Enhanced brain delivery of hypoxia-sensitive liposomes by hydroxyurea for rescue therapy of hyperacute ischemic stroke.

Ischemic stroke is characterized by high morbidity, disability, and mortality. Unfortunately, the only FDA-approved pharmacological thrombolytic, alteplase, has a narrow therapeutic window of only 4.5 h.

Anti-Inflammatory, Anti-Oxidative and Anti-Apoptotic Effects of Thymol and 24-Epibrassinolide in Zebrafish Larvae.

Thymol (THY) and 24-epibrassinolide (24-EPI) are two examples of plant-based products with promising therapeutic effects. In this study, we investigated the anti-inflammatory, antioxidant and anti-apoptotic effects of the THY and 24-EPI. We used zebrafish () larvae transgenic line (Tg(GFP)) to evaluate the recruitment of neutrophils as an inflammatory marker to the site of injury after tail fin amputation.

Leukocyte Imbalances in Mucopolysaccharidoses Patients.

Mucopolysaccharidoses (MPSs) are rare inherited lysosomal storage diseases (LSDs) caused by deficient activity in one of the enzymes responsible for glycosaminoglycans lysosomal degradation. MPS II is caused by pathogenic mutations in the gene, leading to deficient activity of the enzyme iduronate-2-sulfatase, which causes dermatan and heparan sulfate storage in the lysosomes. In MPS VI, there is dermatan sulfate lysosomal accumulation due to pathogenic mutations in the gene, leading to arylsulfatase B deficiency.

Survival benefits and challenges of adjuvant chemotherapy for high-grade osteosarcoma: a population-based study.

Background: Osteosarcoma is the most prevalent primary malignant bone tumor. The primary treatment for osteosarcoma is a combination of chemotherapy and surgery. However, there has been no recent progress in the role of chemotherapy in improving the long-term survival of osteosarcoma patients.

Pentaketides and 5--Hydroxyphenyl-2-pyridone Derivative from the Culture Extract of a Marine Sponge-Associated Fungus KUFA0732.

Five undescribed pentaketide derivatives, ()-6,8-dihydroxy-4,5-dimethyl-3-methylidene-3,4-dihydro-1-2-benzopyran-1-one (), [(3,4)-3,8-dihydroxy-6-methoxy-4,5-dimethyl-1-oxo-3,4-dihydro-1-isochromen-3-yl]methyl acetate (), ()-5, 7-dimethoxy-3-((-(1-hydroxyethyl)-3,4-dimethylisobenzofuran-1(3)-one (), ()-7-hydroxy-3-(()-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran 1(3)-one (), and a -hydroxyphenyl-2-pyridone derivative, avellaneanone (), were isolated together with the previously reported ()-3-acetyl-7-hydroxy-5-methoxy-3,4-dimethylisobenzofuran-1(3)-one (), ()-7-hydroxy-3-(()-1-hydroxyethyl)-5-methoxy-3,4-dimethylisobenzofuran-1(3)-one () and isosclerone (), from the ethyl acetate extract of a culture of a marine sponge-derived fungus, KUFA0732. The structures of the undescribed compounds were elucidated using 1D and 2D NMR, as well as high-resolution mass spectral analyses. The absolute configurations of the stereogenic carbons in , , , and were established by X-ray crystallographic analysis.

Intraoperative fluoroscopic radiation in orthopedic trauma: correlation with surgery type and surgeon experience.

Background: While fluoroscopy is widely used in orthopedic trauma surgeries, it is associated with harmful effects and should, therefore, be minimized. However, reference values for these surgeries have not been defined, and it is not known how surgeon experience affects these factors. The aims of this study were to analyze the radiation emitted and exposure time for common orthopedic trauma surgeries and to assess whether they are affected by surgeon experience.

Pro-inflammatory polarization and colorectal cancer modulate alternative and intronic polyadenylation in primary human macrophages.

Introduction: Macrophages are essential cells of the immune system that alter their inflammatory profile depending on their microenvironment. Alternative polyadenylation in the 3'UTR (3'UTR-APA) and intronic polyadenylation (IPA) are mechanisms that modulate gene expression, particularly in cancer and activated immune cells. Yet, how polarization and colorectal cancer (CRC) cells affect 3'UTR-APA and IPA in primary human macrophages was unclear.

Ageing in the brain: mechanisms and rejuvenating strategies.

Ageing is characterized by the progressive loss of cellular homeostasis, leading to an overall decline of the organism's fitness. In the brain, ageing is highly associated with cognitive decline and neurodegenerative diseases. With the rise in life expectancy, characterizing the brain ageing process becomes fundamental for developing therapeutic interventions against the increased incidence of age-related neurodegenerative diseases and to aim for an increase in human life span and, more importantly, health span.

Complex Regulation of Gamma-Hemolysin Expression Impacts Staphylococcus aureus Virulence.

Staphylococcus aureus gamma-hemolysin CB (HlgCB) is a core-genome-encoded pore-forming toxin that targets the C5a receptor, similar to the phage-encoded Panton-Valentine leucocidin (PVL). Absolute quantification by mass spectrometry of HlgCB in 39 community-acquired pneumonia (CAP) isolates showed considerable variations in the HlgC and HlgB yields between isolates. Moreover, although HlgC and HlgB are encoded on a single operon, their levels were dissociated in 10% of the clinical strains studied.

Accuracy of Invisalign on Upper Incisors: A Systematic Review.

The current systematic review appraises the effectiveness of the types of tooth movements performed with Invisalign clear aligner on the maxillary incisors. An electronic literature search of published trials was performed through PubMed, LILACS, Scopus, Cochrane Library, and Web of Science databases, and selected journals, from 2009 to 2020. Out of 291 references, five relevant publications were identified for analysis: four studies were performed retrospectively and one prospectively, all non-randomized.

Genomic and Transcriptomic Remodeling by Neoadjuvant Chemoradiotherapy (nCRT) and the Indicative Role of Acquired INDEL Percentage for nCRT Efficacy in Esophageal Squamous Cell Carcinoma.

Purpose: The effect of genomic factors on the response of patients with esophageal squamous cell carcinoma (ESCC) to neoadjuvant chemoradiotherapy (nCRT), as well as how nCRT influences the genome and transcriptome of ESCC, remain largely unknown.

Methods And Materials: In total, 137 samples from 57 patients with ESCC undergoing nCRT were collected and subjected to whole-exome sequencing and RNA sequencing analysis. Genetic and clinicopathologic factors were compared between the patients achieving pathologic complete response and patients not achieving pathologic complete response.

Clinical profiling of specific diagnostic subgroups of women with chronic pelvic pain.

Introduction: Chronic pelvic pain (CPP) is a common condition affecting up to 26.6% of women, with many suffering for several years before diagnosis and/or treatment. Its clinical presentation is varied and there are frequently comorbid conditions both within and outside the pelvis.

Sequential therapy with crizotinib and a second-generation ALK inhibitor versus direct therapy of a second-generation ALK inhibitor in -positive advanced lung cancer: a real-world study.

Background: There are few real-world studies in which the efficacy of sequential crizotinib and second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are compared with direct therapy of second-generation ALK TKI in -positive advanced lung cancer.

Methods: Between May 2014 and October 2022, 211 patients from the Zhejiang Cancer Hospital who harbored rearrangement were analyzed. Of these patients, 115 received crizotinib with sequential second-generation ALK TKIs, and 96 patients received a second-generation ALK TKI directly.

Liquid biopsy in the management of advanced lung cancer: Implementation and practical aspects.

Non-small-cell lung cancer (NSCLC) is a major cause of cancer-related death worldwide. In recent years, the discovery of actionable molecular alterations has changed the treatment paradigm of the disease. Tissue biopsies have been the gold standard for the identification of targetable alterations but present several limitations, calling for alternatives to detect driver and acquired resistance alterations.

A RhoA-mediated biomechanical response in Schwann cells modulates peripheral nerve myelination.

Myelin improves axonal conduction velocity and is essential for nerve development and regeneration. In peripheral nerves, Schwann cells depend on bidirectional mechanical and biochemical signaling to form the myelin sheath but the mechanism underlying this process is not understood. Rho GTPases are integrators of "outside-in" signaling that link cytoskeletal dynamics with cellular architecture to regulate morphology and adhesion.

Anillin and the microtubule bundler PRC1 maintain myosin in the contractile ring to ensure completion of cytokinesis.

Cytokinesis is the last step of cell division, when one cell physically divides into two cells. Cytokinesis is driven by an equatorial contractile ring and signals from antiparallel microtubule bundles (the central spindle) that form between the two masses of segregating chromosomes. Bundling of central spindle microtubules is essential for cytokinesis in cultured cells.

Structural insights into mechanisms of Argonaute protein-associated NADase activation in bacterial immunity.

Nicotinamide adenine dinucleotide (NAD) is a central metabolite in cellular processes. Depletion of NAD has been demonstrated to be a prevalent theme in both prokaryotic and eukaryotic immune responses. Short prokaryotic Argonaute proteins (Agos) are associated with NADase domain-containing proteins (TIR-APAZ or SIR2-APAZ) encoded in the same operon.

Role of nanotechnology in the prolonged release of drugs by the subcutaneous route.

Introduction: Subcutaneous physiology is distinct from other parenteral routes that benefit the administration of prolonged-release formulations. A prolonged-release effect is particularly convenient for treating chronic diseases because it is associated with complex and often prolonged posologies. Therefore, drug-delivery systems focused on nanotechnology are proposed as alternatives that can overcome the limitations of current therapeutic regimens and improve therapeutic efficacy.

The impact of psychostimulants on central and peripheral neuro-immune regulation: a scoping review of cytokine profiles and their implications for addiction.

It is now well-accepted that psychostimulants act on glial cells causing neuroinflammation and adding to the neurotoxic effects of such substances. Neuroinflammation can be described as an inflammatory response, within the CNS, mediated through several cytokines, reactive oxygen species, chemokines and other inflammatory markers. These inflammatory players, in particular cytokines, play important roles.

Global hotspots and emerging trends in 3D bioprinting research.

Three-dimensional (3D) bioprinting is an advanced tissue engineering technique that has received a lot of interest in the past years. We aimed to highlight the characteristics of articles on 3D bioprinting, especially in terms of research hotspots and focus. Publications related to 3D bioprinting from 2007 to 2022 were acquired from the Web of Science Core Collection database.

Photosensitive small extracellular vesicles regulate the immune microenvironment of triple negative breast cancer.

Currently, the treatment of triple-negative breast cancer (TNBC) is limited by the special pathological characteristics of this disease. In recent years, photodynamic therapy (PDT) has created new hope for the treatment of TNBC. Moreover, PDT can induce immunogenic cell death (ICD) and improve tumor immunogenicity.

Neoadjuvant Pyrotinib plus Trastuzumab, Docetaxel, and Carboplatin in Early or Locally Advanced Human Epidermal Receptor 2-Positive Breast Cancer in China: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Introduction: This multicenter, randomized, double-blind, placebo-controlled phase 2 trial compared the efficacy, and safety of adding pyrotinib to trastuzumab, docetaxel, and carboplatin versus placebo, trastuzumab, docetaxel, and carboplatin in Chinese patients with human epidermal receptor 2 (HER2)-positive early or locally advanced breast cancer ( View Article and Find Full Text PDF

Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34).