Natural arabinogalactan， an important polysaccharide， has a wide range of sources， a complex structure， various biological activities， and great application potential. Natural arabinogalactan is mainly rich in plants and microorganisms， and its structure varies due to different sources， including types Ⅰ， type Ⅱ， type Ⅱ-related types， and new configurations. Natural arabinogalactan has shown a variety of biological activities， such as anti-tumor， anti-oxidation， anti-coagulation， anti-aging， blood glucose-lowering， intestinal health-maintaining， anti-inflammatory， and immunomodulatory activities. In addition， natural arabinogalactan shows good biocompatibility and low toxicity， serving as a potential material in the biomedical field. Natural arabinogalactan has been designed as a carrier in the drug delivery system to effectively improve drug stability and targeting. Natural arabinogalactan is often added to skin care products to help delay skin aging and enhance skin barrier function because of their moisturizing and antioxidant properties. Additionally， natural arabinogalactan acts as a thickener， stabilizer， and emulsifier to improve the texture and taste while enhancing the nutritional value of food products. The review of latest research reports is helpful to further understand the relationship between the structure， biological activity， and functional application of natural arabinogalactan and provides an important reference for future research and development.

BACKGROUND:Repetitive trans-spinal magnetic stimulation(rTSMS)can inhibit inflammatory responses following spinal cord injury.rTSMS applies magnetic field stimulation to the spinal cord region to modulate neuronal excitability and synaptic transmission,thereby promoting plasticity and repair of the nervous system. OBJECTIVE:To observe the effects of rTSMS on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB/NLRP3 signaling pathway after spinal cord injury and explore its mechanism in promoting motor function recovery. METHODS:Male C57BL/6J mice,SPF grade,were randomly divided into sham surgery group,spinal cord injury group,and rTSMS group.The latter two groups of mice were anesthetized and the T9 vertebral plate was removed using rongeur forceps to expose the spinal cord,and the spinal cord was clamped using a small aneurysm clip for 20 seconds to establish the spinal cord injury model.Mice in the rTSMS group underwent a 21-day rTSMS intervention starting on day 1 after spinal cord injury.The stimulation lasted 10 minutes per day,5 days per week with an interval of 2 days.Basso Mouse Scale scores were used to assess motor function recovery in mice after spinal cord injury at 1,3,7,14,and 21 days after spinal cord injury.Western blot was employed to detect the expression of AQP4,apoptotic factors Bax,Bcl-2,CL-Caspase-3,inflammatory factors tumor necrosis factor-α,interferon-γ,interleukin-6,interleukin-4,and the TLR4/NF-κB/NLRP3 signaling pathway related proteins in the injured spinal cord.Oxidative stress assay kit was used to measure the activity of superoxide dismutase,glutathione peroxidase,and malondialdehyde content at the site of spinal cord injury.Immunofluorescence staining was performed to detect the expression of neuronal nuclei(NeuN). RESULTS AND CONCLUSION:The Basso Mouse Scale score in the rTSMS group was significantly higher than that in the spinal cord injury group(P<0.05).Compared with the spinal cord injury group,the rTSMS group showed a reduction in spinal cord water content.The expression of AQP4 protein,malondialdehyde content,and expression of Bax,Bcl-2,CL-Caspase-3,tumor necrosis factor-α,interferon-γ,interleukin-6,and TLR4/NF-κB/NLRP3 signaling pathway related proteins were all decreased in the rTSMS group,while the activities of superoxide dismutase and glutathione peroxidase,as well as the expression of Bcl-2,interleukin-4,and NeuN,were all increased(P<0.05).These results suggest that rTSMS downregulates the expression of proteins related to the TLR4/NF-κB/NLRP3 signaling pathway,alleviating symptoms after spinal cord injury such as spinal cord edema,oxidative stress,apoptosis,and inflammation,exerting neuroprotective effects,and thereby promoting the recovery of hindlimb motor function after spinal cord injury.

ObjectiveTo investigate the mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer by observing the effects of Buzhong Yiqitang on endoplasmic reticulum stress-related molecules in human lung adenocarcinoma cells （A549） and cisplatin-resistant cells in human lung adenocarcinoma cells （A549/DDP） via the nuclear factor E₂-related factor 2（Nrf2）/reactive oxygen species（ROS） pathway. MethodsThe serum containing Buzhong Yiqitang was prepared and A549 cells and A549/DDP cells were cultured. The cells were randomized into groups A （A549 cells+blank serum）， B （A549 cells+20 mg·L^-1 cisplatin+blank serum）， C （A549 cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）， D （A549/DDP cells+blank serum）， E （A549/DDP cells+20 mg·L^-1 cisplatin+blank serum）， and F （A549/DDP cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）. The cell counting kit-8 （CCK-8） method was used to detect the half maximal inhibitory concentration （IC₅₀） of cisplatin. The protein levels of Nrf2 and p-Nrf2 were determined by Western blotting. The DCFH-DA fluorescent probe was used to measure the content of reactive oxygen species （ROS） in each group. The protein levels of glucose-regulated protein 78 （GRP78）， activated transcription factor 6 （ATF6）， and C/EBP-homologous protein （CHOP） were determined by Western blot. ResultsCompared with group B， group C showed a reduction in IC₅₀ of cisplatin （P<0.05）， which held true in group E compared with group F （P<0.05）. Moreover， the IC₅₀ of cisplatin to A549/DDP cells was higher than that to A549 cells before and after Buzhong Yiqitang intervention （P<0.05）. Compared with group A， group B showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group B， group C showed down-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group D， group E showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）， which， however， were significantly down-regulated in group F （P<0.05）. The ROS content and the protein levels of GRP78， ATF6， and CHOP followed a descending trend of group C > group B > group A in A549 cells and group F > group E > group D in A549/DDP cells （P<0.05）. Moreover， the ROS content and the protein levels of GRP78， ATF6， and CHOP in A549 cells were higher than those in A549/DDP cells before and after Buzhong Yiqitang intervention （P<0.05）. ConclusionBuzhong Yiqitang may regulate endoplasmic reticulum stress via the Nrf2/ROS pathway to attenuate cisplatin resistance in non-small cell lung cancer.

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

OBJECTIVE: It has been reported that the mRNA expression of serine protease 23 (PRSS23) was increased in skin fibroblasts from systemic sclerosis patients (SSc). The purpose of this study is to explore the pathogenetic effect and mechanism of PRSS23 in skin fibrosis of SSc. METHODS: The expression of PRSS23 in skin tissues from the SSc patients and healthy controls was detected by immunohisto-chemistry. Fibroblasts isolated from fresh skin tissue were used to detect the expression of PRSS23 by real-time quantitative PCR (RT-qPCR) and Western blot. Overexprssion of PRSS23 in BJ, the fibroblasts cell line of skin, was constructed by lentivirus. After stimulation with 400 μmol/L hydrogen peroxide for 12 h, Annexin V/7-AAD staining was used to detect apoptosis of fibroblasts; flow cytometry and Western blot were used to detect the expression of apoptosis-related protein cleaved Caspase-3. The expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in fibroblasts was detected by RT-qPCR and enzyme linked immunosorbent assay (ELISA). RESULTS: Compared with the healthy controls, the expression of PRSS23 in skin tissues of the SSc patients was significantly increased [4.952 (3.806-5.439) vs. 0.806 (0.395-1.173), P < 0.001], and fibroblast was the main cell that expressed PRSS23. The mRNA [27.59 (25.02-30.00) vs. 1.00, P < 0.001] and protein [0.675 (0.587-0.837) vs. 0.451 (0.342-0.502), P=0.029] of PRSS23 in skin fibroblasts isolated from the SSc patients were significantly up-regulated. Compared with the control group, the anti-apoptotic ability of skin fibroblasts overexpressing PRSS23 was enhanced, and the proportion of apoptotic cells was significantly reduced after hydrogen peroxide induction [(5.043±1.097)% vs. (17.480±3.212)%, P=0.022], the expression of apoptosis-related protein cleaved Caspase-3 was also markedly reduced [(0.718±0.022) vs. (1.422±0.105), P=0.003]. In addition, the mRNA [(99.780±1.796) vs. (1.000±0.004), P < 0.001] and protein [(211.600±2.431) ng/L vs. (65.930±1.768) ng/L, P < 0.001] of IL-6 in the fibroblasts overexpressing PRSS23 were significantly up-regulated; the mRNA[(3.555±0.555) vs. (1.000±0.004), P < 0.001] and protein levels [(41.190±0.949) ng/L vs. (31.150±0.360) ng/L, P < 0.001] of TNF-α in the fibroblasts overexpressing PRSS23 were also significantly up-regulated. CONCLUSION The expression of PRSS23 is increased in skin fibroblasts of SSc patients. PRSS23 can inhibit cell apoptosis, promote the secretion of inflammatory factors such as IL-6 and TNF-α, and regulate the process that skin fibroblasts transform into pro-inflammatory type. So, PRSS23 is associated with the development of skin fibrosis.
Humans ; Scleroderma, Systemic/enzymology* ; Fibroblasts/pathology* ; Apoptosis ; Skin/metabolism* ; Fibrosis ; Interleukin-6/metabolism* ; Caspase 3/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Male ; Female ; Cells, Cultured ; RNA, Messenger/metabolism* ; Middle Aged ; Adult ; Serine Endopeptidases/genetics*

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Objective To investigate the effects of high-risk human papillomavirus 16 E6 protein(HPV16 E6 protein)on invasion and migration of cervical cancer SiHa cells via regulating the expression of expression miR-23a.Methods Tissue samples from 100 patients with cervical cancer HPV-negative,100 HPV-positive patients,and 100 paracancerous normal tissues were collected;cervical cancer SiHa cells were divided into blank group,E6 overexpression group,negative transfection group,and E6 + miR-23a mimics group.The expression of miR-23a and HPV16 E6 mRNA were detected by qRT-PCR;MTT assay was used to detect the cell proliferation inhibition rate;flow cytometry to detect the apoptosis;Transwell chamber assay to detect cell invasion,and scratch test to detect the ability of cell migration.The expression of HPV16 E6,apoptosis related proteins(Caspase-3,Bax,Bcl-2),and migration related proteins(MMP-2,MMP-9)was detected by WB.Results The expression level of miR-23a was decreased in cervical cancer tissues,and that was lower in HPV positive cervical cancer tissues.Overexpression of E6 decreased the expression level of miR-23a,cell proliferation inhibition rate,apoptosis rate,Caspase-3 and Bax protein expression,and increased the expression of Bcl-2 protein,scratch healing rate,inva-sion cell number,MMP-2,MMP-9 protein expression(P<0.05);miR-23a mimics reversed the effects of E6 overexpression on the above indicators.Conclusion HPV16 E6 promotes the invasion and migration of cervical cancer cells,which may be related to the regulation of miR-23a expression.

The online and offline hybrid teaching model of evidence-based medicine (EBM) is currently in the stage of development. Previous teaching focused on the teaching process in the classroom, and did not organically combine all the course contents before, during, and after class. The BOPPPS model can be used to establish coherence and integrity in the EBM teaching process. Considering the discipline characteristics and teaching objectives of EBM, this study initially explored and designed a BOPPPS-based online and offline hybrid teaching model. Taking the "diagnostic evidence" module as an example, the teaching implementation details were introduced. A pre-designed questionnaire was used to conduct baseline survey and follow-up survey on students before and after class to evaluate the teaching model and effect. The surveys showed that half of the students (77/154) preferred the new online and offline hybrid teaching model of EBM. The students found that all aspects of BOPPPS teaching were generally acceptable and satisfactory. Compared with before teaching, the students' proficiency in EBM was significantly improved after the teaching ( P<0.001), particularly in their ability to retrieve literature and evaluate the quality of evidence, which is of great significance for expanding their knowledge and clinical thinking.

Objective To evaluate the effect of photo-activated disinfection(PAD)as a kind of adjuvant treatment on moderate to severe chronic periodontitis.Methods 21 patients with the chronic periodontitis(totally 218 selected sites)were randomly enrolled and divided into group A(minocycline hydrochloride),group B(PAD),group C(PAD + minocycline hydrochloride),and group D(no adjunctive therapy)for the adjunctive treatment after receiving the scaling and root planing(SRP).Periodontal indexs as probing depth(PD),bleeding on probing(BOP)and clinical attachment loss(CAL)were examined at the baseline,6 and 12 weeks after the treatment.Meanwhile,periodontal pathogens as Porphyromonas gingivalis(Pg)and Tannerella forsythia(Tf)from subgingival plaque of group A,B and C were detected by Real-time PCR.Results Compared with the baseline,the periodontal inflammations of all groups were improved signiffcantly at 6 and 12 weeks after the treatment(P<0.001),and group A,group B and group C were better than group D(P<0.001),group C was better than group A(P<0.001);Furthermore,the concentration of Pg and Tf was decreased significantly(P<0.001),and there was no difference among the three groups with adjunctive therapy.Conclussion As the adjunctive treatment of SRP,PAD could achieve the same and even better effect than minocycline hydrochloride ointment.