Therapeutic upregulation of DNA repair pathways: strategies and small molecule activators.

DNA repair activity diminishes with age and genetic mutations, leading to a significantly increased risk of cancer and other diseases. Upregulating the DNA repair system has emerged as a potential strategy to mitigate disease susceptibility while minimizing cytotoxic side effects. However, enhancing DNA repair activity presents significant challenges due to the inherent inefficiency in activator screening processes.

Revisiting the full blood count: Circulating blood cells and their role in coagulation.

There has been an expansion in our understanding of the multifaceted roles of circulating blood cells in regulating haemostasis and contributing to thrombosis. Notably, there is greater recognition of the interplay between coagulation with inflammation and innate immune activation and the contribution of leucocytes. The full blood count (FBC) is a time-honoured test in medicine; however, its components are often viewed in isolation and without consideration of their haemostatic and thrombotic potential.

The convergent model of coagulation.

It is increasingly apparent that the pathologic interplay between coagulation and innate immunity, ie, immunothrombosis, forms the common basis of many challenges across the boundaries of specialized medicine and cannot be fully explained by the conventional concepts of cascade and cell-based coagulation. To improve our understanding of coagulation, we propose a model of coagulation that converges with inflammation and innate immune activation as a unified response toward vascular injury. Evolutionarily integral to the convergent response are damage-associated molecular patterns, which are released as a consequence of injury.

Modulate the laser phase to improve the ns-LIBS spectrum signal based on orbital angular momentum.

Aiming to enhance the ns-LIBS signal, in this work, we introduced orbital angular momentum to modulate the laser phase of the Gaussian beam into the vortex beam. Under similar incident laser energy, the vortex beam promoted more uniform ablation and more ablation mass compared to the Gaussian beam, leading to elevated temperature and electron density in the laser-induced plasma. Consequently, the intensity of the ns-LIBS signal was improved.

Oral administration of bone marrow-derived mesenchymal stem cells attenuates intestinal injury in necrotizing enterocolitis.

Background: Necrotizing enterocolitis (NEC) is a major cause of morbidity in premature infants. However, effective treatment options for NEC are currently lacking.

Purpose: This study aimed to determine the optimal dose of intraperitoneally administered bone marrow-derived mesenchymal stem cells (BM-MSCs) and investigate the therapeutic potential of orally administered BM-MSCs in NEC.

Damage-associated cellular markers in the clinical and pathogenic profile of vaccine-induced immune thrombotic thrombocytopenia.

Background: Adenoviral vector-based COVID-19 vaccine-induced immune thrombotic thrombocytopenia (VITT) is rare but carries significant risks of mortality and long-term morbidity. The underlying pathophysiology of severe disease is still not fully understood. The objectives were to explore the pathophysiological profile and examine for clinically informative biomarkers in patients with severe VITT.

Rethinking coagulation: from enzymatic cascade and cell-based reactions to a convergent model involving innate immune activation.

Advancements in the conceptual thinking of hemostasis and thrombosis have been catalyzed by major developments within health research over several decades. The cascade model of coagulation was first described in the 1960s, when biochemistry gained prominence through innovative experimentation and technical developments. This was followed by the cell-based model, which integrated cellular coordination to the enzymology of clot formation and was conceptualized during the growth period in cell biology at the turn of the millennium.

Knocking down SOX2 overcomes the resistance of prostate cancer to castration via notch signaling.

Background: Castration-resistant prostate cancer (CRPC) is a terminal type of advanced cancer resistant to androgen deprivation therapy (ADT). Due to the poor therapeutic response of CRPC, novel treatment strategies are urgently required. This study aimed to clarify the regulatory roles of the SOX2/Notch axis in CRPC.

The protective effects of pirfenidone in preventing abdominal aortic aneurysm formation.

Vascular endothelial growth factor (VEGF)-mediated angiogenesis participates in the initiation and progression of abdominal aortic aneurysm (AAA). Pirfenidone is a compound that has anti-inflammatory and antioxidant properties and suppresses angiogenesis. Pirfenidone targets the extracellular matrix (ECM) and has therapeutic effects on fibrotic diseases.

Reversible 2'-OH acylation enhances RNA stability.

The presence of a hydroxyl group at the 2'-position in its ribose makes RNA susceptible to hydrolysis. Stabilization of RNAs for storage, transport and biological application thus remains a serious challenge, particularly for larger RNAs that are not accessible by chemical synthesis. Here we present reversible 2'-OH acylation as a general strategy to preserve RNA of any length or origin.

Cell-free histones and the cell-based model of coagulation.

The cell-based model of coagulation remains the basis of our current understanding of clinical hemostasis and thrombosis. Its advancement on the coagulation cascade model has enabled new prohemostatic and anticoagulant treatments to be developed. In the past decade, there has been increasing evidence of the procoagulant properties of extracellular, cell-free histones (CFHs).

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP.

Characterization of mesenchymal stem cells in human fetal bone marrow by single-cell transcriptomic and functional analysis.

Bone marrow mesenchymal stromal/stem cells (MSCs) are a heterogeneous population that can self-renew and generate stroma, cartilage, fat, and bone. Although a significant progress has been made toward recognizing about the phenotypic characteristics of MSCs, the true identity and properties of MSCs in bone marrow remain unclear. Here, we report the expression landscape of human fetal BM nucleated cells (BMNCs) based on the single-cell transcriptomic analysis.

Differential Expression of Pax6 Following Bilateral Common Carotid Artery Occlusion.

Background/aim: Chronic cerebral hypoperfusion causes neuronal damage involving cognitive impairment and development of dementia. Permanent bilateral common carotid artery occlusion (BCCAO) in rat models is used to study chronic cerebral hypoperfusion. Pax6 is used as an early neurogenesis marker which affects the maturation of neuronal cells.

A Small-Molecule Fluorescence Probe for Nuclear ATP.

Fluorescence monitoring of ATP in different organelles is now feasible with a few biosensors developed, which, however, show low sensitivity, limited biocompatibility, and accessibility. Small-molecule ATP probes that alleviate those limitations thus have received much attention recently, leading to a few ATP probes that target several organelles except for the nucleus. We disclose the first small-molecule probe that selectively detects nuclear ATP through reversible binding, with 25-fold fluorescence enhancement at pH 7.

A Phase II/III, Multicenter, Observer-blinded, Randomized, Non-inferiority and Safety, study of typhoid conjugate vaccine (EuTCV) compared to Typbar-TCV® in healthy 6 Months-45 years aged participants.

The typhoid conjugate vaccine (TCV) ensures a long-lasting protective immune response, requires fewer doses and is fit for children under 2 years of age. From Phase I study, EuTCV displayed considerable immunogenicity and reliable safety, thus endorsing further examination in Phase II/III trials. Therefore, a clinical Phase II/III study (NCT04830371) was conducted to evaluate its efficacy in healthy Filipino participants aged 6 months to 45 years through administration of the test vaccine (Arm A, B, and C) or comparator vaccine Typbar-TCV® (Arm D).

The Importance of Pore-Forming Toxins in Multiple Organ Injury and Dysfunction.

Background: Multiple organ injury and dysfunction often occurs in acute critical illness and adversely affects survival. However, in patients who survive, organ function usually recovers without permanent damage. It is, therefore, likely that there are reversible mechanisms, but this is poorly understood in the pathogenesis of multiple organ dysfunction syndrome (MODS).

A thickened formula reduces feeding-associated oxygen desaturation and bradycardia in preterm infants.

Background: Although preterm infants often experience desaturation or bradycardia during oral feeding, specific guidelines for its management are lacking.

Purpose: This study aimed to investigate the effects of a commercial thickened formula (TF) on oxygen saturation and heart rate stabilization during oral feeding in preterm infants.

Methods: This retrospective study included 122 infants born at a median (interquartile range [IQR]) 31+6 weeks (29+4 -34+6 weeks) of gestation weighing 1,725 g (1,353-2,620 g) and fed commercial cornstarch-containing TF due to feeding-associated desaturation or bradycardia.

Shenqi granule upregulates CD2AP and α-actinin4 and activates autophagy through regulation of mTOR/ULK1 pathway in MPC5 cells.

Ethnopharmacological Relevance: The incidence of membranous nephropathy (MN) continues to rise globally. Shenqi granule (SQ), composed of thirteen Chinese medicinal herbs, has clinical efficacy in the treatment of MN and has been used in China for decades. However, the mechanism behind this effect remains unclear.