-assembly of α-synuclein (αSyn) is linked to the pathogenesis of Parkinson's disease (PD). Type 2 diabetes (T2D) has recently emerged as a risk factor for PD. Cross-interactions between their amyloidogenic proteins may act as molecular links.

Application of Chinese Medicine in Treatment of Ulcerative Colitis and Elucidation of Relevant Mechanisms.

Ulcerative colitis (UC) is a chronic, non-specific intestinal disease of unknown etiology, with high incidence rates worldwide. At present, Western medicine treatments have been associated with more adverse effects and poor efficacy. Chinese medicine (CM) is commonly used as an adjuvant treatment for the unique advantages in regulating immune function, repairing intestinal mucosa, and alleviating intestinal inflammation.

Boric acid impedes glioblastoma growth in a rat model: insights from multi-approach analysis.

Limited advancements in managing malignant brain tumors have resulted in poor prognoses for glioblastoma (GBM) patients. Standard treatment involves surgery, radiotherapy, and chemotherapy, which lack specificity and damage healthy brain tissue. Boron-containing compounds, such as boric acid (BA), exhibit diverse biological effects, including anticancer properties.

A comparative study of human amniotic membrane, tilapia skin collagen, and Centella asiatica derived gel to treat burn wound in rat model.

In the quest for an ideal wound healing material, human amniotic membrane (AM), tilapia skin collagen (TSC), and Centella asiatica (CA) have been studied separately for their healing potential. In this study, we formulated AM, TSC, and CA gel and studied their competency and wound healing efficacy in vivo. Gel was formulated using AM, TSC, CA, Carbopol 934, acrylic acid, glycerine, and triethanolamine and physicochemical properties e.

Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis.

Adipogenesis is the healthy expansion of white adipose tissue (WAT), serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the body. Therefore, the identification of novel regulatory molecules in adipogenesis, specifically membrane receptors such as G protein-coupled receptors (GPCRs), holds significant clinical promise. These receptors can serve as viable targets for pharmaceuticals, offering potential for restoring metabolic homeostasis in individuals with obesity.

Aβ42 biomarker linked to insula, striatum, thalamus and claustrum in dementia with Lewy bodies.

The differential mechanisms between proteinopathies and neurodegeneration in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remain unclear. To address this issue, we conducted a voxel-based morphometry and cerebrospinal fluid biomarker (α-synuclein, Aβ42, t-Tau and p-Tau) level correlation study in patients with DLB, AD and mixed cases (AD + DLB). Cerebrospinal fluid samples obtained by lumbar puncture and whole-brain T1-weighted images were collected in the AlphaLewyMA cohort.

Therapeutic potential of stromal vascular fraction in early diabetic nephrotoxicity: a histomorphometric and immunohistochemical analysis in type 2 diabetes rat model.

Background: Diabetic nephropathy (DN), a common complication of type 2 diabetes (T2D), significantly contributes to end-stage kidney disease (ESKD). Despite conventional treatments aimed at slowing disease progression, there is a pressing need for novel therapies. This study evaluates the potential therapeutic impact of adipose tissue derived stromal vascular fraction (SVF) on early diabetic nephrotoxicity in a rat model.

Comparing the Effect of Heat Therapy and Mitochondrial-Targeted Antioxidants in Polycystic Ovarian Syndrome Phenotype Induced by Junk Food Consumption.

Polycystic ovarian syndrome (PCOS) is a complex endocrine-metabolic disorder, and multiple factors contribute to its pathophysiology. The current study assessed a PCOS-like animal model induced by consuming a high-fat sugar (HFHS) diet and compared the treatment outcome of mitochondrial-targeted antioxidants versus heat therapy. Sixty rats were divided into the following study groups: three control groups (negative and positive for the treatments used), HFHS, hot tub therapy (HTT) treatment, and MitoQ10 treatment (500 µmol/L MitoQ10 in clean drinking water daily, from week fourteen till week twenty-two of the study).

Phosphoproteomics for studying signaling pathways evoked by hormones of the renin-angiotensin system: A source of untapped potential.

The Renin-Angiotensin System (RAS) is a complex neuroendocrine system consisting of a single precursor protein, angiotensinogen (AGT), which is processed into various peptide hormones, including the angiotensins [Ang I, Ang II, Ang III, Ang IV, Ang-(1-9), Ang-(1-7), Ang-(1-5), etc] and Alamandine-related peptides [Ang A, Alamandine, Ala-(1-5)], through intricate enzymatic pathways. Functionally, the RAS is divided into two axes with opposing effects: the classical axis, primarily consisting of Ang II acting through the AT receptor (ATR), and in contrast the protective axis, which includes the receptors Mas, ATR and MrgD and their respective ligands. A key area of RAS research is to gain a better understanding how signaling cascades elicited by these receptors lead to either "classical" or "protective" effects, as imbalances between the two axes can contribute to disease.

Concurrent RB1 and P53 pathway disruption predisposes to the development of a primitive neuronal component in high-grade gliomas depending on MYC-driven EBF3 transcription.

The foremost feature of glioblastoma (GBM), the most frequent malignant brain tumours in adults, is a remarkable degree of intra- and inter-tumour heterogeneity reflecting the coexistence within the tumour bulk of different cell populations displaying distinctive genetic and transcriptomic profiles. GBM with primitive neuronal component (PNC), recently identified by DNA methylation-based classification as a peculiar GBM subtype (GBM-PNC), is a poorly recognized and aggressive GBM variant characterised by nodules containing cells with primitive neuronal differentiation along with conventional GBM areas. In addition, the presence of a PNC component has been also reported in IDH-mutant high-grade gliomas (HGGs), and to a lesser extent to other HGGs, suggesting that regardless from being IDH-mutant or IDH-wildtype, peculiar genetic and/or epigenetic events may contribute to the phenotypic skewing with the emergence of the PNC phenotype.

Creating a Halotolerant Degrader for Efficient Mineralization of p-Nitrophenol-Substituted Organophosphorus Pesticides in High-Saline Wastewater.

The bioaugmentation performance is severely reduced in the treatment of high-saline pesticide wastewater because the growth and degradation activity of pesticide degraders are significantly inhibited by high salt concentrations. In this study, a heterologous biodegradation pathway comprising the seven genes mpd/pnpABCDEF responsible for the bioconversion of p-nitrophenol (PNP)-substituted organophosphorus pesticides (OPs) into β-oxoadipate and the genes encoding Vitreoscilla hemoglobin (VHb) and green fluorescent protein (GFP) were integrated into the genome of a salt-tolerant chassis Halomonas cupida J9, to generate a genetically engineered halotolerant degrader J9U-MP. RT-PCR assays demonstrated that the nine exogenous genes are successfully transcribed to mRNA in J9U-MP.

A Novel Statistical Method for Unmasking Sex-Specific Genomics Signatures in Complex Traits.

Genotype-phenotype association studies have advanced our understanding of complex traits but often overlook sex-specific genetic signals. The growing awareness of sex-specific influences on human traits and diseases necessitates tailored statistical methodologies to dissect these genetic intricacies. Rare genetic variants play a significant role in disease development, often exhibiting stronger per-allele effects than common variants.

Role of long non-coding RNAs and natural products in prostate cancer: insights into key signaling pathways.

Prostate cancer (PC) ranks among the most prevalent cancers in males. Recent studies have highlighted intricate connections between long non-coding RNAs (lncRNAs), natural products, and cellular signaling in PC development. LncRNAs, which are RNA transcripts without protein-coding function, influence cell growth, programmed cell death, metastasis, and resistance to treatments through pathways like PI3K/AKT, WNT/β-catenin, and androgen receptor signaling.

Specific sets of geranylgeranyl diphosphate synthases and phytoene synthases control the production of carotenoids and ABA in different tomato tissues.

Plant carotenoids are plastid-synthesized isoprenoids with roles as photoprotectants, pigments, and precursors of bioactive molecules such as the hormone abscisic acid (ABA). The first step of the carotenoid biosynthesis pathway is the production of phytoene from geranylgeranyl diphosphate (GGPP), catalyzed by phytoene synthase (PSY). GGPP produced by plastidial GGPP synthases (GGPPS) is channeled to the carotenoid pathway by direct interaction of GGPPS and PSY enzymes.

Human gut microbiota-fermented asparagus powder protects human epithelial cells from injury and inflammation.

Dietary consumption of green asparagus has been associated with several health benefits. These beneficial properties are attributed to the presence of many bioactive compounds in asparagus, including saponins, phenolics, flavonoids, as well as dietary fiber mostly comprising fructans and inulins, which are prebiotics capable of supporting the growth of beneficial members of gut microbiota. In this study, we used the Human Gut Simulator system to assess the fermentation of oro-gastro-intestinally digested asparagus powder by the human gut microbiota.

Oncogenic potential of truncated-Gli3 via the Gsk3β/Gli3/AR-V7 axis in castration-resistant prostate cancer.

The functional activation of the androgen receptor (AR) and its interplay with the aberrant Hh/Gli cascade are pivotal in the progression of castration-resistant prostate cancer (CRPC) and resistance to AR-targeted therapies. Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation.