Oxygen-defect bismuth oxychloride nanosheets for ultrasonic cavitation effect enhanced sonodynamic and second near-infrared photo-induced therapy of breast cancer.

Sonodynamic therapy (SDT) relies heavily on the presence of oxygen to induce cell death. Its effectiveness is thus diminished in the hypoxic regions of tumor tissue. To address this issue, the exploration of ultrasound-based synergistic treatment modalities has become a significant research focus. Here, we report an ultrasonic cavitation effect enhanced sonodynamic and 1208 nm photo-induced cancer treatment strategy based on thermoelectric/piezoelectric oxygen-defect bismuth oxychloride nanosheets (BNs) to realize the high-performance eradication of tumors. Upon ultrasonic irradiation, the local high temperature and high pressure generated by the ultrasonic cavitation effect combined with the thermoelectric and piezoelectric effects of BNs create a built-in electric field. This facilitates the separation of carriers, increasing their mobility and extending their lifetimes, thereby greatly improving the effectiveness of SDT and NIR-Ⅱ phototherapy on hypoxia. The Tween-20 modified BNs (TBNs) demonstrate ∼88.6 % elimination rate against deep-seated tumor cells under hypoxic conditions. In vivo experiments confirm the excellent antitumor efficacy of TBNs, achieving complete tumor elimination within 10 days with no recurrences. Furthermore, due to the high X-ray attenuation of Bi and excellent NIR-Ⅱ absorption, TBNs enable precise cancer diagnosis through photoacoustic (PA) imaging and computed tomography (CT).

Discrete Wavelet Transformation for the Sensitive Detection of Ultrashort Radiation Pulse with Radiation-induced Acoustics.

Radiation-induced acoustics (RIA) shows promise in advancing radiological imaging and radiotherapy dosimetry methods. However, RIA signals often require extensive averaging to achieve reasonable signal-to-noise ratios, which increases patient radiation exposure and limits real-time applications. Therefore, this paper proposes a discrete wavelet transform (DWT) based filtering approach to denoise the RIA signals and avoid extensive averaging. The algorithm was benchmarked against low-pass filters and tested on various types of RIA sources, including low-energy X-rays, high-energy X-rays, and protons. The proposed method significantly reduced the required averages (1000 times less averaging for low-energy X-ray RIA, 32 times less averaging for high-energy X-ray RIA, and 4 times less averaging for proton RIA) and demonstrated robustness in filtering signals from different sources of radiation. The coif5 wavelet in conjunction with the sqtwolog threshold selection algorithm yielded the best results. The proposed DWT filtering method enables high-quality, automated, and robust filtering of RIA signals, with a performance similar to low-pass filtering, aiding in the clinical translation of radiation-based acoustic imaging for radiology and radiation oncology.

Commentary: Early-in-life Isoflurane Exposure Alters Resting-State Functional Connectivity in Juvenile Non-human Primates - a Role for Neuroinflammation?

The concern about anesthesia-induced developmental neurotoxicity (AIDN) in infants and young children arises from animal studies indicating potential long-term neurobehavioral impairments following early-in-life anesthesia exposure. While initial clinical studies provided ambiguous results, recent prospective assessments in children indicate associations between early-in-life anesthesia exposure and later behavioral alterations. Ethical constraints and confounding factors in clinical studies pose challenges in establishing a direct causal link and in investigating its mechanisms. This commentary on a recent study in non-human primates (NHPs) focuses on exploring the role of neuroinflammation and alterations in brain functional connectivity in the behavioral impairments following early-in-life anesthesia exposure. In juvenile NHPs, chronic astrogliosis in the amygdala correlates with alterations in functional connectivity between this area with other regions of the brain and with the behavioral impairments, suggesting a potential mechanism for AIDN. Despite acknowledging the study's limitations, these findings emphasize the need for further research with larger cohorts to confirm these associations and to establish a causal link between the neuroinflammation and the behavioral alterations associated with early-in-life anesthesia exposure.

Stretch of the papillary insertion triggers reentrant arrhythmia: an in silico patient study.

Background: The electrophysiological mechanism connecting mitral valve prolapse (MVP), premature ventricular complexes and life-threatening ventricular arrhythmia is unknown. A common hypothesis is that stretch activated channels (SACs) play a significant role. SACs can trigger depolarizations or shorten repolarization times in response to myocardial stretch. Through these mechanisms, pathological traction of the papillary muscle (PM), as has been observed in patients with MVP, may induce irregular electrical activity and result in reentrant arrhythmia. Methods: Based on a patient with MVP and mitral annulus disjunction, we modeled the effect of excessive PM traction in a detailed medical image-derived ventricular model by activating SACs in the PM insertion region. By systematically varying the onset of SAC activation following sinus pacing, we identified vulnerability windows for reentry with 1 ms resolution. We explored how reentry was affected by the SAC reversal potential ( E SAC ) and the size of the region with simulated stretch (SAC region). Finally, the effect of global or focal fibrosis, modeled as reduction in tissue conductivity or mesh splitting (fibrotic microstructure), was investigated. Results: In models with healthy tissue or fibrosis modeled solely as CV slowing, we observed two vulnerable periods of reentry: For E SAC of -10 and -30 mV, SAC activated during the T-wave could cause depolarization of the SAC region which lead to reentry. For E SAC of -40 and -70 mV, SAC activated during the QRS complex could result in early repolarization of the SAC region and subsequent reentry. In models with fibrotic microstructure in the SAC region, we observed micro-reentries and a larger variability in which times of SAC activation triggered reentry. In these models, 86% of reentries were triggered during the QRS complex or T-wave. We only observed reentry for sufficiently large SAC regions ( > = 8 mm radius in models with healthy tissue). Conclusion: Stretch of the PM insertion region following sinus activation may initiate ventricular reentry in patients with MVP, with or without fibrosis. Depending on the SAC reversal potential and timing of stretch, reentry may be triggered by ectopy due to SAC-induced depolarizations or by early repolarization within the SAC region.

Variable positive end-expiratory pressure in an experimental model of acute respiratory distress syndrome: an advanced ventilation modality.

Background: Introducing variability in tidal volume, ventilatory frequency, or both is beneficial during mechanical ventilation in acute respiratory distress syndrome (ARDS). We investigated whether applying cycle-by-cycle variability in the positive end-expiratory pressure (PEEP) exerts beneficial effect on lung function in a model of ARDS. Methods: Rabbits with lung injury were randomly allocated to receive mechanical ventilation for 6 h by applying a pressure-controlled mode with constant PEEP of 7 cm H2O (PC group: n=6) or variable PEEP (VEEP) with a coefficient of variation of 21.4%, range 4-10 cm H2O (PC-VEEP group; n=6). Lung oxygenation index (Pao2/FiO2) after 6 h of ventilation (H6) was the primary outcome and respiratory mechanics, lung volume, intrapulmonary shunt, and lung inflammatory markers were secondary outcomes. Results: After lung injury, both groups presented moderate-to-severe ARDS (Pao2/FiO2 <27 kPa). The Pao2/FiO2 was significantly higher in the PC-VEEP group than in the PC group at H6 (12.3 [sd 3.5] vs 19.2 [7.2] kPa, P=0.013) and a lower arterial partial pressure of CO2 at 1-3 h (P<0.02). The ventilation-induced increases in airway resistance and tissue elastance were prevented by PC-VEEP. There was no evidence for a difference in minute volume, driving pressure, end-tidal CO2, lung volumes, intrapulmonary shunt fraction, and cytokines between the ventilation modes. Conclusions: Prolonged mechanical ventilation with cycle-by-cycle VEEP prevents deterioration in gas exchange and respiratory mechanics in a model of ARDS, suggesting the benefit of this novel ventilation strategy to optimise gas exchange without increasing driving pressure and lung overdistension.

Direct electron beam writing of silver using a ß-diketonate precursor: first insights.

Direct electron beam writing is a powerful tool for fabricating complex nanostructures in a single step. The electron beam locally cleaves the molecules of an adsorbed gaseous precursor to form a deposit, similar to 3D printing but without the need for a resist or development step. Here, we employ for the first time a silver ß-diketonate precursor for focused electron beam-induced deposition (FEBID). The used compound (hfac)AgPMe3 operates at an evaporation temperature of 70-80 °C and is compatible with commercially available gas injection systems used in any standard scanning electron microscope. Growth of smooth 3D geometries could be demonstrated for tightly focused electron beams, albeit with low silver content in the deposit volume. The electron beam-induced deposition proved sensitive to the irradiation conditions, leading to varying compositions of the deposit and internal inhomogeneities such as the formation of a layered structure consisting of a pure silver layer at the interface to the substrate covered by a deposit layer with low silver content. Imaging after the deposition process revealed morphological changes such as the growth of silver particles on the surface. While these effects complicate the application for 3D printing, the unique deposit structure with a thin, compact silver film beneath the deposit body is interesting from a fundamental point of view and may offer additional opportunities for applications.

Sclerotic prostate cancer bone metastasis: woven bone lesions with a twist.

Bone metastases are the most severe and prevalent consequences of prostate cancer (PC), affecting more than 80% of patients with advanced PC. PCBMs generate pain, pathological fractures, and paralysis. As modern therapies increase survival, more patients are suffering from these catastrophic consequences. Radiographically, PCBMs are predominantly osteosclerotic, but the mechanisms of abnormal bone formation and how this pathological increase in bone density is related to fractures are unclear. In this study, we conducted a comprehensive analysis on a cohort of 76 cadaveric PCBM specimens and 12 cancer-free specimens as controls. We used micro-computed tomography to determine 3D organization and quantify bone characteristics, quantitative backscattering electron microscopy to characterize mineral content and details in bone structure, nanoindentation to determine mechanical properties, and histological and immunohistochemical analysis of bone structure and composition. We define 4 PCBM phenotypes: osteolytic, mixed lytic-sclerotic, and 2 subgroups of osteosclerotic lesions-those with residual trabeculae, and others without residual trabeculae. The osteosclerotic lesions are characterized by the presence of abnormal bone accumulated on trabeculae surfaces and within intertrabecular spaces. This abnormal bone is characterized by higher lacunae density, abnormal lacunae morphology, and irregular lacunae orientation. However, mineral content, hardness, and elastic modulus at micron-scale were indistinguishable between this irregular bone and residual trabeculae. The collagen matrix of this abnormal bone presents with irregular organization and a prominent collagen III composition. These characteristics suggest that osteosclerotic PCBMs initiate new bone deposition as woven bone; however, the lack of subsequent bone remodeling, absence of lamellar bone deposition on its surface, and presence of collagen III distinguish this pathologic matrix from conventional woven bone. Although the mineralized matrix retains normal bone hardness and stiffness properties, the lack of fibril anisotropy presents a compromised trabecular structure, which may have clinical implications.

Comparative assessment of autologous and allogeneic iNKT cell transfer in iNKT cell-based immunotherapy.

Invariant natural killer T (iNKT) cells are a small subset of T lymphocytes that release large amounts of cytokines such as IFN-γ and exhibit cytotoxic activity upon activation, inducing strong anti-tumor effects. Harnessing the anti-tumor properties of iNKT cells, iNKT cell-based immunotherapy has been developed to treat cancer patients. In one of the iNKT cell-based immunotherapies, two approaches are utilized, namely, active immunotherapy or adoptive immunotherapy, the latter involving the ex vivo expansion and subsequent administration of iNKT cells. There are two sources of iNKT cells for adoptive transfer, autologous and allogeneic, each with its own advantages and disadvantages. Here, we assess clinical trials conducted over the last decade that have utilized iNKT cell adoptive transfer as iNKT cell-based immunotherapy, categorizing them into two groups based on the use of autologous iNKT cells or allogeneic iNKT cells.

GDF-15 Alleviates Hypoxia-Reoxygenation-Induced Damage to Human Placental Vascular Endothelial Cells by Regulating SIRT1.

OBJECTIVE: Pregnancy-induced hypertension (PIH) is a common disease during pregnancy, which arises from maternal placental vascular endothelial cell dysfunction. Growth differentiation factor 15 (GDF-15) has a protective effect on the cardiovascular system. The purpose of this study is to explore the protective effect of GDF-15 against hypoxia-reoxygenation (H/R)-induced damage to human placental vascular endothelial cells (HPVECs) and the regulatory mechanism of SIRT1 in this effect. METHODS: Serum samples from healthy pregnant women and those with PIH were collected, and their GDF-15 and SIRT1 levels were examined. HPVECs were cultured in vitro and induced with H/R and GDF-15 at varying concentrations. The optimal concentration of GDF-15 in protecting HPVECs was determined by measuring cell viability via the CCK-8 assay. In H/R-induced HPVECs treated with GDF-15 and compound C (the AMPK inhibitor), expression levels of SIRT1, p-AMPK, and t-AMPK were detected. Cell apoptosis was examined by flow cytometry. RESULTS: Serum SIRT1 and GDF-15 were significantly higher in healthy pregnant women than in PIH patients. Suppressed viability and activated apoptosis in H/R-induced HPVECs were partially reversed by the treatment of GDF-15 at a concentration of 100 ng/mL. H/R induction significantly downregulated SIRT1 and p-AMPK in HPVECs, which were then upregulated by GDF-15. Moreover, the protective effect of GDF-15 on H/R-induced HPVECs was blocked by inhibiting the AMPK signaling pathway. CONCLUSION: GDF-15 protects against H/R-inhibited cell viability and H/R-stimulated apoptosis in HPVECs by activating the AMPK signaling pathway to upregulate SIRT1.

Gradient conducting polymer surfaces with netrin-1-conjugation promote axon guidance and neuron transmission of human iPSC-derived retinal ganglion cells.

Major advances have been made in utilizing human-induced pluripotent stem cells (hiPSCs) for regenerative medicine. Nevertheless, the delivery and integration of hiPSCs into target tissues remain significant challenges, particularly in the context of retinal ganglion cell (RGC) restoration. In this study, we introduce a promising avenue for providing directional guidance to regenerated cells in the retina. First, we developed a technique for construction of gradient interfaces based on functionalized conductive polymers, which could be applied with various functionalized ehthylenedioxythiophene (EDOT) monomers. Using a tree-shaped channel encapsulated with a thin PDMS and a specially designed electrochemical chamber, gradient flow generation could be converted into a functionalized-PEDOT gradient film by cyclic voltammetry. The characteristics of the successfully fabricated gradient flow and surface were analyzed using fluorescent labels, time of flight secondary ion mass spectrometry (TOF-SIMS), and X-ray photoelectron spectroscopy (XPS). Remarkably, hiPSC-RGCs seeded on PEDOT exhibited improvements in neurite outgrowth, axon guidance and neuronal electrophysiology measurements. These results suggest that our novel gradient PEDOT may be used with hiPSC-based technologies as a potential biomedical engineering scaffold for functional restoration of RGCs in retinal degenerative diseases and optic neuropathies.

Therapeutic efficacy of JEW-M449, an anti-TCTP monoclonal antibody, administered via the nasal route in a BALB/c mouse model of ovalbumin-induced acute asthma.

Numerous studies have highlighted the role of translationally controlled tumor protein (TCTP) as a key inflammatory mediator of asthma and allergies. Our previous study revealed that blocking the cytokine-like activity of TCTP using JEW-M449, an anti-TCTP monoclonal antibody (mAb), alleviated allergic inflammation in asthmatic mice. This study aimed to determine whether directly delivering JEW-M449 into the respiratory tract is a more effective way of mitigating airway inflammation in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation than delivering this antibody via the intraperitoneal (IP) route. OVA-sensitized mice were intranasally administered JEW-M449 to enable its direct delivery to the respiratory tract before OVA challenge. We evaluated the changes in the levels of bronchoalveolar lavage fluid (BALF) cells, T helper type 2 (Th2) cytokines, OVA-specific immunoglobulin E (IgE), and histopathological alterations in the lung tissues. Intranasal (IN) administration of JEW-M449 significantly ameliorated the pathological changes associated with OVA-induced lung injury, including reduced inflammatory cell infiltration and mucus hypersecretion. Mice IN administered JEW-M449 also showed decreased OVA-mediated induction of Th2 cytokines in BALF and lung homogenates. Importantly, JEW-M449 delivered via the IN route reached the lung tissue more effectively and exerted superior anti-inflammatory effects in OVA-challenged mice than the IP-delivered JEW-M449. This study is the first to demonstrate the efficacy of directly delivering JEW-M449 anti-TCTP mAb into the respiratory tract to alleviate the asthma phenotype in a mouse model, thereby highlighting a potential delivery strategy for novel inhaled mAb therapeutics for human asthma.

Pharmacological and biochemical insights into lead-induced hepatotoxicity: Pathway interplay and the protective effects of arbutin via the oral and intraperitoneal routes in silico and in vivo.

INTRODUCTION: Lead acetate (PbAc), a hazardous heavy metal, poses significant threats to human health and the environment because of widespread industrial exposure. PbAc exposure leads to liver injury primarily through oxidative stress and the disruption of key regulatory pathways. Understanding these mechanisms and exploring protective agents are vital for mitigating PbAc-induced hepatotoxicity. Therefore, we aimed to investigate the molecular pathways implicated in PbAc-induced liver damage, focusing on Sirt-1, Nrf2 (HO-1, NQO1, and SOD), Akt-1/GSK3ß, m-TOR, and P53. Additionally, we aimed to assess the hepatoprotective effects of arbutin, which is administered orally and intraperitoneally, to determine the most effective delivery method. METHODOLOGY: In silico analyses were conducted to identify relevant protein networks associated with Sirt-1 and AKT-1/GSK-3B pathways. The pharmacodynamic properties of arbutin were examined, followed by molecular docking studies to elucidate its interactions with the selected protein network. In vivo preclinical studies were carried out on adult male rats randomly assigned to 6 different treatment groups, including PbAc exposure and PbAc exposure treated with arbutin either orally or intraperitoneally. RESULTS: PbAc exposure led to hepatic oxidative stress, as evidenced by elevated MDA levels and SIRT-1 inhibition, disrupting antioxidant pathways and activating antiautophagic and proapoptotic pathways, ultimately resulting in hepatocyte necrosis. Both oral and intraperitoneal arbutin administration effectively modifed these effects, with intraperitoneal delivery showing superior efficacy in mitigating PbAc-induced histological, immunological, and biochemical alterations. CONCLUSION: This study provides insights into the molecular mechanisms underlying PbAc-induced liver injury and highlights the hepatoprotective potential of arbutin. These findings suggest that arbutin, particularly when administered intraperitoneally, holds promise as a therapeutic agent for combating PbAc-induced hepatotoxicity.

Evaluation of micro-remnant niduses of arteriovenous malformations post-gamma knife radiosurgery by 3D-rotational angiography.

PURPOSE: Recent innovations in radiological imaging have enabled the detection of micro-remnant niduses of arteriovenous malformations (AVMs) after gamma knife radiosurgery (GKS), which have not been previously perceptible. Herein, we focus on the difficulty of evaluating micro-remnant AVMs after GKS that are hardly perceptible on conventional examinations and propose integrating follow-up three-dimensional rotational angiography (3D-RA) in the previous gamma plan as a solution. METHODS: We retrospectively searched NTT Medical Center Tokyo hospital database for patients with AVMs who underwent both two-dimensional digital subtraction angiography (2D-DSA) and 3D-RA as follow-up for GKS from February 2021 to January 2024. Patients with suspected nidus occlusion on the latest non-contrast-enhanced magnetic resonance angiography (NC-MRA) were included, and contrast-enhanced magnetic resonance angiography (CE-MRA), 2D-DSA, and 3D-RA were evaluated. RESULTS: Twelve patients with 13 AVM sites were defined as having complete nidus occlusion on upfront NC-MRA. On 2D-DSA, seven AVM sites showed the presence of slight remaining AVMs based on the detection of remnant drainage veins, however the nidus was not detected in three cases. Nevertheless, 3D-RA detected micro-remnant niduses in all seven AVM sites, and four patients underwent re-GKS. Nine patients with ten AVM sites also underwent CE-MRA, and six AVM sites were diagnosed with radiation-induced parenchymal injury. CONCLUSION: Importing the 3D-RA image into the treatment planning has the potential to be more helpful than NC-MRA or CE-MRA to detect micro-remnant AVMs and evaluate the true remnant volume, and may contribute to a more detailed treatment planning, thereby improving the results of GKS retreatment.

Synthesis of Carbon Dots from Peltophorum Pterocarpum Flowers for Selective Fluorescence Detection of Carbendazim.

In this study, carbon dots (CDs) were synthesized from Peltophorum pterocarpum flowers as the precursor material using the hydrothermal method. The fluorescence emission spectra of the resulting Peltophorum pterocarpum CDs (PP-CDs) exhibited excitation-independent behavior, showing the fluorescence emission peak at 410 nm when excited at 330 nm. This method is simple, rapid and well consistent with the green chemistry and sustainable analytical method development. The as-synthesized PP-CDs acted as a promising fluorescent probe for detecting carbendazim (CBZ) via aggregation-induced emission mechanism, showing a linear response to CBZ concentrations ranging from 1 to 30 µM, with a detection limit of 5.41 nM. This method was successfully applied to quantify CBZ in food samples, achieving excellent recoveries of 99% with a relative standard deviation (RSD) of less than 2%.

Development of irreversible pancreatic ductal change triggered by pancreatic duct stenting in chronic pancreatitis.

BACKGROUND AND AIM: Stent-induced ductal change is a complication of endoscopic pancreatic stent placement for chronic pancreatitis, potentially leading to irreversible changes that may contribute to pancreatic dysfunction. This study aimed to examine the long-term outcomes of stent-induced ductal change and evaluate factors that correlate with the development of irreversible ductal changes. METHODS: Between January 2008 and December 2022, 52/223 patients with chronic pancreatitis in whom an S-type plastic stent was successfully placed from the main papilla for duct stricture were detected with stent-induced ductal change on pancreatography at stent removal. We retrospectively investigated the clinical features of patients whose main pancreatic duct was reassessed by endoscopic pancreatography after >1 month without stent and whose residual stent-induced ductal change was irreversible. RESULTS: The patients with chronic pancreatitis with stent-induced ductal change (n = 28) (elevated change, 15; stricture change, 13) were evaluated using follow-up pancreatography. Eleven patients (39.3%) showed residual change associated with stent-induced ductal change, the degree of which was partial improvement, no change, and obstructive change in one, seven, and three patients, respectively. Stricture changes during stent removal and duration of stent placement that triggered ductal changes were significantly associated with the development of residual ductal changes. CONCLUSIONS: Irreversible stent-induced ductal change in patients with chronic pancreatitis was associated with stricture changes in the main pancreatic duct and continued plastic-stent placement. Careful evaluation of the pancreatic duct is required during plastic-stent placement. Early plastic-stent removal may result in an effective response to the development of stent-induced ductal change.

Clinical guidance for cannabidiol-associated hepatotoxicity: A narrative review.

There is increasing evidence that cannabidiol (CBD) use is associated with clinically significant liver enzyme (LE) elevations and drug-induced liver injury (DILI). The proportion of LE elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction. However, these potential adverse events are unknown to many clinicians and may be overlooked. The increasing use of CBD for both medical and non-medical use necessitates clear direction in the diagnosis and management of CBD-associated hepatotoxicity. To our knowledge, no such clinical guidance currently exists. For people presenting with elevated LEs, CBD use should be screened for and be considered in the differential diagnosis. This narrative review will provide clinicians with guidance in the prevention, detection, and management of CBD-related hepatotoxicity.

Deciphering the physiopathology of neurodevelopmental disorders using brain organoids.

Neurodevelopmental disorders (NDD) encompass a range of conditions marked by abnormal brain development in conjunction with impaired cognitive, emotional, and behavioural functions. Transgenic animal models, mainly rodents, traditionally served as key tools for deciphering the molecular mechanisms driving NDD physiopathology, and significantly contributed to the development of pharmacological interventions aimed at treating these disorders. However, the efficacy of these treatments in humans has proven to be limited, due in part to the intrinsic constraint of animal models to recapitulate the complex development and structure of the human brain but also to the phenotypic heterogeneity found between affected individuals. Significant advancements in the field of induced pluripotent stem cells (iPSC) offer a promising avenue for overcoming these challenges. Indeed, the development of advanced differentiation protocols for generating iPSC-derived brain organoids gives the unprecedented opportunity to explore the human neurodevelopment. This review provides an overview of how 3D brain organoids have been used to investigate various NDD (i.e., Fragile X syndrome, Rett syndrome, Angelman syndrome, microlissencephaly, Prader-Willi syndrome, Timothy Syndrome, tuberous sclerosis syndrome), and elucidate their pathophysiology. We also discuss the benefits and limitations of employing such innovative 3D models compared to animal models and 2D cell culture systems, in the realm of personalized medicine.

The effects of proton pump inhibitors during pregnancy on treatment of preeclampsia, and related outcomes: a systematic review and meta-analysis.

OBJECTIVE: This systematic review evaluated the available evidence of the effects of PPIs during pregnancy on preeclampsia and related maternal, fetal and neonatal outcomes. DATA SOURCES: Five electronic databases (MEDLINE, Embase, CINAHL, Cochrane CENTRAL, and Global Medicus Index) were searched on 17 November 2023. STUDY ELIGIBILITY CRITERIA: Randomized controlled trials involving pregnant women, using any class or dose of PPIs, were eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Meta-analysis was conducted for all outcomes of interest, with random-effects models. Results were presented as risk ratios or mean difference. Quality assessment was performed using the Risk of Bias 2 tool, and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessment was completed to evaluate the certainty of the evidence. The study was registered on PROSPERO (CRD42023423673). RESULTS: Our search identified 3,879 records, which were screened by two authors independently. Nine reports (describing eight trials) met our eligibility criteria, however six trials were ultimately excluded from our analysis as women were only given PPIs immediately prior to Cesarean section for acid aspiration prevention. The two trials included in the meta-analysis evaluated the treatment of 177 women with diagnosed preeclampsia. For the primary outcomes, moderate-certainty evidence showed there is likely no effect of the use of PPIs on risk of HELLP syndrome (RR 1.21, 95% CI 0.37 - 3.99, I²â€¯= 0%) or perinatal mortality (RR 0.81, 95% CI 0.36 - 1.79, I²â€¯= 0%), while there were insufficient data to meta-analyse all other primary outcomes, including eclampsia and neonatal mortality. No trials investigated PPIs for preventing preeclampsia. CONCLUSIONS: Given the limited outcome data we are uncertain of the effect of PPIs in women with preeclampsia. Further trials are required to determine what (if any) effects PPIs might have for preeclampsia prevention or treatment.

A Membrane-Anchoring Self-Assembling Peptide Allows Bioorthogonal Coupling of Type-I AIEgens for Pyroptosis-Induced Cancer Therapy.

Enrichment of photosensitizers (PSs) on cancer cell membranes via bioorthogonal reactions is considered to be a very promising therapeutic modality. However, azide-modified sugars-based metabolic labeling processes usually lack targeting and the labeling speed is relatively slow. Moreover, it has been rarely reported that membrane-anchoring pure type-I PSs can induce cancer cell pyroptosis. Here, we report an alkaline phosphatase (ALP) and cholecystokinin-2 receptor (CCK2R) dual-targeting peptide named DBCO-pYCCK6, which can selectively and rapidly self-assemble on cancer cell membrane, and then bioorthogonal enrich type-I aggregation-induced emission luminogens (AIEgen) PSs (SAIE-N3) on the cell membrane. Upon light irradiation, the membrane-anchoring SAIE-N3 could effectively generate type-I reactive oxygen species (ROS) to induce gasdermin E (GSDME)-mediated pyroptosis. In vivo experiments demonstrated that the bioorthogonal combination strategy of peptide and AIEgen PSs could significantly inhibit tumor growth, which is accompanied by CD8+ cytotoxic T cell infiltration. This work provides a novel self-assembly peptide-mediated bioorthogonal reaction strategy to bridge the supramolecular self-assembly and AIE field through strain-promoted azide-alkyne cycloaddition (SPAAC) and elucidates that pure type-I membrane-anchoring PSs can be used for cancer therapy via GSDME-mediated pyroptosis.

Silica-induced ROS in alveolar macrophages and its role on the formation of pulmonary fibrosis via polarizing macrophages into M2 phenotype: A review.

Alveolar Macrophages (AMs), the first line against the invasion of foreign invaders, play a predominant role in the pathogenesis of silicosis. Studies have shown that inhaled silica dust is recognized and engulfed by AMs, resulting in the production of large amounts of silica-induced ROS, including particle-derived Reactive Oxygen Species (ROS) and macrophage-derived ROS. These ROS change the microenvironment of the AMs where the macrophage phenotype is stimulated to swift from M0 to M1 and/or M2, and ultimately emerge as the M2 phenotype to trigger silicosis. This is a complex process accompanied by various molecular biological events. Unfortunately, the detailed processes and mechanisms have not been systematically described. In this review, we first systematically introduce the process of ROS induced by silica in AMs. Then describe the role and molecular mechanism of M2-type macrophage polarization caused by silica-induced ROS. Finally, we review the mechanism of pulmonary fibrosis induced by M2 polarized AMs. We conclude that silica-induced ROS initiate the fibrotic process of silicosis by inducing macrophage into M2 phenotype, and that targeted intervention of silica-induced ROS in AMs can reprogram the macrophage polarization and ameliorate the pathogenesis of silicosis.