Cardiovascular disease is a significant health concern worldwide, and varied effective treatment and prevention methods have been developed. Among these, tailored biomaterials-based strategies such as stents, scaffolds, patches, and drug delivery systems have emerged as a promising avenue. These devices are designed to match the mechanical and biological mechanisms of the cardiovascular system, ensuring optimal performance and compatibility. By effectively treating or preventing cardiovascular diseases, these devices have the potential to improve patient health outcomes significantly. They can restore blood flow by addressing blocked arteries and regenerate damaged cardiac tissue by delivering bioactive agents or cells directly to the affected area in a targeted, sustained, and controllable manner. Therefore, the objective of this article is to summarize the available evidence on these tailored biomaterial-based tunable cardiovascular devices. This knowledge can help to transform cardiovascular medicine for the treatment or prevention of cardiovascular disease and restore cardiac function to improve patients' quality of life.

As advances in RNA modification research progress, the significance of 5-methylcytosine (m5C) modification is being increasingly acknowledged. m5C undergoes modification by the methyltransferase NOP2/Sun domain (NSUN) family/DNA methyltransferase (DNMT) family (writer) and is removed by demethylases (eraser), including the ten-eleven translocation (TET) family and Alkb homolog 1 (ALKBH1). Moreover, m5C interacts with RNA-binding proteins (reader), such as Y-box-binding protein 1 (YBX1) and Aly/REF export factor (ALYREF). Expanding on this structural framework, m5C modification possesses the capacity to regulate various physiological and pathological processes. Recent studies indicate that m5C plays a pivotal regulatory role in the central nervous system, and its dysregulation may correlate with the onset and progression of various central nervous system diseases. In this review, we summarize recent research on m5C components and delve into the potential mechanisms of m5C involvement in central nervous system disorders, such as Alzheimer's disease, brain tumors, epilepsy, and stroke.

Background: Alzheimer's disease results in neurodegeneration and is characterized by an accumulation of abnormal neuritic lesions and intracellular aggregates of hyperphosphorylated Tau proteins in the cerebrum. That leads to progressive decline in memory, thinking, and learning skills. Oxidative stress has been shown to play a significant role in the pathogenesis of Alzheimer's disease. Antioxidants are identified as part of therapeutic strategy to prevent or reduce the disease. Idebenone is a synthetic analogue of coenzyme Q₁₀ with potent antioxidant properties, originally developed for the treatment of Alzheimer's disease and other cognitive disorders. After oral administration idebenone undergoes excessive first-pass metabolism and has a very low bioavailability of only about 1%. The use of an alternative route of administration such as the nasal and its incorporation into a novel carrier (nanocomposite microspheres) will eliminate the problems associated with reduced absorption, stability, and rapid biotransformation and will increase the opportunity for idebenone to realize its therapeutic potential in Alzheimer's disease.

Methods: Idebenone-loaded nanocomposite microspheres were obtained by spray drying. The structures were characterized using laser diffraction, scanning electron microscopy, high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The ability of nanocomposite microspheres to bind human serum albumin was investigated by fluorescence spectroscopy. The mucoadhesive properties of the carrier were also determined.

Results: Bioadhesive nanocomposite microparticles with spherical shape, smooth surface, size of 7.37 ± 2.4 μm, and with high production yield, good drug entrapment efficiency, and loading values were obtained. Infrared spectra demonstrated no chemical interactions between idebenone and structure-forming polymers. The ability of particles to bind to human serum albumin depends on their drug loading.

Conclusions: Nanocomposite microspheres were developed as the novel delivery system of idebenone for target nose-to-brain delivery. The obtained carrier may increase the therapeutic potential of idebenone by providing higher concentrations in brain tissue and reducing systemic exposure and side effects.

Background: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, and even lifelong disability. This study was to explore the effect of riboflavin (RF) on neurological rehabilitation and functional recovery after TBI.

Methods: The rat models of TBI were constructed by treating rats with controlled cortical impact (CCI). By treating TBI rats with RF, we investigated whether the administration of RF would affect the sensorimotor function and cognitive ability recovery through adhesive removal test, modified neurological severity score (mNSS), corner test, wire-grip test and the Morris water maze. The effects of RF on lesion volume and water content were investigated using hematoxylin and eosin (H&E) staining and wet-dry method. The Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to demonstrate the effect of RF on neural apoptosis. Inflammation-related cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RF on neuroinflammation. The impact of RF on oxidative stress was assessed by measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and the platelet endothelial cell adhesion molecule-1 (CD31) staining for observing vessel density, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for measuring vascular endothelial growth factor (VEGF) mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis.

Results: The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability (p < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress (p < 0.05). Finally, RF increased vessel density (p < 0.01) and VEGF levels (p < 0.01) in brain tissues after TBI, promoting angiogenesis.

Conclusion: RF benefits neurological rehabilitation after TBI by promoting neurological function recovery, ameliorating the pathogenesis after TBI, and facilitating brain vascular remodeling. These findings provide a novel mechanism for RF treating pediatric TBI.

Background: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI.

Methods: A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation in vitro. VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments.

Results: Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1β, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis.

Conclusion: Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.

Background: Atrial fibrillation (AF) is the most common type of arrhythmia. Heart rate variability (HRV) may be associated with AF risk. The aim of this study was to test HRV indices and arrhythmias as predictors of paroxysmal AF based on 24-hour dynamic electrocardiogram recordings of patients.

Methods: A total of 199 patients with paroxysmal AF (AF group) and 204 elderly volunteers over 60 years old (Control group) who underwent a 24-hour dynamic electrocardiogram from August 2022 to March 2023 were included. Time-domain indices, frequency-domain indices, and arrhythmia data of the two groups were classified and measured. Binary logistic regression analysis was performed on variables with significant differences to identify independent risk factors. A nomogram prediction model was established, and the sum of individual scores of each variable was calculated.

Results: Gender, age, body mass index and low-density lipoprotein (LDL) did not differ significantly between AF and Control groups (p > 0.05), whereas significant group differences were found for smoking, hypertension, diabetes, and high-density lipoprotein (HDL) (p < 0.05). The standard deviation of all normal to normal (NN) R-R intervals (SDNN), standard deviation of 5-minute average NN intervals (SDANN), root mean square of successive NN interval differences (rMSSD), 50 ms from the preceding interval (pNN50), low-frequency/high-frequency (LF/HF), LF, premature atrial contractions (PACs), atrial tachycardia (AT), T-wave index, and ST-segment index differed significantly between the two groups. Logistic regression analysis identified rMSSD, PACs, and AT as independent predictors of AF. For each unit increase in rMSSD and PACs, the odds of developing AF increased by 1.0357 and 1.0005 times, respectively. For each unit increase in AT, the odds of developing AF decreased by 0.9976 times. The total score of the nomogram prediction model ranged from 0 to 110.

Conclusion: The autonomic nervous system (ANS) plays a pivotal role in the occurrence and development of AF. The individualized nomogram prediction model of AF occurrence contributes to the early identification of high-risk patients with AF.

Background: Idiopathic pulmonary fibrosis (IPF) is a long-term, progressive, and irreversible pulmonary interstitial disease. The activation of Smad family member 2 (Smad2) and Smad3 transcription factors by transforming growth factor β-1 (TGF-β1) is a critical event in the pathogenesis of IPF. However, there is still a lack of understanding regarding the molecular mechanisms governing Smad2 and Smad3 proteins. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that plays a vital role in regulating protein stability within cells. However, its regulation of the TGF-β signaling pathway and its significance in IPF remain undiscovered. This study aims to clarify the function of USP7 in the TGF-β signaling pathway, while simultaneously exploring the specific molecular mechanisms involved. Additionally, this study seeks to evaluate the therapeutic potential of targeted USP7 inhibitors in IPF, thereby providing novel insights for the diagnosis and management of IPF.

Methods: We first detected the expression of USP7 in lung tissues of mice with Bleomycin (BLM)-induced pulmonary fibrosis and in Beas-2B cells treated with or without TGF-β1 through Western blot analysis. Subsequently, we explored the influence of USP7 on fibrotic processes and the TGF-β1 signaling pathway, utilizing in vitro and in vivo studies. Finally, we assessed the effectiveness of USP7-specific inhibitors in an IPF murine model.

Results: In the present study, USP7 was found to de-ubiquitinate Smad2 and Smad3, consequently increasing their stability and promoting the TGF-β1-induced production of profibrotic proteins including α-smooth muscle actin (α-SMA) and fibronectin 1 (FN-1). Inhibition or knockdown of USP7 resulted in decreased levels of Smad2 and Smad3 proteins, leading to reduced expression of FN-1, Collagen Type I Alpha 1 Chain (Col1A1), and α-SMA induced by TGF-β1 in human pulmonary epithelial cells. These findings demonstrate that overexpression of USP7 reduces Smad2/3 ubiquitination, whereas inhibition or knockdown of USP7 enhances their ubiquitination. USP7 is abundantly expressed in IPF lungs. The expressions of USP7, Smad2, and Smad3 were upregulated in bleomycin-induced lung injury. The USP7 inhibitor P22077 reduced the expression of FN-1 and type I collagen as well as Smad2/3 and collagen deposition in lung tissue in a model of pulmonary fibrosis induced by bleomycin.

Conclusions: This study demonstrates that USP7 promotes TGF-β1 signaling by stabilizing Smad2 and Smad3. The contribution of USP7 to the progression of IPF indicates it may be a viable treatment target.

Background: Tumor necrosis factor alpha induced protein 3 (TNFAIP3) is reportedly to have significant implications for autophagy regulation in various cancers. The current study aimed to decipher the role and mechanism of TNFAIP3 in diffuse large B-cell lymphoma (DLBCL) by modulating autophagy.

Methods: Information pertaining to the differential expression and prognostic role of TNFAIP3 in DLBCL was gleaned from the Gene Expression Omnibus (GEO) database. The TNFAIP3 expression levels in human DLBCL cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and colony formation assays were employed to determine cell proliferation. Transwell assay and flow cytometry were applied to detect cell migration and apoptosis, respectively. Immunofluorescence and transmission electron microscope were used for the assessment of cell autophagy. The levels of apoptotic markers (caspase-3, cleaved-caspase-3, Bcl-2 Associated X (Bax), and B cell lymphoma-2 (Bcl-2)), autophagy indicators (the ratio of microtubule-associated proteins 1A/1B light chain 3 II and I (LC3II/LC3I), Sequestosome (p62)), and pathway proteins (toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), Transcription Factor NF-Kappa-B P65 Subunit (p65), and phosphorylated-p65 (p-p65)) were assessed via Western blotting. Immunohistochemistry was employed to detect Ki67 expression in tumor tissues.

Results: TNFAIP3 expression in DLBCL samples was downregulated, correlating with poor prognosis. TNFAIP3 expression was also downregulated in DLBCL cells. It was found that TNFAIP3 impeded cell proliferation and migration, and enhanced apoptosis of OCI-LY3 cells. Intervention with autophagy inhibitor 3-methyladenine (3-MA) markedly reversed apoptosis of OCI-LY3 cells induced by TNFAIP3. Besides, TNFAIP3 induced autophagy via modulating the TLR4/MyD88/nuclear factor kappa B (NF-κB) signaling pathway. In vivo experiments showed that TNFAIP3 expression in DLBCL was downregulated, and upregulation of TNFAIP3 could inhibit tumor growth.

Conclusion: TNFAIP3 inhibits DLBCL progression by inducing TLR4/MyD88/NF-κB pathway-mediated autophagy.

Background: Aciclovir, often known as acyclovir, is a nucleoside analog that exhibits antiviral activity in vitro against human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), varicella-zoster virus (VZV), and herpes simplex virus (HSV). Valacyclovir is an amino acid ester prodrug of acyclovir. We examined valacyclovir, which is also an anti-viral agent, for its effects on inflammation.

Methods: Mammalian Macrophages were activated by lipopolysaccharide (LPS) in the presence of a concentration range of Valacyclovir. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-12p40 enzyme-linked immunosorbent assay (ELISA) was performed to measure the production levels of these pro-inflammatory cytokines.

Results: Our results suggest that Valacyclovir had anti-inflammatory activity on the LPS-activated mammalian macrophages.

Conclusion: Valacyclovir has the potential to be utilized in the clinical setting as an anti-viral drug molecule with anti-inflammatory properties. Future studies are needed to further confirm its activities on different immune system cell types.

Background: Osteosarcoma (OS) is commonly recognized as a malignant cancer originating from bone-forming mesenchymal stem cells, comprising approximately 20% of sarcomas. Baicalin, a bioactive flavonoid glycoside isolated from Scutellaria baicalensis, has been demonstrated to possess potent anti-inflammatory and neuroprotective properties.

Objective: To explore the potential mechanisms through which baicalin exerts anti-osteosarcoma effects and facilitates osteogenesis in vitro.

Methods: Cell Counting Kit-8 (CCK-8), scratch assay, and transwell assay were employed to assess the effects of baicalin at varying concentrations (20, 40, and 80 μM) on U2OS cell proliferation, invasion, and migration, respectively. Western blot and qRT-PCR analyses were conducted to evaluate the influence of baicalin on the osteogenic potential of OS cells by examining osteoblast markers such as osteocalcin (OCN), osteopontin (OPN), and runt-related transcription factor 2 (RUNX2), as well as the osteoclast marker—receptor activator of nuclear factor kappa B ligand (RANKL). Additionally, the impact of baicalin on epithelial-mesenchymal transition (EMT) markers (N-cadherin, E-cadherin, Vimentin) and proteins related to the Nuclear factor κB (NF-κB) signaling pathway (p-p65, p-IκBα, p65, IκBα) in OS cells was evaluated via western blot analysis. The activity and mineralization capacity of Alkaline Phosphatase (ALP) in baicalin-treated cells were examined through ALP staining and Alizarin Red S (ARS) staining.

Results: Baicalin exhibited significant suppression of OS cell U2OS invasion (p < 0.01), migration (p < 0.01), and proliferation (p < 0.05) at various concentrations. Additionally, baicalin treatment notably increased the E-cadherin protein level, while decreasing the expression levels of Vimentin and N-cadherin proteins (p < 0.01), thus promoting EMT. Following baicalin treatment, there was a marked elevation in the protein and mRNA expression levels of RUNX2, OPN, and OCN, while the expression level of RANKL protein was reduced (p < 0.05), indicating enhanced osteogenic differentiation. The groups treated with baicalin exhibited higher ALP activity and mineralization ability (p < 0.01). Moreover, baicalin treatment significantly reduced the expression levels of p-IκBα and p-p65 proteins, as well as the ratios of p-IκBα/IκBα and p-p65/p65 (p < 0.01). These effects of baicalin were concentration-dependent, with higher concentrations yielding stronger effects.

Conclusion: In vitro, baicalin demonstrates anti-OS effects and facilitates osteogenic differentiation, potentially by inhibiting NF-κB pathway activity.

Background: Periodontitis is the leading cause of tooth loss and can exacerbate various systemic inflammatory conditions. Periodontal ligament stem cells (PDLSCs) stand out as prominent and favorable candidates for promoting periodontal tissue regeneration. This study aimed to investigate whether the protease-activated receptor type 1 (PAR1) can mitigate the sodium butyrate (NaB)-induced PDLSCs osteogenesis inhibition and unravel the underlying mechanism.

Methods: Public datasets from the Gene Expression Omnibus (GEO) were utilized to analyze differentially expressed genes (DEGs) in periodontitis and subsequent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. PDLSCs were cultured normally in control medium (CM) as the negative control or in osteogenic medium (OM) to induce osteogenesis. PAR1 was either activated or suppressed using a selective agonist or antagonist (OM+agonist and OM+antagonist). The evaluation of PDLSCs osteogenesis was based on the levels of osteogenesis-related markers, including runt-related transcription factor 2 (RUNX2), osterix (OSX), osteocalcin (OCN), and osteopontin (OPN), alkaline phosphatase (ALP) activity, and calcium concentration. Additionally, cell proliferation and osteogenic differentiation were measured through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Alizarin Red Staining. To determine the PAR1 targeting the limb development membrane protein 1 (LMBR1)/bone morphogenetic protein (BMP) pathway, LMBR1 was upregulated through cell transfection and BMP2 was inhibited using the selective inhibitor Noggin protein. Finally, NaB was introduced into PDLSCs to investigate the effect on NaB-induced inhibition of PDLSCs osteogenesis.

Results: PAR1, RUNX2, OSX, OCN, OPN, proliferation, ALP activity, calcium concentration, osteogenic differentiation, BMP2, and BMP4 exhibited significant increases in PDLSCs cultured in OM (p < 0.01). These parameters were further elevated by PAR1 agonist and conversely reduced by PAR1 antagonist (p < 0.01). Conversely, LMBR1 was decreased in PDLSCs cultured in OM (p < 0.001), with further reduction induced by PAR1 agonist and a reverse increase observed with PAR1 antagonist (p < 0.001). OE-LMBR1 transfection successfully elevated LMBR1 levels, subsequently inhibiting BMP2 and BMP4 (p < 0.001). Meanwhile, the Noggin protein effectively suppressed BMP2 and BMP4 (p < 0.001). All observed osteogenesis-related changes were reversed by the increased LMBR1 or inhibition of the BMP pathway (p < 0.001). Furthermore, NaB suppressed osteogenesis-related changes in OM-cultured PDLSCs (p < 0.001), and these effects were entirely reversed by PAR1 agonist (p < 0.001). Conversely, the increased LMBR1 or inhibited BMP pathway disrupted the osteogenesis reversion induced by PAR1 agonist (p < 0.001).

Conclusion: The activation of PAR1, through suppressing LMBR1 signaling and activating BMP pathway, demonstrates the ability to enhance the osteogenesis of PDLSCs and mitigate the inhibitory effects on PDLSCs osteogenesis caused by NaB.

Background: Severe neonatal hyperbilirubinemia can cause hearing impairment. Bilirubin can be deposited in nerve cells, and the brainstem and the 8th nerve are especially sensitive to bilirubin toxicity. Abnormal changes in brainstem auditory evoked potential (BAEP) can be observed, and the BAEP test measures a nerve potential induced by short, high-frequency sound stimulation; thus, it is able to detect damage to the auditory conduction pathway in children. We aimed to identify relationships between clinical features and BAEP abnormalities in children with hyperbilirubinemia and to assess the predictive power of these risk factors for bilirubin-induced neurological damage.

Methods: Children with hyperbilirubinemia were evaluated with BAEP and retrospectively enrolled in the study between January 2012 and December 2018. Multivariate logistic regression was performed to identify independent predictors of BAEP abnormalities.

Results: Of the 561 children with hyperbilirubinemia enrolled, the BAEP anomaly group accounted for 198 (35.3%) cases. Except for body weight, there were no significant differences in the general data between the two groups with hyperbilirubinemia (p > 0.05). Univariate analysis showed that prematurity, abnormal umbilical cord, and gestational diabetes during pregnancy were significantly correlated with abnormal BAEP. Multivariate logistic regression analysis identified prematurity (p = 0.001), gestational diabetes (p = 0.03), Premature rupture of membranes (p = 0.013), total serum bilirubin (TSB), bilirubin/albumin (B/A) as independent risk factors for BAEP abnormalities. The prediction accuracy of TSB (Area Under Curve (AUC) = 0.557) and B/A (AUC = 0.566) was low, indicating that abnormal BAEP should be detected by multiple factors.

Conclusions: Multivariate detection is beneficial for predicting the occurrence of auditory nerve injury in patients with hyperbilirubinemia.

Background: Remodeling of vascular smooth muscle cells (VSMCs), as a pathological hallmark of cardiovascular diseases, is related to the molecular rewiring of Calcium signaling, which induces upregulation of stromal interaction molecule (STIM) proteins. This study analyzed the influence of STIM1 proteins on the remodeling of VSMCs in atherosclerosis (AS).

Methods: After oxidized low-density lipoprotein (ox-LDL) treatment and transfection, VSMC viability, migration, and invasion were separately measured using Cell Counting Kit-8, Scratch assay, and Transwell assay. An animal AS model was constructed, and histological analysis via hematoxylin-eosin staining was conducted on the aorta.

Results: Ox-LDL promoted expression of STIM1 and Orai calcium release-activated calcium modulator 1 (Orai1). STIM1 or Orai1 downregulation suppressed viability, migration, invasion, and phenotypic switching of ox-LDL-treated VSMCs, whereas STIM1 or Orai1 upregulation had opposite effects. Orai1 level was upregulated by STIM1 overexpression. Orai1 silencing reversed the effects of STIM1 overexpression in VSMCs. STIM1 deficiency alleviated AS and regulated expression of Orai1 and phenotypic switch-related factors in vivo.

Conclusion: STIM1 deficiency suppresses viability, migration, invasion, and phenotypic switching of ox-LDL-induced VSMCs and alleviates AS by inhibiting Orai1.

Background: Cutaneous squamous cell carcinoma (cSCC) is a fatal disease characterized by metabolic dysregulation. The role of ephrin type-B receptor 2 (ephrin-B2), a crucial molecule in cancer cell biology, in regulating glycolysis and cell proliferation of cSCC is not well understood. This study aimed to investigate the biological pathways by which ephrin-B2 impacts the glycolysis and cell proliferation of cSCC.

Methods: Ephrin-B2 expression levels in cSCC were determined using quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and Western blotting. Ephrin-B2 expression in cSCC cells was manipulated using overexpression and knockdown approaches. A series of in vitro assays, such as cell counting kit-8 (CCK-8), Transwell assay, immunofluorescence assay, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blotting, were employed to delineate the biological roles of ephrin-B2/pyruvate kinase muscle isoenzyme 2 (PKM2)/hypoxia-inducible factor 1 alpha (HIF-1α) in proliferation, migration, invasion, and glucose metabolism of cSCC.

Results: This study highlights an upregulation of ephrin-B2 expression in cSCC. Knockdown of ephrin-B2 significantly suppressed the proliferation, migration, invasion, and glucose metabolism of cSCC cells. Moreover, ephrin-B2 expression was upregulated under hypoxic conditions. At the molecular level, ephrin-B2 knockdown resulted in the downregulation of PKM2 and HIF-1α expression. Additionally, the overexpression of PKM2 or HIF-1α successfully rescued the diminished proliferation, migration, invasion and glucose metabolism induced by ephrin-B2 knockdown in cSCC cells.

Conclusion: These findings suggest that ephrin-B2 suppression may hinder cSCC cell proliferation and glycolytic metabolism, potentially via the PKM2/HIF-1α axis modulation.

Background: This study aims to facilitate parental identification of designated emergency facilities for expeditious pediatric care within the framework of Taiwan's newly implemented “regional joint defense” approach to pediatric emergency services. The research seeks to elucidate the mechanisms by which this novel system can enhance timely access to appropriate emergency care for children, potentially improving health outcomes and resource utilization in acute pediatric situations.

Methods: Factor analysis (FA) and triangular entropy matrix (TEM) analyzed the appearance, breathing and skin of pediatric assessment triangle (ABC of PAT), three types of prehospital pediatric emergence condition (PPEC), five levels of Taiwan's pediatric emergency triage (TPET), and applied the social learning theory (SLT) in educational doctrine, using experts' weighted questionnaires.

Results: Firstly, to address deficiencies in Taiwan's pediatric prehospital emergency medicine (PEM) system, integrating emergency medical knowledge (EMK) and pediatric life support (PLS) into medical education, staff training, and the national handbook for new parents is crucial. This equips parents to manage children's illnesses and prevent emergencies. Then, in life-threatening situations, immediate emergency room (ER) transport is vital for symptoms like whitish or purple lips, cold limbs, mottled skin, cold sweat, convulsions, dyspnea, chest dimples, weak consciousness, and oxygen saturation below 94%. Finally, for non-life-threatening emergencies, seek medical evaluation if symptoms include wheezing, chest tightness, chest pain, persistent high fever over 39 degrees with convulsions, chills, cold sweats, not eating or urinating for over 12 hours, or fever lasting more than 48 hours.

Conclusion: Parents must remain calm and provide their baby with a sense of security while observing the development of physical symptoms. This approach enables them to effectively determine the most appropriate time to take their children to the emergency room, thereby avoiding life-threatening emergencies. Prompt and proper measures and treatments not only alleviate various discomforts caused by illness or medical emergencies but also reduce systemic distress, life-threatening situations, and unfortunate incidents before hospitalization.

Background: Bile duct injury (BDI) is a severe complication following cholecystectomy and is therefore a particularly concerning surgical predicament for hepatobiliary surgeons. Owing to very high medical compensation awarded to patients suffering from BDI, surgeons need to exercise caution during surgery to avoid BDI. Herein, we explored a novel method to identify cystic duct during laparoscopic cholecystectomy (LC), expanding the applicability of this surgical approach.

Methods: Patients receiving LC between April 2021 and October 2022 at the Gaoyou People's Hospital were included in this retrospective clinical study and divided into two groups according to whether the cystic duct was incised (one group with LC alone, while another with laparoscopic cholecystectomy and cystic duct exploration [LCCDE]). Clinical and baseline characteristics of patients were collected, and the preoperative and postoperative biochemical parameters were compared. The surgical outcomes of LCCDE were observed.

Results: A total of 114 patients had undergone LC, while 162 patients had received LCCDE as treatment. There were no significant differences in age, gender, common bile duct diameter, preoperative and postoperative biochemical parameters between the two groups. No significant difference in the mean operation time between the LC and LCCDE groups was noted (p = 0.409). In the LCCDE group, white secretions in the cystic duct were observed in 92 patients (56.8%).

Conclusions: The presence of intraoperative white secretions in the cystic duct may further confirm the presence of cystic duct, thereby enabling earlier detection of BDI. Importantly, LCCDE, as the new surgical method explored in this study, does not extend the operation time.

Background: Hyperlipidemia is one of the main causes of aggravated hepatic ischemia-reperfusion injury (IRI). Simvastatin (SIM), a lipid-lowering drug, has been shown to effectively alleviate IRI caused by hyperlipidemia. However, the regulatory mechanism by which SIM alleviates hyperlipidemia-induced hepatic IRI is still not clear. This study aims to explore the potential mechanisms of SIM in inhibiting hyperlipidemia-induced hepatic IRI, providing new therapeutic strategies for the alleviation of hepatic IRI.

Methods: An animal model of hyperlipidemia was induced by feeding mice a high-fat diet for 8 weeks. Subsequently, a hepatic IRI animal model of hyperlipidemia was established by occluding the hepatic artery and portal vein for one hour, followed by reperfusion for 6 or 12 h. Enzyme linked immunosorbent assay, Western blotting, hematoxylin-eosin (H&E) staining, immunohistochemistry, immunofluorescence, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling assay, were used to evaluate liver injury, neutrophil extracellular traps (NETs) formation, and related molecular mechanisms.

Results: Hepatic IRI was accelerated by hyperlipidemia, which enhanced the expression of oxidized low-density lipoprotein (oxLDL) and Macrophage-1antigen (Mac-1), leading to the promotion of NETs formation and apoptosis of liver cells. The administration of simvastatin reduced the levels of oxLDL and Mac-1, decreased the formation of NETs, and alleviated hepatic IRI induced by hyperlipidemia.

Conclusions: Simvastatin reduced hyperlipidemia-induced hepatic IRI by inhibiting the formation of NETs through the regulation of the oxLDL/Mac-1 pathway.

Objective: Cervical cancer (CC) ranks among the most prevalent malignant tumors affecting the female reproductive system. Nonetheless, various shortcomings exist within current treatment approaches for CC. Therefore, the quest for new intervention targets holds significant importance. Research has demonstrated that long non-coding RNA (lncRNA) long intergenic non-protein coding RNA 2487 (LINC02487) can suppress the development of oral squamous cell carcinoma (OSCC). However, its function and potential mechanisms in CC remain unclear, therefore, this study aims to investigate the role and potential mechanism of LINC02487 in CC.

Methods: LINC02487 and phosphatase and tensin homolog (PTEN) expression were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) in CC tissue samples and constructed cell models. LINC02487 was either knocked down or overexpressed, and PTEN was knocked down in the CC (SiHa) cell line via transfection technology. The expression levels of LINC02487 and PTEN in SiHa cell lines were examined using RT-qPCR after various treatments. Cell proliferation ability was determined through Cell Counting Kit (CCK)-8 and colony formation assays, while the ability to invade and migrate was assessed via Transwell experiments. Western blot analysis was employed to measure the levels of key proteins in the PTEN/Akt/mechanistic target of the rapamycin (mTOR) signaling pathway.

Results: A positive correlation was observed between LINC02487 and PTEN, both of which were found to be downregulated in CC cells and tissues (p < 0.05). In vitro experiments demonstrated that overexpression of LINC02487 significantly inhibited colony formation (p < 0.01), invasion (p < 0.01), migration (p < 0.01), and proliferation (p < 0.01) of SiHa cells. Furthermore, LINC02487 overexpression led to upregulation of PTEN expression (p < 0.01) and inhibition of the Akt/mTOR signaling pathway (p < 0.01), while knockdown of LINC02487 produced the opposite effect (p < 0.01). Additionally, knocking down PTEN counteracted the inhibitory effects of LINC02487 overexpression on CC progression (p < 0.01) and the Akt/mTOR signaling pathway (p < 0.01).

Conclusion: In vitro findings suggest that LINC02487 may impede the progression of CC by suppressing the Akt/mTOR signaling pathway through the upregulation of PTEN expression. Consequently, LINC02487 holds promise as a potential therapeutic target for the treatment of CC.

Background: Cerebral ischemia-reperfusion injury (CIRI) is a prevalent neurological disorder, characterized by the oxidative stress and inflammatory response induced during the ischemia-reperfusion process, leading to significant damage to brain cells. Ginsenoside Rb1, a natural medicinal ingredient, possesses potential neuroprotective effects. This study aims to investigate the mechanism of action of ginsenoside Rb1 in CIRI and its protective effects on brain injury.

Methods: We utilized a mouse CIRI model and randomly divided the mice into control group, CIRI group, and ginsenoside Rb1 treatment group. The effects of Rb1 on brain tissue damage, apoptosis, expression of inflammatory factors, and pyroptotic cell numbers in CIRI mice were observed through triphenyl tetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, real-time reverse transcription polymerase chain reaction (qRT-PCR), and electron microscopy. In a cell model, the regulatory effect of Rb1 on oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell pyroptosis via the nuclear respiratoty factor 2/tumor necrosis factor-α (TNF-α)-induced Protein 3 (TNFAIP3, aka A20)/eukaryotic translation elongation factor 1A2 (Nrf2/A20/eEF1A2) axis was detected using Western blot and TUNEL staining. Additionally, the impact of Nrf2 inhibitor ML385 and eEF1A2 overexpression on the neuroprotective effect of Rb1 was assessed. Using the comprehensive experimental methods mentioned above, the neuroprotective mechanism of Rb1 in CIRI was thoroughly evaluated.

Results: Our findings demonstrate that treatment with ginsenoside Rb1 alleviated behavioral deficits induced by CIRI and reduced pathological damage in brain tissue. Furthermore, ginsenoside Rb1 treatment notably decreased oxidative stress and the inflammatory response induced by CIRI, leading to lower levels of inflammatory factors (p < 0.05). Further experimental results indicated that ginsenoside Rb1 promoted antioxidant and anti-inflammatory responses by regulating the activity of the Nrf2/A20/eEF1A2 axis. Additionally, ginsenoside Rb1 inhibited the activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, thereby reducing the release of inflammatory factors and the occurrence of cell apoptosis.

Conclusion: Our study results suggest that ginsenoside Rb1 exerts neuroprotective effects and alleviates brain injury induced by CIRI by regulating the Nrf2/A20/eEF1A2 axis and inhibiting the activation of the NLRP3 inflammasome. These findings provide new treatment insights for CIRI and support ginsenoside Rb1's development as a therapeutic drug. However, despite the promising nature of our findings, further research is required to validate these discoveries and explore the feasibility and safety of ginsenoside Rb1 in clinical applications. We hope that our study can provide new directions and strategies for the treatment and prevention of CIRI, contributing to the development of neuroprotective drugs.