Vertebral Artery Stenting for Acute Multiple Cerebral Infarctions Caused by Vertebral Artery Dissection After Massage: A Case Report.

Vertebral artery dissection is a rare pathology that causes ischemic stroke in young people. Cervical massage, especially improper pulling manipulation, is a cause of vertebral artery dissection. We present a case of 32-year-old woman who developed acute multiple posterior circulation ischemic cerebral infarctions as a result of left vertebral artery V4 segment dissection after receiving neck massage. She underwent emergency vertebral artery stent implantation at the site of the dissection. Symptoms were relieved the day after treatment. The patient recovered without adverse complications or endovascular restenosis in the following year.

A c.726C>G (p.Tyr242Ter) nonsense mutation-associated with splicing alteration (NASA) of WDR45 gene underlies ß-propeller protein-associated neurodegeneration (BPAN).

Neurodegeneration with brain iron accumulation (NBIA) is a clinically and genetically heterogeneous disease characterized by increased iron deposition in the basal ganglia and progressive degeneration of the nervous system in adulthood. However, in early childhood, there were no characteristic features to perform early diagnosis. In our study, a female child exhibited global developmental delay, intellectual disability, and febrile seizure without other distinct clinical phenotypes. Through whole exome sequencing (WES), a de novo nonsense mutation (c.726C > G, p. Tyr242Ter) of WDR45 gene was identified in this child. She was finally diagnosed as ß-propeller protein-associated neurodegeneration (BPAN), one of the recently identified subtypes of NBIA. This mutation could act as a premature stop codon (PSC) which rendered the mutated transcripts to be degraded by nonsense-mediated mRNA decay (NMD), leading to decreased levels of PSC-containing mRNAs. Additionally, through mini-gene splicing assays, this mutation could result in an unprecedented novel transcript with the exon 9 of WDR45 excluded by nonsense-associated splicing alteration (NASA). Transcriptome sequencing (RNA-seq) on total RNAs from PBMCs of the trio revealed three types of alternative splicing events in the patient. Further research implied that downregulation of iron transport genes (TFRC, TFR2, SCARA5) might be the underlying mechanism for the iron accumulation in patients with deficient WDR45. This is the first report about NASA happening in WDR45. It implies that nonsense mutations approximal to splicing sites could affect the disease pathogenesis through more than one molecular mechanism and should be taken into consideration when conducting genetic counseling.

Emodin improves the cardiac function in the rats with chronic heart failure through regulation of the miR-26b-5p/PTEN pathway.

Introduction: Chronic heart failure (CHF) is a leading cause of deaths induced by cardiovascular disease. This study aimed to investigate the protective effects of emodin in CHF rats and explore the related mechanisms. Material and methods: A total of 56 Wistar rats were used to construct CHF model using the coronary artery ligation. The effects of emodin on cardiac function and inflammation were analyzed in the CHF rats. Expression of miR-26b-5p in the CHF model before and after emodin treatment was estimated by quantitative real-time polymerase chain reaction. The effects of miR-26b-5p on cardiac function and inflammation were also assessed, and its target gene was predicted and confirmed in rat cardiomyocyte H9c2. Results: Emodin treatment could significant improve the cardiac function and inflammation evidenced by the increased increased ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP) and maximum of the first differentiation of left ventricular pressure (+LV dP/dtmax) and decreased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), left ventricular end diastolic pressure (LVEDP), interleukin (IL)-6, tumor necrosis factor α (TNF-α) levels. Expression of miR-26b-5p was downregulated in the CHF rats (CHF 0.442 ±0.131 vs. Sham 1.044 ±0.160), and this suppressive effect was rescued by emodin (Emodin 0.902 ±0.132 vs. CHF 0.442 ±0.131). The overexpression of miR-26b-5p in CHF rats led to improved cardiac function and inflammatory response. In addition, the emodin-induced increased EF, FS, LVSP and +LV dP/dtmax and decreased ANP, BNP, LVEDP, IL-6 and TNF-α were all abrogated by the knockdown of miR-26b-5p. The target prediction results revealed that PTEN was a target gene of miR-26b-5p in H9c2 cells. Conclusions: All the results indicated that emodin serves a protective role in CHF via regulation of the miR-26b-5p/PTEN pathway. Emodin may be an effective therapeutic agent for CHF treatment.

Associations of quantitative contrast sensitivity with vascular metrics on widefield swept-source OCT angiography across stages of diabetic retinopathy.

PURPOSE: To investigate structure-function associations between contrast sensitivity (CS) and widefield swept-source optical coherence tomography angiography (WF SS-OCTA) vascular metrics across stages of non-proliferative (NPDR) and proliferative diabetic retinopathy (PDR), without diabetic macular oedema. METHODS: Prospective cross-sectional study in 140 eyes of 99 patients: 33 mild NPDR, 24 moderate/severe NPDR, 15 PDR, 33 diabetic without DR (DMnoDR) and 46 control eyes. Mixed-effects multivariable regression models to evaluate associations between quantitative contrast sensitivity function (Adaptive Sensory Technology) and vessel density (VD) and vessel skeletonised density (VSD) in the superficial capillary plexus (SCP) and deep capillary plexus (DCP) on same-day imaging with WF SS-OCTA (Plex Elite 9000, Carl Zeiss Meditec). RESULTS: Standardised ß coefficients for area under the logarithm of contrast sensitivity function curve (AULCSF) versus visual acuity (VA) at 3×3 mm scans: SCP VSD (ß=0.32, p<0.001 vs -0.18, p=0.044), DCP VSD (ß=0.30, p<0.001 vs -0.21, p=0.02), SCP VD (ß=0.25, p=0.004 vs -0.13, p=0.129), DCP VD (ß=0.26, p=0.003 vs -0.19, p=0.034). AULCSF was significantly reduced in mild NPDR (ß=-0.28, p<0.001) and DMnoDR (ß=-0.19, p=0.005) versus controls, while VA was not significantly different. AULCSF performed better than VA in differentiating between controls and DMnoDR (0.69 vs 0.50), controls and mild NPDR (0.76 vs 0.61) and controls and moderate/severe NPDR (0.89 vs 0.73). CONCLUSIONS: DR-induced microvascular changes on OCTA are associated with larger changes on CS than in VA. CS is affected earlier than VA in the course of DR and performed better in discriminating between controls, DMnoDR and across DR stages.

A study on the association between prefrontal functional connectivity and non-suicidal self-injury in adolescents with depression.

Objective: Among adolescents with depression, the occurrence of non-suicidal self-injury (NSSI) behavior is prevalent, constituting a high-risk factor for suicide. However, there has been limited research on the neuroimaging mechanisms underlying adolescent depression and NSSI behavior, and the potential association between the two remains unclear. Therefore, this study aims to investigate the alterations in functional connectivity (FC) of the regions in the prefrontal cortex with the whole brain, and elucidates the relationship between these alterations and NSSI behavior in adolescents with depression. Methods: A total of 68 participants were included in this study, including 35 adolescents with depression and 33 healthy controls. All participants underwent assessments using the 17-item Hamilton Depression Rating Scale (17-HAMD) and the Ottawa Self-Harm Inventory. In addition, functional magnetic resonance imaging (fMRI) data of the participants' brains were collected. Subsequently, the FCs of the regions in the prefrontal cortex with the whole brain was calculated. The FCs showing significant differences were then subjected to correlation analyses with 17-HAMD scores and NSSI behavior scores. Result: Compared to the healthy control group, the adolescent depression group exhibited decreased FCs in several regions, including the right frontal eye field, left dorsolateral prefrontal cortex, right orbitofrontal cortex, left insula and right anterior cingulate coetex. The 17-HAMD score was positively correlated with the frequency of NSSI behavior within 1 year (rs = 0.461, p = 0.005). The FC between the right anterior cingulate cortex and the right precuneus showed a negative correlation with the 17-HAMD scores (rs = -0.401, p = 0.023). Additionally, the FC between the right orbitofrontal cortex and the right insula, demonstrated a negative correlation with the frequency of NSSI behavior within 1 year (rs = -0.438, p = 0.012, respectively). Conclusion: Adolescents with depression showed decreased FCs of the prefrontal cortex with multiple brain regions, and some of these FCs were associated with the NSSI frequency within 1 year. This study provided neuroimaging evidence for the neurophysiological mechanisms underlying adolescent depression and its comorbidity with NSSI behavior.

Fluoroquinolones and the risk of severe hypoglycaemia among sulphonylurea users: Population-based cohort study.

AIM: Fluoroquinolone-related hypoglycaemia is rare but may become clinically relevant in individuals at high baseline hypoglycaemic risk, such as patients with diabetes using sulphonylureas. Our population-based cohort study assessed whether fluoroquinolones are associated with an increased risk of severe hypoglycaemia compared with amoxicillin among patients treated with sulphonylureas. MATERIALS AND METHODS: Using the UK's Clinical Practice Research Datalink Aurum linked to hospitalization and vital statistics data, we assembled a base cohort of patients who initiated second-generation sulphonylureas (1998-2020). The study cohort included patients initiating either fluoroquinolones or amoxicillin while on sulphonylureas. Using an intent-to-treat exposure definition, we assessed the 30-day risk of severe hypoglycaemia (hospitalization with or death because of hypoglycaemia) associated with fluoroquinolones compared with amoxicillin. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs) of severe hypoglycaemia after 1:5 matching on previous sulphonylurea use and propensity scores. Secondary analyses were stratified by demographics and glycated haemoglobin. RESULTS: Overall, 143 417 patients initiated fluoroquinolones (n = 13 123) or amoxicillin (n = 130 294) while on sulphonylureas. Compared with amoxicillin, fluoroquinolones were not associated with the risk of severe hypoglycaemia (HR, 1.17; 95% CI, 0.91-1.50). Fluoroquinolones were associated with an increased risk in patients <65 years (HR, 2.90; 95% CI, 1.41-5.97) but not in those ≥65 years (HR, 1.03; 95% CI, 0.79-1.35) in stratified analyses. There was no evidence of effect modification by sex or glycated haemoglobin. CONCLUSIONS: In patients using second-generation sulphonylureas, fluoroquinolones were not associated with an increased risk of severe hypoglycaemia compared with amoxicillin. An increased risk among younger adults is possible.

Intravoxel incoherent motion diffusion-weighted imaging and dynamic contrast-enhanced MRI for predicting parametrial invasion in cervical cancer.

PURPOSE: This study aimed to assess the predictive efficacy of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in parametrial invasion (PMI) in cervical cancer patients. METHODS: A total of 83 cervical cancer patients (32 PMI-positive and 51 PMI-negative) retrospectively underwent pretreatment IVIM-DWI and DCE-MRI scans. IVIM-DWI parameters included apparent diffusion coefficient (ADC), slow apparent diffusion coefficient (D), fast apparent diffusion coefficient (D*), and perfusion fraction (f). DCE-MRI parameters included volume transfer constant (Ktrans), flux rate constant (Kep), and fractional extravascular extracellular space volume (Ve). Logistic regression analyses were conducted to identify independent variables associated with PMI. Receiver operating characteristic curves were generated to assess the predictive performance of significant parameters. RESULTS: Multivariable analysis revealed that the MRI parameters D (odds ratio [OR]: 7.05; 95% CI 1.78-27.88; P = 0.005), D* (OR 6.58; 95% CI 1.49-29.10; P = 0.01), f (OR 5.12; 95% CI 1.23-21.37; P = 0.03), Ktrans (OR 4.60; 95% CI 1.19-17.81; P = 0.03), and Kep (OR 4.90; 95% CI 1.25-19.18; P = 0.02) were independent predictors of PMI in cervical cancer patients. The combined parameter incorporating these parameters demonstrated the highest performance in predicting PMI, yielding an area under the curve of 0.906, sensitivity of 84.4%, and specificity of 86.3%. CONCLUSION: The proposed combined parameter exhibited favorable performance in identifying PMI in cervical cancer patients.

The Association between Cyberbullying Victimization and Depression among Children: A Moderated Mediation Model.

Cyberbullying victimization is becoming more prevalent and adversely affects mental health. This research explores the relationship between the two variables and the underlying mechanism, especially for children, as the impact of mental health in childhood might last a lifetime. Primary school students (N = 344; Mage = 9.90; 43.90% girls) completed self-report questionnaires regarding cyberbullying victimization, self-perceived social competence, optimism, and depression at school. Gender and grade were controlled as covariates. Depression was positively predicted by cyberbullying victimization, while self-perceived social competence played a partially mediating role. In addition, optimism directly and indirectly moderated the effects of cyberbullying victimization on depression. Specifically, the effects were stronger for children with low levels of optimism. Therefore, efforts to enhance children's self-perceived social competence and optimism may reduce their depression resulting from cyberbullying victimization.

A case report of Transnasal Endoscopic Drainage for Upper Parapharyngeal Abscess.

We report a case of upper parapharyngeal abscess arising from progression of a central skull base osteomyelitis, in a patient with poorly controlled diabetes mellitus. Our case is unusual for its presentation in an upper parapharyngeal location, involvement of the skull base, and poor response to medical treatment, hence requiring transnasal endoscopic surgical drainage to achieve definitive treatment. Here, we share our experience with a safe and effective technique of transnasal endoscopic drainage of a parapharyngeal abscess. Laryngoscope, 2024.

"Turn-on" and pinhole-free ultrathin core-shell Au@SiO2 nanoparticle-based metal-enhanced fluorescent (MEF) chemodosimeter for Hg2.

This study reports a metal-enhanced fluorescence chemodosimeter for highly sensitive detection of Hg2+ ions. Silica-coated Au nanoparticles (Au@SiO2 NPs) with a pinhole-free 4-5 nm shell were synthesized and functionalized with a monolayer of turn-on fluorescent probes. Compared to other organic fluorescent probes suffering from poor biocompatibility and detection limits, this design of a monolayer of turn-on fluorescent probes immobilized on the Au@SiO2 NPs with a pinhole-free 4-5 nm shell avoids fluorescence quenching and allows the fluorescent probe within the field of the inner Au NPs to experience metal-enhanced fluorescence. With this design, the chemodosimeter permits fluorescence emission in the presence of Hg2+ ions, because they trigger the ring-opening reaction of the fluorescent probe immobilized on the Au@SiO2 NPs. Additionally, the fluorescent probe is distanced by the thin SiO2 shell from directly attaching to the metallic Au NPs, which not only avoids fluorescence quenching but allows the fluorescent probe within the long-ranged field of the inner Au NPs to experience metal-enhanced fluorescence. As a result, the detection limit for the chemodosimeter can reach up to 5.0 × 10-11 M, nearly two orders of magnitude higher than that achieved for the free fluorescent probe. We also demonstrate the acquisition of images of Hg2+ in HTC116 cells and zebrafish using a simple fluorescence confocal imaging technique. The fluorescence response results for HTC116 cells and zebrafish show that the probes can permeate into cells and organisms. Considering the availability of the many organic fluorescent probes that have been designed, the current designed metal-enhanced fluorescence chemodosimeter holds great potential for fluorescence detection of diverse species and fluorescence imaging.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

N-glycan biosignatures as a potential diagnostic biomarker for early-stage pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of less than 10%, owing to its late-stage diagnosis. Early detection of pancreatic cancer (PC) can significantly increase survival rates. AIM: To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis. METHODS: An extensive patient cohort was used to determine a biomarker signature, including patients with PDAC that was well-defined at an early stage (stages I and II). The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I, 22 with stage II, 4 with stage III, 16 with stage IV PDAC, and 88 controls. We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan signature-based diagnosis model called the "Glyco-model". RESULTS: The biomarker signature was created to discriminate samples derived from patients with PC from those of controls, with a receiver operating characteristic area under the curve of 0.86. In addition, the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls, with a receiver operating characteristic area under the curve of 0.919. Glyco-model demonstrated favorable diagnostic performance in all stages of PC. The diagnostic sensitivity for stage I PDAC was 89.66%. CONCLUSION: In a prospective validation study, this serum biomarker signature may offer a viable method for detecting early-stage PDAC.

Effects of silencing hsa_circ_0015326 on proliferation, migration, invasion, and apoptosis of epithelial ovarian cancer cells.

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of death due to its complexity, heterogeneity, rapid metastasis and easy recurrence after surgical resection. We demonstrated that combination therapy with transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), Epclusa, Lenvatinib and Sintilimab is useful for patients with advanced HCC. CASE SUMMARY: A 69-year-old man who was infected with hepatitis C virus (HCV) 30 years previously was admitted to the hospital with abdominal pain. Enhanced computed tomography (CT) revealed a low-density mass in the right lobe of the liver, with a volume of 12.9 cm × 9.4 cm × 15 cm, and the mass exhibited a "fast-in/fast-out" pattern, with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL. Therefore, he was judged to have advanced HCC. During treatment, the patient received three months of Epclusa, three TACE treatments, two HAIC treatments, three courses of sintilimab, and twenty-one months of lenvatinib. In the third month of treatment, the patient developed severe side effects and had to stop immunotherapy, and the Lenvatinib dose had to be halved. Postoperative pathological diagnosis indicated a complete response. The patient recovered well after the operation, and no tumor recurrence was found. CONCLUSION: Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect. Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Promotion of self-directed learning abilities among Chinese medical students through preparing for career calling and enhancing teaching competencies in medical education: a cross-sectional study.

BACKGROUND: Medical students face a heavy burden as they are tasked with acquiring a vast amount of medical knowledge within a limited time frame. Self-directed learning (SDL) has become crucial for efficient and ongoing learning among medical students. However, effective ways to foster SDL ability among Chinese medical students are lacking, and limited studies have identified factors that impact the SDL ability of medical students. This makes it challenging for educators to develop targeted strategies to improve students' SDL ability. This study aims to assess SDL ability among Chinese medical students and examine the effects of career calling and teaching competencies on SDL ability, as well as the possible mechanisms linking them. METHODS: Data were collected from 3614 respondents (effective response rate = 60.11%) using cross-sectional online questionnaires and analyzed using IBM SPSS Statistics 22.0. The questionnaire comprised a Demographic Characteristics Questionnaire, Self-directed Learning Ability Scale (Cronbach's alpha = 0.962), Teaching Competencies Scale, and Career Calling Scale. RESULTS: The average SDL ability score of Chinese medical students was 3.68 ± 0.56, indicating a moderate level of SDL ability. The six factors of the Self-directed Learning Ability Scale-self-reflection, ability to use learning methods, ability to set study plans, ability to set studying objectives, ability to adjust psychological state, and willpower in studying-accounted for 12.90%, 12.89%, 12.39%, 11.94%, 11.34%, and 8.67% of the variance, respectively. Furthermore, career calling was positively associated with SDL learning ability (ß = 0.295, p < 0.001), and SDL learning ability was positively associated with teaching competencies (ß = 0.191, p < 0.01). Simple slope analysis showed that when the level of teaching competencies was higher, the influence of career calling on SDL ability was stronger. CONCLUSIONS: Chinese medical students' SDL ability has room for improvement. Medical students could strengthen their willpower in studying by setting milestones goals with rewards, which could inspire their motivation for the next goals. Teachers should guide students to learn experience to improve students' reflective ability. Educators play a crucial role in bridging the gap between career calling education and SDL ability enhancement, highlighting the significance of optimal teaching competencies. Colleges should focus on strengthening teachers' sense of career calling and teaching competencies.

The protective effect of Macrostemonoside T from Allium macrostemon Bunge against Isoproterenol-Induced myocardial injury via the PI3K/Akt/mTOR signaling pathway.

Myocardial injury (MI) signifies a pathological aspect of cardiovascular diseases (CVDs) such as coronary artery disease, diabetic cardiomyopathy, and myocarditis. Macrostemonoside T (MST) has been isolated from Allium macrostemon Bunge (AMB), a key traditional Chinese medicine (TCM) used for treating chest stuffiness and pains. Although MST has demonstrated considerable antioxidant activity in vitro, its protective effect against MI remains unexplored. To investigate MST's effects in both in vivo and in vitro models of isoproterenol (ISO)-induced MI and elucidate its underlying molecular mechanisms. This study established an ISO-induced MI model in rats and assessed H9c2 cytotoxicity to examine MST's impact on MI. Various assays, including histopathological staining, TUNEL staining, immunohistochemical staining, DCFH-DA staining, JC-1 staining, ELISA technique, and Western blot (WB), were utilized to explore the potential molecular mechanisms of MI protection. In vivo experiments demonstrated that ISO caused myocardial fiber disorders, elevated cardiac enzyme levels, and apoptosis. However, pretreatment with MST significantly mitigated these detrimental changes. In vitro experiments revealed that MST boosted antioxidant enzyme levels and suppressed malondialdehyde (MDA) production in H9c2 cells. Concurrently, MST inhibited ISO-induced reactive oxygen species (ROS) production and mitigated the decline in mitochondrial membrane potential, thereby reducing the apoptosis rate. Moreover, pretreatment with MST elevated the expression levels of p-PI3K, p-Akt, and p-mTOR, indicating activation of the PI3K/Akt/mTOR signaling pathway and consequent protection against MI. MST attenuated ISO-induced MI in rats by impeding apoptosis through activation of the PI3K/Akt/mTOR signaling pathway. This study presents potential avenues for the development of precursor drugs for CVDs.

Protective effects of ginsenoside F2 on isoproterenol-induced myocardial infarction by activating the Nrf2/HO-1 and PI3K/Akt signaling pathways.

BACKGROUND: Ginsenoside F2 (GF2) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown. PURPOSE: The purpose of this study is to investigate the protective effect and the underlying mechanisms of GF2 against isoproterenol (ISO)-induced MI. METHODS: ISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF2. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques. RESULTS: In vivo experiments, our results indicated that GF2 significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF2 notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF2 suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF2 effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF2 considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways. CONCLUSION: Taken together, GF2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.

imply: improving cell-type deconvolution accuracy using personalized reference profiles.

Using computational tools, bulk transcriptomics can be deconvoluted to estimate the abundance of constituent cell types. However, existing deconvolution methods are conditioned on the assumption that the whole study population is served by a single reference panel, ignoring person-to-person heterogeneity. Here, we present imply, a novel algorithm to deconvolute cell type proportions using personalized reference panels. Simulation studies demonstrate reduced bias compared with existing methods. Real data analyses on longitudinal consortia show disparities in cell type proportions are associated with several disease phenotypes in Type 1 diabetes and Parkinson's disease. imply is available through the R/Bioconductor package ISLET at https://bioconductor.org/packages/ISLET/ .

Vaccine adjuvants: current status, research and development, licensing, and future opportunities.

Vaccines represent one of the most significant inventions in human history and have revolutionized global health. Generally, a vaccine functions by triggering the innate immune response and stimulating antigen-presenting cells, leading to a defensive adaptive immune response against a specific pathogen's antigen. As a key element, adjuvants are chemical materials often employed as additives to increase a vaccine's efficacy and immunogenicity. For over 90 years, adjuvants have been essential components in many human vaccines, improving their efficacy by enhancing, modulating, and prolonging the immune response. Here, we provide a timely and comprehensive review of the historical development and the current status of adjuvants, covering their classification, mechanisms of action, and roles in different vaccines. Additionally, we perform systematic analysis of the current licensing processes and highlights notable examples from clinical trials involving vaccine adjuvants. Looking ahead, we anticipate future trends in the field, including the development of new adjuvant formulations, the creation of innovative adjuvants, and their integration into the broader scope of systems vaccinology and vaccine delivery. The article posits that a deeper understanding of biochemistry, materials science, and vaccine immunology is crucial for advancing vaccine technology. Such advancements are expected to lead to the future development of more effective vaccines, capable of combating emerging infectious diseases and enhancing public health.