Foveapeltis gen. nov., an unusual cleroid genus with large hypomeral cavities from mid-Cretaceous amber (Coleoptera: Cleroidea).

Beetles have a remote evolutionary history dating back to the Carboniferous, with Mesozoic fossils playing a pivotal role in elucidating the early evolution of extant families. Despite their exceptional preservation in amber, deciphering the systematic positions of Mesozoic trogossitid-like beetles remains challenging. Here, we describe and illustrate a new trogossitid-like lineage from mid-Cretaceous Kachin amber, Foveapeltis rutai Li, Kolibác, Liu & Cai, gen. et sp. nov. Foveapeltis stands out within the Cleroidea due to the presence of a significant large cavity on each hypomeron. While the exact phylogenetic placement of Foveapeltis remains uncertain, we offer a discussion on its potential affinity based on our constrained phylogenetic analyses.

[Modular pharmacology: research progress and development of analysis platform].

Based on the systematic deconstruction of multi-dimensional and multi-target biological networks, modular pharmacology explains the complex mechanism of diseases and the interactions of multi-target drugs. It has made progress in the fields of pathogenesis of disease, biological basis of disease and traditional Chinese medicine(TCM) syndrome, pharmacological mechanism of multi-target herbs, compatibility of formulas, and discovery of new drug of TCM compound. However, the complexity of multi-omics data and biological networks brings challenges to the modular deconstruction and analysis of the drug networks. Here, we constructed the "Computing Platform for Modular Pharmacology" online analysis system, which can implement the function of network construction, module identification, module discriminant analysis, hub-module analysis, intra-module and inter-module relationship analysis, and topological visualization of network based on quantitative expression profiles and protein-protein interaction(PPI) data. This tool provides a powerful tool for the research on complex diseases and multi-target drug mechanisms by means of modular pharmacology. The platform may have broad range of application in disease modular identification and correlation mechanism, interpretation of scientific principles of TCM, analysis of complex mechanisms of TCM and formulas, and discovery of multi-target drugs.

Recent advances in dietary polysaccharides from Allium species: Preparation, characterization, and bioactivity.

Allium plants, including garlic, onions, shallots, and leeks, belong to the Alliaceae family and are utilized as vegetable, medicinal, and ornamental plants. These plants are consumed both raw and cooked and are noted in traditional medicine for their antibacterial, antitumor, and diuretic properties. Allium plants are a rich source of polyphenols, organosulfur compounds, flavonoids, alkaloids, and polysaccharides, which contribute to their health benefits. As consumer interest in the association between diet and health grows, there is an increasing market demand for foods that promote health, particularly those rich in dietary fiber or non-starch polysaccharides. Allium polysaccharides (APS) have molecular weights of 1 × 103-1 × 106 Da containing small amounts of pectin, glucofructan, or glycoproteins and large amounts of fructans. APS, despite its complex structure, is one of the principal active components of Allium plants but is often overlooked, which restricts its practical application. This paper provides a comprehensive overview of the extraction and purification, structural and functional characteristics, bioactivities, structure-function relationships, and chemical modifications of APS, as well as the effects of APS processing and storage. Additionally, this paper outlines future research directions for APS, which will inform its development and application in the food, pharmaceutical, and cosmetic industries.

SWEET family transporters act as water conducting carrier proteins in plants.

Dedicated water channels are involved in the facilitated diffusion of water molecules across the cell membrane in plants. Transporter proteins are also known to transport water molecules along with substrates, however the molecular mechanism of water permeation is not well understood in plant transporters. Here, we show plant sugar transporters from the SWEET (Sugar Will Eventually be Exported Transporter) family act as water-conducting carrier proteins via a variety of passive and active mechanisms that allow diffusion of water molecules from one side of the membrane to the other. This study provides a molecular perspective on how plant membrane transporters act as water carrier proteins, a topic that has not been extensively explored in literature. Water permeation in membrane transporters could occur via four distinct mechanisms which form our hypothesis for water transport in SWEETs. These hypothesis are tested using molecular dynamics simulations of the outward-facing, occluded, and inward-facing state of AtSWEET1 to identify the water permeation pathways and the flux associated with them. The hydrophobic gates at the center of the transport tunnel act as a barrier that restricts water permeation. We have performed in silico single and double mutations of the hydrophobic gate residues to examine the changes in the water conductivity. Surprisingly, the double mutant allows the water permeation to the intracellular half of the membrane and forms a continuous water channel. These computational results are validated by experimentally examining the transport of hydrogen peroxide molecules by the AtSWEET family of transporters. We have also shown that the transport of hydrogen peroxide follows the similar mechanism as water transport in AtSWEET1. Finally, we conclude that similar water-conduction states are also present in other SWEET transporters due to the high sequence and structure conservation exhibited by this transporter family.

The treatment of high concentration wastewater in the natural gas processing industry.

The operation of the Cansolv tail gas treatment device in natural gas plants generates acidic and alkaline wastewater from the venturi unit and amine purification unit (APU), respectively. The APU wastewater is complex in composition and contains hard-to-degrade organic matter, which can adversely impact the normal functioning of the water treatment system. This study assesses the efficacy of three ozone-based advanced oxidation processes (ozone (O3), ozone/hydrogen peroxide (O3/H2O2), and ozone/Fenton (O3/Fenton)) for treating Cansolv wastewater, with chemical oxygen demand (COD) and total organic carbon (TOC) serving as indicators of organic degradation. The findings demonstrate that all three processes effectively eliminate coloration and reducible sulfur, with O3/Fenton exhibiting superior performance in removing organic substances. The treated wastewater has a clarified light-yellow appearance with residual COD levels at 43 mg L-1. Under the optimum Fenton oxidation conditions (initial pH 5, H2O2 dosage 97.8 mmol L-1, FeSO4·7H2O dosage 550 mg L-1), average TOC and COD removal rates reached 50% and 97%, respectively. After a treatment duration of 60 minutes, the wastewater demonstrated an enhanced membrane-specific flux, confirming the effectiveness of the O3/Fenton oxidation process in mitigating membrane fouling while ensuring the stable operation of the wastewater treatment system.

Low power density, high-efficiency reflective Raman system for polymer SERS substrates.

Surface-enhanced Raman spectroscopy (SERS) is a powerful measurement method in the chemical analysis field. It is much superior to bulk Raman owing to the enhancement of signal sensitivity from the SERS substrate. Nevertheless, the delicate SERS substrates are overpriced, which results in the difficulty of universal measurements. Accordingly, opting for a substrate made of polymer material based on the nanoimprint technique shows great potential for low-cost and high-performance SERS substrates. However, due to its low heat conductivity, the polymer's thermal properties may cause heat to concentrate on the incident spot and damage the nanostructures or analytes. In this article, we proposed a novel design of the Reflective Raman (RR) system to reduce the input power density and maintain high collection efficiency at the same time. The proposed RR system was directly compared with a traditional micro Raman (µ-Raman) system and demonstrated its outstanding performance for low damage threshold analytes and SERS substrates.

Lethal pulmonary thromboembolism in mice induced by intravenous human umbilical cord mesenchymal stem cell-derived large extracellular vesicles in a dose- and tissue factor-dependent manner.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have obvious advantages over MSC therapy. But the strong procoagulant properties of MSC-EVs pose a potential risk of thromboembolism, an issue that remains insufficiently explored. In this study, we systematically investigated the procoagulant activity of large EVs derived from human umbilical cord MSCs (UC-EVs) both in vitro and in vivo. UC-EVs were isolated from cell culture supernatants. Mice were injected with UC-EVs (0.125, 0.25, 0.5, 1, 2, 4 µg/g body weight) in 100 µL PBS via the tail vein. Behavior and mortality were monitored for 30 min after injection. We showed that these UC-EVs activated coagulation in a dose- and tissue factor-dependent manner. UC-EVs-induced coagulation in vitro could be inhibited by addition of tissue factor pathway inhibitor. Notably, intravenous administration of high doses of the UC-EVs (1 µg/g body weight or higher) led to rapid mortality due to multiple thrombus formations in lung tissue, platelets, and fibrinogen depletion, and prolonged prothrombin and activated partial thromboplastin times. Importantly, we demonstrated that pulmonary thromboembolism induced by the UC-EVs could be prevented by either reducing the infusion rate or by pre-injection of heparin, a known anticoagulant. In conclusion, this study elucidates the procoagulant characteristics and mechanisms of large UC-EVs, details the associated coagulation risk during intravenous delivery, sets a safe upper limit for intravenous dose, and offers effective strategies to prevent such mortal risks when high doses of large UC-EVs are needed for optimal therapeutic effects, with implications for the development and application of large UC-EV-based as well as other MSC-EV-based therapies.

Value of sonoelastography for diagnosis of breast non-mass lesions and comparison with BI-RADS: A systematic review and meta-analysis.

BACKGROUND: Not all the breast lesions were mass-like, some were non-mass-like at ultrasonography. In these lesions, conventional ultrasonography had a high sensitivity but a low specificity. Sonoelastography can evaluate tissue stiffness to differentiate malignant masses from benign ones. Then what about the non-mass lesions? The aim of this study was to evaluate the current accuracy of sonoelastography in the breast non-mass lesions and compare the results with those of the American College of Radiology breast Imaging-Reporting and Data System (BI-RADS). METHODS: An independent literature search of English medical databases, including PubMed, Web of Science, Embase & MEDLINE (Embase.com) and Cochrane Library, was performed by 2 researchers. The accuracy of sonoelastography was calculated and compared with those of BI-RADS. RESULTS: Fourteen relevant studies including 1058 breast non-mass lesions were included. Sonoelastography showed a pooled sensitivity of 0.74 (95% CI: 0.70-0.78), specificity of 0.89 (95% CI: 0.85-0.91), diagnostic odds ratio (DOR) of 25.22 (95% CI: 17.71-35.92), and an area under the curve of 0.9042. Eight articles included both sonoelastography and BI-RADS. The pooled sensitivity, specificity, DOR and AUC were 0.69 versus 0.91 (P < .01), 0.90 versus 0.68 (P < .01), 19.65 versus 29.34 (P > .05), and 0.8685 versus 0.9327 (P > .05), respectively. CONCLUSIONS: Sonoelastography has a higher specificity and a lower sensitivity for differential diagnosis between malignant and benign breast non-mass lesions compared with BI-RADS, although there were no differences in AUC between them.

Subcostal uniportal robotic anatomic lung resection: A pilot trial.

Objective: Robot-assisted thoracoscopic surgery typically necessitates the use of multiple ports. The new single-port robotic system (da Vinci SP system) platform is designed to perform uniportal surgery. The purpose of this clinical trial is to evaluate the feasibility, efficacy, and safety of the da Vinci SP system when used for anatomical lung resection. Methods: Patients diagnosed with clinical stage I lung cancer requiring anatomical lung resections were considered eligible for this trial. The primary outcome measure was the rate of conversion, whereas the secondary objective focused on assessing the incidence of perioperative complications. Results: The study included 35 patients with a median age of 63 years (range, 48-74 years). Of these, 30 underwent lobectomy and 5 received segmentectomy. All surgeries were successfully performed using a subcostal approach, except for 1 patient, who required a thoracotomy conversion due to bleeding (conversion rate: 2.9%). The median docking time was 2 minutes (range, 1-8 minutes). For the 34 patients who completed uniportal surgery, the median total operating time was 194 minutes (range, 63-405 minutes), whereas the console time was 153 minutes (range, 93-267 minutes). The median number of harvested nodes was 13 (range, 5-37), while the median number of nodal stations was 6 (rang, 4-8). There were no in-hospital fatalities, and the median postoperative stay was 3 days (range, 2-12 days). Conclusions: This study demonstrates the feasibility and safety of using the da Vinci SP system for anatomical lung resection through a subcostal approach. ClinicalTrialsgov identifier: NCT05535712.

Bidirectional causality between idiopathic sudden sensorineural hearing loss and depression: a Mendelian randomization study.

Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) is a sudden onset, unexplained sensorineural hearing loss. Depression is a common mental disorder and a leading cause of disability. Here, We used a two-sample Mendelian randomization approach using pooled statistics from genome-wide association studies of ISSHL (1491 cases, 196,592 controls) and depression (23,424 cases, 192,220 controls) in European populations. This study investigated the bidirectional relationship between single nucleotide polymorphisms associated with depression and ISSHL using inverse variance weighting.Additional sensitivity analyses, such as Mendelian randomization-Egger (MR-Egger), weighted median estimates, and leave-one-out analysis, were performed to assess the reliability of the findings. Significant causal association between genetic susceptibility to ISSHL and depression in a random-effects IVW approach (OR = 1.037, 95% CI = 1.004-1.072, P = 0.030). In contrast, genetic depression was not risk factors for ISSHL (OR = 1.134, 95% CI = 0.871-1.475, P = 0.350). After validation by different MR methods and the sensitivity analysis, all of the above results are consistent. The evidence we have gathered suggests a causal relationship between ISSHL and depression. The presence of the former induces or further exacerbates the latter, whereas a similar situation does not exist when the latter is an influencing factor.

Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

Targeting gut microbiota for immunotherapy of diseases.

With advances in next-generation sequencing technology, there is growing evidence that the gut microbiome plays a key role in the host's innate and adaptive immune system. Gut microbes and their metabolites directly or indirectly regulate host immune cells. Crucially, dysregulation of the gut microbiota is often associated with many immune system diseases. In turn, microbes modulate disease immunotherapy. Data from preclinical to clinical studies suggest that the gut microbiota may influence the effectiveness of tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs). In addition, the most critical issue now is a COVID-19 vaccine that generates strong and durable immunity. A growing number of clinical studies confirm the potential of gut microbes to enhance the efficacy of COVID-19 vaccines. However, it is still unclear how gut bacteria interact with immune cells and what treatments are based on gut microbes. Here, we outline recent advances in the effects and mechanisms of the gut microbiota and its metabolites (tryptophan metabolites, bile acids, short-chain fatty acids, and inosine) on different immune cells (dendritic cells, CD4+T cells, and macrophages). It also highlights innovative intervention strategies and clinical trials of microbiota-based checkpoint blocking therapies for tumor immunity, and ongoing efforts to maintain the long-term immunogenicity of COVID-19 vaccines. Finally, the challenges to be overcome in this area are discussed. These provide an important basis for further research and clinical translation of gut microbiota.

[Experimental evaluation of the efficacy of tissue-engineered constructs in the treatment of limbal stem cell deficiency]. / Eksperimental'naya otsenka effektivnosti primeneniya tkaneinzhenernoi konstruktsii v lechenii limbal'noi nedostatochnosti.

Limbal stem cell deficiency (LSCD) is one of the leading factors negatively affecting the success of keratoplasty, and its treatment remains an urgent problem in ophthalmology. With the development of regenerative medicine, one of the promising approaches is the transplantation of tissue-engineered constructs from cultured limbal stem cells (LSCs) in biopolymer carriers. PURPOSE: This study was conducted to develop an experimental model of LSCD and evaluate the effectiveness of transplantation of a tissue-engineered construct consisting of cultured cells containing a population of LSCs and a collagen carrier. MATERIAL AND METHODS: The study was performed on 12 rabbits and included several stages. At the first stage, the physiological effects of collagen matrix implantation into the limbal zone were studied. At the second stage, tissue-engineered constructs consisting of LSCs on a collagen matrix were formed and their effect on the regeneration processes in the experimental LSCD model was analyzed. The animals were divided into 2 groups: surgical treatment (transplantation of the tissue-engineered construct) was used in the experimental group, and conservative treatment was used in the control group. Slit-lamp biomicroscopy with photo-registration, fluorescein corneal staining, optical coherence tomography of the anterior segment of the eye, and impression cytology were used to assess the results. RESULTS: No side reactions were observed after implantation of the collagen matrix into the limbal zone. One month after surgical treatment of the LSCD model in the experimental group, complete epithelization with minor manifestations of epitheliopathy was observed. In the control group, erosion of the corneal epithelium was noted. The time of corneal epithelization in the experimental and control groups was 9.2±2.95 and 46.20±12.07 days, respectively (p=0.139). According to the data of impression cytology, in the experimental group there were no goblet cells in the central part of the cornea, which indicates the restoration of corneal type epithelial cells, in contrast to the control group. CONCLUSION: Transplantation of a tissue-engineered construct from cultured limbal cells on a collagen membrane should be considered as a promising method for the treatment of limbal stem cell deficiency.

Single-Port Robotic Trans-Subxiphoid Surgery for Anterior Mediastinal Disease: A Pilot Trial.

OBJECTIVE: In recent years, there has been an increasing focus on minimally invasive mediastinal surgery using a trans-subxiphoid single-port thoracoscopic approach. Despite its potential advantages, the widespread adoption of this method has been hindered by the intricate surgical maneuvers required within the confined retrosternal space. Robotic surgery offers the potential to overcome the limitations inherent in the thoracoscopic technique. METHODS: This was a clinical trial (NCT05455840) to evaluate the feasibility and safety of utilizing the da Vinci® SP system (Intuitive Surgical, Sunnyvale, CA, USA) for trans-subxiphoid single-port surgery in patients with anterior mediastinal disease. The primary endpoints encompassed conversion rates and the secondary endpoints included the occurrence of perioperative complications. RESULTS: Between August 2022 and April 2023, a total of 15 patients (7 men and 8 women; median age = 56 years, interquartile range [IQR]: 49 to 65 years) underwent trans-subxiphoid robotic surgery using da Vinci SP platform for maximal thymectomy (n = 2) or removal of anterior mediastinal masses (n = 13). All surgical procedures were carried out with success, with no need for conversion to open surgery or the creation of additional ports. The median docking time was 2 min (IQR: 1 to 4 min), while the console time had a median of 152 min (IQR: 95 to 191 min). There were no postoperative complications and patients experienced a median postoperative hospital stay of 2 days with no unplanned 30-day readmission. CONCLUSIONS: This study shows that trans-subxiphoid single-port robotic surgery employing the da Vinci SP system in patients with anterior mediastinal disease is clinically viable with acceptable safety and short-term outcomes.

A study on the application of radiomics based on cardiac MR non-enhanced cine sequence in the early diagnosis of hypertensive heart disease.

BACKGROUND: The prevalence of hypertensive heart disease (HHD) is high and there is currently no easy way to detect early HHD. Explore the application of radiomics using cardiac magnetic resonance (CMR) non-enhanced cine sequences in diagnosing HHD and latent cardiac changes caused by hypertension. METHODS: 132 patients who underwent CMR scanning were divided into groups: HHD (42), hypertension with normal cardiac structure and function (HWN) group (46), and normal control (NOR) group (44). Myocardial regions of the end-diastolic (ED) and end-systolic (ES) phases of the CMR short-axis cine sequence images were segmented into regions of interest (ROI). Three feature subsets (ED, ES, and ED combined with ES) were established after radiomic least absolute shrinkage and selection operator feature selection. Nine radiomic models were built using random forest (RF), support vector machine (SVM), and naive Bayes. Model performance was analyzed using receiver operating characteristic curves, and metrics like accuracy, area under the curve (AUC), precision, recall, and specificity. RESULTS: The feature subsets included first-order, shape, and texture features. SVM of ED combined with ES achieved the highest accuracy (0.833), with a macro-average AUC of 0.941. AUCs for HHD, HWN, and NOR identification were 0.967, 0.876, and 0.963, respectively. Precisions were 0.972, 0.740, and 0.826; recalls were 0.833, 0.804, and 0.863, respectively; and specificities were 0.989, 0.863, and 0.909, respectively. CONCLUSIONS: Radiomics technology using CMR non-enhanced cine sequences can detect early cardiac changes due to hypertension. It holds promise for future use in screening for latent cardiac damage in early HHD.

Biomaterials science and surface engineering strategies for dental peri-implantitis management.

Peri-implantitis is a bacterial infection that causes soft tissue inflammatory lesions and alveolar bone resorption, ultimately resulting in implant failure. Dental implants for clinical use barely have antibacterial properties, and bacterial colonization and biofilm formation on the dental implants are major causes of peri-implantitis. Treatment strategies such as mechanical debridement and antibiotic therapy have been used to remove dental plaque. However, it is particularly important to prevent the occurrence of peri-implantitis rather than treatment. Therefore, the current research spot has focused on improving the antibacterial properties of dental implants, such as the construction of specific micro-nano surface texture, the introduction of diverse functional coatings, or the application of materials with intrinsic antibacterial properties. The aforementioned antibacterial surfaces can be incorporated with bioactive molecules, metallic nanoparticles, or other functional components to further enhance the osteogenic properties and accelerate the healing process. In this review, we summarize the recent developments in biomaterial science and the modification strategies applied to dental implants to inhibit biofilm formation and facilitate bone-implant integration. Furthermore, we summarized the obstacles existing in the process of laboratory research to reach the clinic products, and propose corresponding directions for future developments and research perspectives, so that to provide insights into the rational design and construction of dental implants with the aim to balance antibacterial efficacy, biological safety, and osteogenic property.

In vitro simulated digestion and fermentation characteristics of pectic polysaccharides from fresh passion fruit (Passiflora edulis f. flavicarpa L.) peel.

In this study, two pectic polysaccharides (PFP-T and PFP-UM) were extracted from fresh passion fruit peels using three-phase partitioning (TPP) and sequential ultrasound-microwave-assisted TPP methods, respectively, and their effects on the in vitro gastrointestinal digestion and fecal fermentation characteristics were examined. The results indicate that gastrointestinal digestion has a minimal effect on the physicochemical and structural characteristics of PFP-T and PFP-UM. However, during in vitro fecal fermentation, both undigested PFP-T and PFP-UM are significantly degraded and utilized by intestinal microorganisms, showing increased the total relative abundance of Firmicutes and Bacteroidota in the intestinal flora. Notably, compared with PFP-UM, PFP-T better promoted the reproduction of beneficial bacteria such as Prevotella, Megasphaera and Dialister, while suppressed the growth of harmful genera including Escherichia-Shigella, producing higher content of short-chain fatty acids. Therefore, our findings suggest that PFP-T derived from passion fruit peel has potential as a dietary supplement for promoting intestinal health.

[Methods for research on structures and functions of traditional Chinese medicine proteins].

Traditional Chinese medicine proteins(TCMPs) not only have nutritional values and biological activities but also serve as key enzymes in the synthesis of pharmacodynamic components in traditional Chinese medicines. They play a role in the synthesis of pharmacodynamic components by regulating biosynthesis and selective synthesis pathways and controlling drug quality and stability. The recent years have witnessed great progress in the research on the structures and functions of proteins using various methods and technologies. However, the research on the structures and functions of TCMPs lags behind. Therefore, it is urgent to study the structures and functions of TCMPs using modern means to promote the discovery of innovative drugs based on TCMPs and clarify the synthesis pathways of pharmacodynamic components. This study introduces the latest techniques for studying protein structures and functions, including spectroscopy, mass spectrometry, nuclear magnetic resonance, X-ray crystal diffraction, microscopy, and structure prediction. Furthermore, this paper introduces the methods for protein functional studies, including liquid chromatography-mass spectrometry, co-immunoprecipitation, yeast two-hybrid, and pull-down assay. By systematically reviewing these techniques and methods, this paper provides technical references for the structural identification and functional studies of TCMPs, with the aim of promoting the in-depth exploration of the structures and functions of TCMPs.

Wogonin ameliorates ER stress-associated inflammatory response, apoptotic death and renal fibrosis in a unilateral ureteral obstruction mouse model.

Wogonin, a vital bioactive compound extracted from the medicinal plant, Scutellaria baicalensis, has been wildly used for its potential in mitigating the progression of chronic diseases. Chronic kidney disease (CKD) represents a significant global health challenge due to its high prevalence, morbidity and mortality rates, and associated complications. This study aimed to assess the potential of wogonin in attenuating renal fibrosis and to elucidate the underlying molecular mechanisms using a unilateral ureteral obstruction (UUO) mouse model as a CKD mimic. Male mice, 8 weeks old, underwent orally administrated of either 50 mg/kg/day of wogonin or positive control of 5 mg/kg/day candesartan following UUO surgery. NRK52E cells were exposed to tumor growth factors-beta (TGF-ß) to evaluate the anti-fibrotic effects of wogonin. The results demonstrated that wogonin treatment effectively attenuated TGF-ß-induced fibrosis markers in NRK-52E cells. Additionally, administration of wogonin significantly improved histopathological alterations and downregulated the expression of pro-fibrotic factors (Fibronectin, α-smooth muscle actin, Collagen IV, E-cadherin, and TGF-ß), oxidative stress markers (Catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), inflammatory molecules (Cyclooxygenase-2 and TNF-α), and the infiltration of neutrophils and macrophages in UUO mice. Furthermore, wogonin treatment mitigated endoplasmic reticulum (ER) stress-associated molecular markers (GRP78, GRP94, ATF4, CHOP, and the caspase cascade) and suppressed apoptosis. The findings indicate that wogonin treatment ameliorates key fibrotic aspects of CKD by attenuating ER stress-related apoptosis, inflammation, and oxidative stress, suggesting its potential as a future therapeutic target.