6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

OBJECTIVES: To investigate the clinical and immunological features of children with primary immune thrombocytopenia (pITP) or connective tissue disease (CTD) with thrombocytopenia as the initial manifestation at initial diagnosis, and to provide a basis for early differentiation. METHODS: A retrospective study was performed on 236 children with pITP (pITP group) or CTD with thrombocytopenia as the initial manifestation (CTD-TP group) who were admitted from January 2019 to August 2024. Clinical and immunological indicators were compared between the two groups to identify potential influencing factors for early differentiation and their discriminative validity. RESULTS: Compared with the pITP group, the CTD-TP group had a significantly older age of onset and significantly lower leukocyte count, eosinophil count, lymphocyte count, and complement C4 level (P<0.05), as well as significantly higher levels of C-reactive protein, IgE, and IgM (P<0.05). The logistic regression analysis showed that age, IgE, IgM, total B cells, and complement C4 were predictive factors for early differentiation between pITP and CTD-TP (P<0.05). The receiver operating characteristic curve analysis showed that a combination of these five factors had a good discriminative validity, with an area under the curve of 0.944. The correlation analysis showed a negative correlation between IgG and platelet count in the pITP group (r_s=-0.363, P<0.05) and a positive correlation between NK cells and platelet count in the CTD-TP group (r_s=0.713, P<0.05). CONCLUSIONS There is heterogeneity in the clinical and immunological indicators between children with pITP and CTD-TP at initial diagnosis, and these research findings can help with the early differentiation between the two diseases.
Purpura, Thrombocytopenic, Idiopathic/immunology* ; Diagnosis, Differential ; Connective Tissue Diseases/immunology* ; Retrospective Studies ; Early Diagnosis ; Age of Onset ; Leukocyte Count ; Complement C4/immunology* ; C-Reactive Protein/immunology* ; Immunoglobulin E/immunology* ; Immunoglobulin M/immunology* ; Humans ; Male ; Female ; Infant ; Child, Preschool ; Child ; Adolescent ; Biomarkers/blood*

OBJECTIVE: To explore the functional roles and underlying mechanisms of neferine in the context of angiotensin II (Ang II)-induced hypertension and vascular dysfunction. METHODS: Male mice were infused with Ang II to induce hypertension and randomly divided into treatment groups receiving neferine or a control vehicle based on baseline blood pressure using a random number table method. The hypertensive mouse model was constructed by infusing Ang II via a micro-osmotic pump (500 ng/kg per minute), and neferine (0.1, 1, or 10 mg/kg), valsartan (10 mg/kg), or double distilled water was administered intragastrically once daily for 6 weeks. A non-invasive blood pressure system, ultrasound, and hematoxylin and eosin staining were performed to assess blood pressure and vascular changes. RNA sequencing and network pharmacology were employed to identify differentially expressed transcripts (DETs) and pathways. Vascular ring tension assay was used to test vascular function. A7R5 cells were incubated with neferine for 24 h and then treated with Ang II to record the real-time Ca²⁺ concentration by confocal microscope. Immunohistochemistry (IHC) and Western blot were used to evaluate vasorelaxation, calcium, and the extracellular signal-regulated kinase (ERK)1/2 pathway. RESULTS: Neferine treatment effectively mitigated the elevation in blood pressure, pulse wave velocity, aortic thickening in the abdominal aorta of Ang II-infused mice (P<0.05). RNA sequencing and network pharmacology analysis identified 355 DETs that were significantly reversed by neferine treatment, along with 25 potential target genes, which were further enriched in multiple pathways and biological processes, such as ERK1 and ERK2 cascade regulation, calcium pathway, and vascular smooth muscle contraction. Further investigation revealed that neferine treatment enhanced vasorelaxation and reduced Ca²⁺-dependent contraction of abdominal aortic rings, independent of endothelium function (P<0.05). The underlying mechanisms were mediated, at least in part, via suppression of receptor-operated channels, store-operated channels, or voltage-operated calcium channels. Neferine pre-treatment demonstrated a reduction in intracellular Ca²⁺ release in Ang II stimulated A7R5 cells. IHC staining and Western blot confirmed that neferine treatment effectively attenuated the upregulation of p-ERK1/2 both in vivo and in vitro, which was similar with treatment of ERK1/2 inhibitor PD98059 (P<0.05). CONCLUSIONS Neferine remarkably alleviates Ang II-induced elevation of blood pressure, vascular dysfunction, and pathological changes in the abdominal aorta. This beneficial effect is mediated by the modulation of multiple pathways, including calcium and ERK1/2 pathways.
Animals ; Angiotensin II ; Male ; Benzylisoquinolines/therapeutic use* ; Network Pharmacology ; Blood Pressure/drug effects* ; Sequence Analysis, RNA ; Mice ; Hypertension/chemically induced* ; Mice, Inbred C57BL ; Calcium/metabolism*

Objective To explore the changes in cerebral blood flow caused by mandibular retrusion,as well as the impact and potential mechanisms on stroke recovery.Methods 6-week-old SD male rats were selected as experi-mental subjects.The metal cannula was bonded to the rat maxillary incisor for one week,forcing mandibular retru-sion(MR).Cerebral blood flow was detected by laser speckle imaging.Cognitive function was detected by the Morris water.Then,the stroke model was constructed in MR rats by using the middle cerebral artery occlusion(MCAO)method for one week.Meanwhile,metal cannulae were then removed in rats to restore the lower jaw's position(MCAO RO),serving as a positive control group.Consequently,rats were randomly divided into the fol-lowing groups:Sham groups,MCAO groups,MCAO MR groups,and MCAO RO groups.Neurological recovery was assessed through the modified neurological severity score(mNSS).The area of cerebral infarction was evalua-ted by using triphenyltetrazolium(TTC)staining.The changes in nerve cells were observed by using hematoxylin eosin(HE)staining.The protein expression level of vascular endothelial growth factor(VEGF)was detected by immunohistochemistry.The protein expression levels of platelet-endothelial cell adhesion molecule(CD31),sirtuin 6(SIRT6),and thioredoxin interaction protein(TXNIP)were detected by Western blot.The mRNA expression levels of SIRT6,TXNIP,and VEGF were determined by qRT-PCR.Microglia activation marker molecule 1(IBA-1)was detected by immunofluorescence.Resluts Because of mandibular retrusion,laser speckle showed de-creased cerebral blood flow,and the water maze showed decreased cognitive function.Compared to other groups,MCAO MR showed a larger ischemic area in TTC staining,while HE staining and neurological scoring showed poo-rer neurological function recovery.Western blot and qRT-PCR showed that the MCAO MR group inhibited the mR-NA and protein expression levels of SIRT6,upregulated the mRNA and protein expression levels of TXNIP,and in-creased the activation of microglia.Conclusion Mandibular retrusion reduces cerebral blood flow and alters cogni-tive function in rats.Mandibular retrusion inhibits recovery in stroke through the SIRT6/TXNIP axis.

Objective: To obtain the diversity and abundance of fast-growing bacteria in the surface water of the northeast coast of Hainan Island in China, different cultivation methods were employed. This study also aims to provide a reference for isolating bacterial samples from seawater sources and preventing marine-derived pathogens. Methods: Based on the principles of taxonomic design, surface seawater samples were collected from six locations along the northeast coast of Hainan Island in China in March, June, October, and December 2021. Then, bacterial enrichment was performed based on traditional cultivation methods for Salmonella, Vibrio, Burkholderia pseudomallei, Actinomycetes, and general marine bacteria. After that, bacterial species identification was conducted by 16S rDNA amplicon sequencing and metagenomic sequencing. Results: A total of 1 151 fast-growing cultivable bacteria belonging to 66 genera and 213 species were identified using five different culture protocols. In different cultivation protocols, Bacillus and Klebsiella demonstrated extensive discriminatory advantages and ranked among the top genera in terms of abundance. Protocol 1 had Escherichia, Klebsiella, and Citrobacter as dominant genera. Pathogenic bacteria detected by protocol 1 included Klebsiella pneumoniae and Escherichia coli, with 37 and 29 strains respectively, while Salmonella enterica was uniquely detected with seven isolates. Proteus, Enterococcus, and Providencia were the dominant genera in protocol 2, and Proteus mirabilis was the most abundant pathogenic bacteria detected with 66 isolates. Vibrio cholerae was uniquely detected with six isolates at a higher abundance. Klebsiella, Escherichia, and Acinetobacter were the dominant genera in protocol 3, and Klebsiella pneumoniae was the most abundant pathogenic bacteria detected with 53 isolates, while Acinetobacter nosocomialis was uniquely detected with seven isolates. Vibrio and Pseudoalteromonas were the dominant genera in protocol 4, and they showed advantages in isolating and cultivating Marine-derived Vibrio. Exiguobacterium, Staphylococcus, and Bacillus were the dominant genera in protocol 5. Bacillus cereus and Lactococcus lactis were the most abundant pathogenic bacteria detected with 20 and 15 isolates, respectively, while Lactococcus lactis was uniquely detected at higher abundance. Metagenomic sequencing showed that Klebsiella pneumoniae was significantly dominant with a gene abundance of 51.11%, followed by Alcanivorax sp. at 12.57%. Conclusion: The surface water of the northeast coast of Hainan Island in China exhibits a rich diversity of bacteria, with Klebsiella pneumoniae being highly abundant in the studied area. Different cultivation methods demonstrate distinct selective advantages in culturing bacterial genera and pathogens. Therefore, it is necessary to optimize cultivation conditions for specific marine bacteria.
Humans ; Water ; Bacteria/genetics* ; Seawater/microbiology* ; Escherichia coli ; Enterococcus ; Klebsiella pneumoniae ; China

Objective To evaluate the efficacy,safety and cost-effectiveness of alirocumab for the treatment of hypercholesterolemia in a rapid health technology assessment(rHTA).Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data and health technology assessment(HTA)relative websites were electronically searched to collect HTA reports,systematic reviews/Meta-analyses and pharmacoeconomic literatures on the alirocumab for the treatment of hypercholesterolemia from inception to August 14th,2022.Two reviewers independently screened the literature,extracted the data results and accessed the quality of included studies.Descriptive analysis and summary were then performed.Results A total of 38 documents were included,including 28 systematic reviews/Meta analyses,7 pharmacoeconomic studies and 3 HTA reports.This study showed that,compared with placebo or other lipid lowering therapy,alirocumab lowered the levels of LDL-C,Lp(a),TC,TG,Apo B,non-HDL-C,increased the levels of HDL-C and Apo A1,reduced the risk of major adverse cardiovascular events(MACE),all-cause mortality,cerebrovascular events,and unstable angina,but did not reduce cardiovascular death,myocardial infarction or coronary revascularization.Safety studies showed that,compared with placebo or other lipid lowering therapy,alirocumab did not increase the risk of other adverse reactions but associated with higher injection site reactions.Pharmacoeconomic studies showed that alirocumab was cost-effective in patients with three branch coronary artery disease and acute coronary syndrome with LDL-C≥2.59 mmol·L-1.Conclusion Alirocumab is effective and safe for the treatment of hypercholesterolemia,and cost-effective for the patients of coronary arteriosclerotic heart disease with multi-vessel disease or with high base-line level of LDL-C.

Abstract: Objective　To analyze the epidemiological characteristics (season, age, gender, mixed infection and clinical manifestations, etc.) of Mycoplasma pneumoniae (MP) infection in children in Hainan Province, so as to provide epidemiological evidence-based medical basis for the prevention and control of MP infection in children in Hainan Province. Methods　The serum IgM antibodies of MP, Legionella pneumophila, Chlamydia pneumoniae, adenovirus, respiratory syncytial virus (RSV), Q fever Rickettsia, parainfluenza virus, influenza A virus and influenza B virus in children with respiratory tract infections (RTIs) who were hospitalized in pediatrics of many hospitals in Hainan Province from March 2012 to February 2020 were detected by indirect immunofluorescence method. The positive serum MP-IgM antibody was defined as MP infection. The epidemiological and clinical data of MP infected cases were analyzed retrospectively. Results　From March, 2012 to February, 2020, a total of 35 731 qualified pediatric inpatients with RTIs in many hospitals in Hainan Province were tested for serum MP-IgM with the total positive rate of 39.12% (13 978/35 731). The yearly positive rates of MP-IgM from 2012 to 2020 were 48.39%, 56.23%, 56.62%, 47.04%, 29.71%, 24.14%, 47.55%, 36.84% and 24.46% respectively. The positive rates of MP-IgM in 2013 and 2014 were significantly higher than those in other years (P<0.05). The positive rate of MP-IgM in summer in Hainan Province was the highest (41.34%) and the lowest in winter (35.77%) (P<0.05). MP infection occurred in all age groups, the positive rate of MP-IgM in children of preschool (51.80%) was significantly higher than that in other age groups (P<0.01), and the positive rate of MP IgM in children of infancy (15.36%) was lower than that in other age groups (P<0.01). The positive rate of MP-IgM in female was 44.77%, which was significantly higher than that in male (35.83%) (P<0.05). MP infection combined with positive IgM of another pathogen accounted for 32.63% (4 561 cases), positive IgM of another two pathogens accounted for 1.26% (176 cases). MP infection was mostly found in pneumonia (68.73%), and the main clinical symptoms were cough (84.72%), fever (51.01%) and wheezing (3.16%). Conclusions　MP is an important pathogen of respiratory tract infection in children in Hainan Province, and infection is more common in children in early school age and early childhood. Mp-specific tests should be performed to identify the pathogen in children suspected of MP infection. In the high incidence season, health education should be strengthened in kindergartens, schools and other places to prevent respiratory tract infection.