Pelvic congestion syndrome analysis through quantitative 2-dimensional phase-contrast magnetic resonance imaging: A promising vision from an observational cohort study.

BACKGROUND: To examine the application of quantitative 2-dimensional phase-contrast magnetic resonance imaging (2D PC-MRI) for treating patients with pelvic congestion syndrome (PCS). MATERIALS AND METHODS: We conducted a retrospective cross-sectional analysis by using quantitative 2D PC-MRI data enrolled between April 2017 and Sep 2023. In addition, 32 healthy female controls (HCs) were included. RESULTS: Most patients with PCS presented with chronic pelvic pain and more than half had extra-pelvic venous symptoms (80/81, 98% and 45/81, 56%, respectively). Quantitative 2D PC-MRI analyzed the 81 patients with PCS, 239 patients without PCS, and 32 HCs. The patients with PCS had higher stroke volume (SV), absolute SV (ASV), and mean flux (MF) in the calf region (interstitial pixel shift) than did the HCs. In the left gonadal vein, the patients with PCS had higher SV, backward flow volume (BFV), ASV, and MF and lower forward flow volume (FFV), stroke distance (SD), and mean velocity (MV) than did the HCs. However, the patients with PCS had lower SV, FFV, MF, SD, and MV in the great saphenous veins. Quantitative 2D PC-MRI analysis revealed that the PCS group had higher SV, FFV, BFV, ASV, and MF in the calf region than did the non-PCS group. The variables that most strongly differentiated the patients with PCS from the HCs were SV in the great saphenous veins, SD in the great saphenous veins and left gonadal vein, and MV in the great saphenous veins and left gonadal vein. Caudal flow in the left gonadal vein was identified in half of the patients with PCS (39/81, 48.1%); 14 of them received embolization for left gonadal vein. CONCLUSIONS: In additional to providing an objective 3-dimensional morphology of the pelvic veins and extra-pelvic leaks, quantitative 2D PC-MRI analysis reveals distinct hemodynamic profiles between patients with PCS, those without PCS, and HCs, especially in the gonadal veins and regional perfusion of the calves.

Formononetin Alleviates Ischemic Acute Kidney Injury by Regulating Macrophage Polarization through KLF6/STAT3 Pathway.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1ß) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-[Formula: see text]. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

SARS-CoV-2 pathogenesis in an angiotensin II-induced heart-on-a-chip disease model and extracellular vesicle screening.

Adverse cardiac outcomes in COVID-19 patients, particularly those with preexisting cardiac disease, motivate the development of human cell-based organ-on-a-chip models to recapitulate cardiac injury and dysfunction and for screening of cardioprotective therapeutics. Here, we developed a heart-on-a-chip model to study the pathogenesis of SARS-CoV-2 in healthy myocardium established from human induced pluripotent stem cell (iPSC)-derived cardiomyocytes and a cardiac dysfunction model, mimicking aspects of preexisting hypertensive disease induced by angiotensin II (Ang II). We recapitulated cytopathic features of SARS-CoV-2-induced cardiac damage, including progressively impaired contractile function and calcium handling, apoptosis, and sarcomere disarray. SARS-CoV-2 presence in Ang II-treated hearts-on-a-chip decreased contractile force with earlier onset of contractile dysfunction and profoundly enhanced inflammatory cytokines compared to SARS-CoV-2 alone. Toward the development of potential therapeutics, we evaluated the cardioprotective effects of extracellular vesicles (EVs) from human iPSC which alleviated the impairment of contractile force, decreased apoptosis, reduced the disruption of sarcomeric proteins, and enhanced beta-oxidation gene expression. Viral load was not affected by either Ang II or EV treatment. We identified MicroRNAs miR-20a-5p and miR-19a-3p as potential mediators of cardioprotective effects of these EVs.

Independent organelle and organelle-organelle interactions: essential mechanisms for malignant gynecological cancer cell survival.

Different eukaryotic cell organelles (e.g., mitochondria, endoplasmic reticulum, lysosome) are involved in various cancer processes, by dominating specific cellular activities. Organelles cooperate, such as through contact points, in complex biological activities that help the cell regulate energy metabolism, signal transduction, and membrane dynamics, which influence survival process. Herein, we review the current studies of mechanisms by which mitochondria, endoplasmic reticulum, and lysosome are related to the three major malignant gynecological cancers, and their possible therapeutic interventions and drug targets. We also discuss the similarities and differences of independent organelle and organelle-organelle interactions, and their applications to the respective gynecological cancers; mitochondrial dynamics and energy metabolism, endoplasmic reticulum dysfunction, lysosomal regulation and autophagy, organelle interactions, and organelle regulatory mechanisms of cell death play crucial roles in cancer tumorigenesis, progression, and response to therapy. Finally, we discuss the value of organelle research, its current problems, and its future directions.

Biomaterials for immunomodulation in wound healing.

The substantial economic impact of non-healing wounds, scarring, and burns stemming from skin injuries is evident, resulting in a financial burden on both patients and the healthcare system. This review paper provides an overview of the skin's vital role in guarding against various environmental challenges as the body's largest protective organ and associated developments in biomaterials for wound healing. We first introduce the composition of skin tissue and the intricate processes of wound healing, with special attention to the crucial role of immunomodulation in both acute and chronic wounds. This highlights how the imbalance in the immune response, particularly in chronic wounds associated with underlying health conditions such as diabetes and immunosuppression, hinders normal healing stages. Then, this review distinguishes between traditional wound-healing strategies that create an optimal microenvironment and recent peptide-based biomaterials that modulate cellular processes and immune responses to facilitate wound closure. Additionally, we highlight the importance of considering the stages of wounds in the healing process. By integrating advanced materials engineering with an in-depth understanding of wound biology, this approach holds promise for reshaping the field of wound management and ultimately offering improved outcomes for patients with acute and chronic wounds.

Metabolism, fibrosis, and apoptosis: The effect of lipids and their derivatives on keloid formation.

Keloids, pathological scars resulting from skin trauma, have traditionally posed significant clinical management challenges due to their persistence and high recurrence rates. Our research elucidates the pivotal roles of lipids and their derivatives in keloid development, driven by underlying mechanisms of abnormal cell proliferation, apoptosis, and extracellular matrix deposition. Key findings suggest that abnormalities in arachidonic acid (AA) synthesis and non-essential fatty acid synthesis are integral to keloid formation. Further, a complex interplay exists between lipid derivatives, notably butyric acid (BA), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), and the regulation of hyperfibrosis. Additionally, combinations of docosahexaenoic acid (DHA) with BA and 15-deoxy-Δ12,14-Prostaglandin J2 have exhibited pronounced cytotoxic effects. Among sphingolipids, ceramide (Cer) displayed limited pro-apoptotic effects in keloid fibroblasts (KFBs), whereas sphingosine 1-phosphate (S1P) was found to promote keloid hyperfibrosis, with its analogue, FTY720, demonstrating contrasting benefits. Both Vitamin D and hexadecylphosphorylcholine (HePC) showed potential antifibrotic and antiproliferative properties, suggesting their utility in keloid management. While keloids remain a prevalent concern in clinical practice, this study underscores the promising potential of targeting specific lipid molecules for the advancement of keloid therapeutic strategies.

Highly sensitive and selective detection of triphosgene with a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe.

In this work, a 2-(2'-hydroxyphenyl)benzimidazole derived fluorescent probe, 2-(2'-hydroxy-4'-aminophenyl)benzimidazole (4-AHBI), was synthesized and its fluorescent behavior toward triphosgene were evaluated. The results showed that 4-AHBI exhibited high sensitivity (limit of detection, 0.08 nM) and excellent selectivity for triphosgene over other acyl chlorides including phosgene in CH2Cl2 solution. Moreover, 4-AHBI loaded test strips were prepared for the practical sensing of triphosgene.

Effect of exogenous hydrogen sulfide in the nucleus tractus solitarius on gastric motility in rats.

BACKGROUND: Hydrogen sulfide (H2S) is a recently discovered gaseous neurotransmitter in the nervous and gastrointestinal systems. It exerts its effects through multiple signaling pathways, impacting various physiological activities. The nucleus tractus solitarius (NTS), a vital nucleus involved in visceral sensation, was investigated in this study to understand the role of H2S in regulating gastric function in rats. AIM: To examine whether H2S affects the nuclear factor kappa-B (NF-κB) and transient receptor potential vanilloid 1 pathways and the neurokinin 1 (NK1) receptor in the NTS. METHODS: Immunohistochemical and fluorescent double-labeling techniques were employed to identify cystathionine beta-synthase (CBS) and c-Fos co-expressed positive neurons in the NTS during rat stress. Gastric motility curves were recorded by inserting a pressure-sensing balloon into the pylorus through the stomach fundus. Changes in gastric motility were observed before and after injecting different doses of NaHS (4 nmol and 8 nmol), physiological saline, Capsazepine (4 nmol) + NaHS (4 nmol), pyrrolidine dithiocarbamate (PDTC, 4 nmol) + NaHS (4 nmol), and L703606 (4 nmol) + NaHS (4 nmol). RESULTS: We identified a significant increase in the co-expression of c-Fos and CBS positive neurons in the NTS after 1 h and 3 h of restraint water-immersion stress compared to the expressions observed in the control group. Intra-NTS injection of NaHS at different doses significantly inhibited gastric motility in rats (P < 0.01). However, injection of saline, first injection NF-κB inhibitor PDTC or transient receptor potential vanilloid 1 (TRPV1) antagonist Capsazepine or NK1 receptor blockers L703606 and then injection NaHS did not produce significant changes (P > 0.05). CONCLUSION: NTS contains neurons co-expressing CBS and c-Fos, and the injection of NaHS into the NTS can suppress gastric motility in rats. This effect may be mediated by activating TRPV1 and NK1 receptors via the NF-κB channel.

All-Atom Molecular Dynamics Simulations of Membrane-Spanning DNA Origami Nanopores.

Building on the recent technological advances, all-atom molecular dynamics (MD) simulations have become an indispensable tool to study the molecular behavior at nanoscale. Molecular simulations have been used to characterize the structure, dynamics, and mechanical and electrical properties of DNA origami objects. In this chapter we describe a method to build all-atom model of lipid-spanning DNA origami nanopores and perform molecular dynamics simulations in explicit electrolyte solutions.