Stem-leaf saponins from Panax notoginseng (SLSP) comprise numerous PPD-type saponins with diverse pharmacological properties; however, their role in Parkinson's disease (PD), characterized by microglia-mediated neuroinflammation, remains unclear. This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models, including the 1-methyl-4-phenylpyridinium (MPTP)-induced mouse model and lipopolysaccharide (LPS)-stimulated BV-2 microglia. Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD, including MPTP-treated mice. Additionally, SLSP inhibited the upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX2) and attenuated the phosphorylation of PI3K, protein kinase B (AKT), nuclear factor-κB (NFκB), and inhibitor of NFκB protein α (IκBα) both in vivo and in vitro. Moreover, SLSP suppressed the production of inflammatory markers such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha (TNF-α) in LPS-stimulated BV-2 cells. Notably, the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPS-treated BV-2 cells. These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models, likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway. These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
Animals ; Panax notoginseng/chemistry* ; Saponins/pharmacology* ; Microglia/immunology* ; Mice ; NF-kappa B/immunology* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/genetics* ; Male ; Parkinson Disease/immunology* ; Mice, Inbred C57BL ; Disease Models, Animal ; Plant Leaves/chemistry* ; Neuroinflammatory Diseases/drug therapy* ; Humans

Objective To estimate the flexion and extension torques of the hip,knee,and ankle joints during straight-line walking using depth cameras and neural networks.Methods Gait information was collected from 20 individuals using an optical motion capture system,force plates,and an Azure Kinect depth camera.The subjects were asked to walk straight at their preferred speed while stepping on the force plates.The joint torques were obtained using visual 3D simulation as a reference value,and an artificial neural network(ANN)and long short-term memory(LSTM)network were trained to estimate the joint torques.Results The relative root mean square errors(rRMSEs)of the ANN model for estimating the joint torques of hip,knee,and ankle were 15.87％-17.32％,18.36％-25.34％,and 14.11％-16.82％,respectively,and the correlation coefficients were 0.81-0.85,0.69-0.74 and 0.76-0.82,respectively.The LSTM model had a better estimation effect,with rRMSEs of 8.53％-12.18％,14.32％-18.78％,and 6.51％-11.83％,and correlation coefficients of 0.89-0.95,0.85-0.91 and 0.90-0.97,respectively.Conclusions This study confirms the feasibility of using a depth camera and neural network for noncontact estimation of lower limb joint torques,and LSTM has a better performance.Compared with existing studies,the joint torque estimation results have better accuracy,and the potential application scenarios include telemedicine,personalized rehabilitation program development,and orthosis-assisted design.

Irinotecan (CPT11) chemotherapy-induced diarrhea affects a substantial cancer population due to β-glucuronidase (Gus) converting 10-O-glucuronyl-7-ethyl-10-hydroxycamptothecin (SN38G) to toxic 7-ethyl-10-hydroxycamptothecin (SN38). Existing interventions primarily address inflammation and Gus enzyme inhibition, neglecting epithelial repair and Gus-expressing bacteria. Herein, we discovered that dehydrodiisoeugenol (DDIE), isolated from nutmeg, alleviates CPT11-induced intestinal mucositis alongside a synergistic antitumor effect with CPT11 by improving weight loss, colon shortening, epithelial barrier dysfunction, goblet cells and intestinal stem cells (ISCs) loss, and wound-healing. The anti-mucositis effect of DDIE is gut microbiota-dependent. Analysis of microbiome profiling data from clinical patients and CPT11-induced mucositis mice reveals a strong correlation between CPT11 chemotoxicity and Gus-expressing bacteria, particularly Enterococcus faecalis (E. faecalis). DDIE counters CPT11-induced augmentation of E. faecalis, leading to decreased intestinal Gus and SN38 levels. The Partial Least Squares Path Model (PLS-PM) algorithm initially links E. faecalis to dysregulated epithelial renovation. This is further validated in a 3D intestinal organoid model, in which both SN38 and E. faecalis hinder the formation and differentiation of organoids. Interestingly, colonization of E. faecalis exacerbates CPT11-induced mucositis and disturbs epithelial differentiation. Our study unveils a microbiota-driven, epithelial reconstruction-mediated action of DDIE against mucositis, proposing the 'Gus bacteria-host-irinotecan axis' as a promising target for mitigating CPT11 chemotoxicity.

OBJECTIVE: To determine whether miRNA-128-3p regulates malignant biological behavior of glioma cells by targeting KLHDC8A. METHODS: Dual-luciferase reporter assays, qRT-PCR and Western blotting were used to verify the targeting of miRNA-128-3p to KLHDC8A. Edu assay, flow cytometry, Transwell assay and would healing assay were used to determine the effects of changes in miRNA-128-3p and KLHDC8A expression levels on malignant behavior of glioma cells. Rescue experiment was carried out to verify that miRNA-128-3p regulated glioma cell proliferation, apoptosis, invasion and migration by targeting KLHDC8A. RESULTS: The expression level of KLHDC8A was significantly increased in high-grade glioma tissue and was closely related to a poor survival outcome of the patients. Overexpression of KLHDC8A promoted glioma cell proliferation, migration and invasion, and miRNA-128-3p overexpression inhibited proliferative and metastatic capacities of glioma cells. Mechanistically, KLHDC8A expression was directly modulated by miRNA-128-3p, which, by targeting KLHDC8A, inhibited malignant behavior of glioma cells. CONCLUSION Upregulation of miRNA-128-3p inhibits uncontrolled growth of glioma cells by negatively regulating KLHDC8A expression and its downstream effectors, suggesting that the miRNA-128-3p-KLHDC8A axis may serve as a potential prognostic indicator and a therapeutic target for developing new strategies for glioma treatment.
Humans ; Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioma/pathology* ; MicroRNAs/metabolism* ; Up-Regulation

Solid pseudopapillary neoplasm of the pancreas (SPN) is a rare pancreatic tumor with low-grade malignancy. Surgical resection is the preferred therapeutic approach for SPN patients, which has favourable prognosis with extremely low incidence of recurrence and metastasis and 5-year survival rate as 95%. With the improvement of radiological and pathological diagnosis, the detection rate of SPN is increasing. However, its pathogenesis is still unclear. Meanwhile, the diagnostic criteria and treatment strategies of SPN require standardization. Herein, the authors review the current status and advances in SPN based on related literature and clinical experience of the authors′ team on treatment of SPN, in order to deepen the knowledge of SPN, improve the ability for the preoperative diagnosis, promote standardized treatment and maximize benefits of the patients.

Objective To observe the effect of different temperatures on endoplasmic reticulum stress, calcium overload, mitochondria and cell damage in pulmonary microvascular endothelial cells (PMVEC) induced by heat stress, and clarify the mechanism of endothelial cell injury in the process of heat stress to provide experimental basis for clinical prevention and treatment of heat stree. Methods Heat stress model of PMVEC cell was set up. Control group cells were incubated at 37℃, 5%CO2, while heat stress group cells were incubated at 39℃, 41℃, 43℃ for 2h, respectively, then further incubated at 37℃, 5%CO2 for 6h. Pretreatment of cells with 20μmol/L BAPTA-AM or 50μmol/L CsA before heat stress at 43℃. The protein levels of p-PERK, PERK p-eIF2a, eIF2a, ATF4 and GRP78 were analyzed by Western blotting. Intracellular Ca2+, mitochondrial membrane potential and the changes in mitochondrial permeability transition pore were investigated by flow cytometry. The change of caspase-3 was detected by Caspase Assay Kit. Millicell-ERS Volt-Ohm Meter and Accessories was used for determining the changes of transepithelium electrical resistance (TER). Results Compared with the control group, with the increase of heat stress temperature (41-43℃), the phosphorylation of p-PERK and p-eIF2a protein and the expressions of ATF4 and GRP78 proteins were gradually activated, intracellular Ca2+ increased, MPTP pore was opened, mitochondrial membrane potential decreased, cell permeability increased and apoptosis occurred, and it was the most obvious in the 43℃ heat stress group, and the difference was statistically significant (P<0.05). Pretreatment with Ca2+ inhibitors promoted the recovery of the MPTP hole, mitochondrial membrane potential and cell permeability, and reduced the occurrence of apoptosis. While pretreatment with the mitochondrial protective agent did not reduce the release of Ca2+, but it could promote the recovery of cell permeability and reduce the occurrence of apoptosis. Conclusion Heat stress activates endoplasmic reticulum stress response, induces intracellular Ca2+ overload mediated cell and mitochondrial damages in PMVEC cells, which may be one of the important mechanisms of endothelial cell injury induced by heat stress.

OBJECTIVE To explore the effect and mechanisms of baicalein on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis in mice.METHODS BALB/c mice were randomly placed into three groups (n=10):normal control group,TNBS group,and TNBS+baicalein (20 mg· kg-1,once per day) group.Mouse colitis was induced by intrarectal injection of TNBS.Baicalein was administered by oral gavage two days prior to TNBS treatment and until the end of the study (a total of 9 d).The colon length was measured before HE staining was performed for histological damage assessment.The remaining colon pieces were collected to measure the content of tumor necrosis factor-α(TNF-α).Lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophage was used as a cell model to determine the content of nitric oxide (NO) in cell culture medium,the mRNA levels of TNF-α,interleukin-6(IL-6),IL-1β,inducible nitric oxide synthase(iNOS),cyclooxygenase 2(COX-2) and monocyte chemoattractant protein-1 (MCP-1),and the protein expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB (PI3K/AKT/NF-κB) pathway.RESULTS Baicalein significantly attenuated TNBS-induced colon shortening and histological injury (P＜0.05),which was correlated with the decline in the content of TNF-α in the colon.According to the jn vivo results,baicalein exposure down-regulated the secretion of NO and the mRNA expression of pro-inflammatory mediators (iNOS,COX-2,MCP-1,TNF-α,IL-1β and IL-6) in LPS-stimulated RAW264.7 cells (P＜0.05,P＜0.01).Additionally,the phosphorylation/activation of LPS-stimulated PI3K/AKT/NF-κB pathway was inhibited by baicalein treatment.CONCLUSION The beneficial effect of baicalein in TNBS-induced experimental colitis may be due to PI3K/AKT/NF-κB signaling inhibition.

In order to meet the requirements of ultrasound bone density measurement, we proposed a software solution to improve the accuracy and speed of measurement of bone mineral density of the ultrasound bone densitometer. We used a high-speed USB interface chip FT232H, along with a high-speed AD converter chip to calculate speed of sound (SOS), broadband ultrasound attenuation (BUA ) and other bone density parameters in the PC software. This solution improved the accuracy of the measurement data, reduced the measurement time and increased the quality of the displayed image. It is well concluded that the new software can greatly improve the accuracy and transmission speed of bone density measurement data through a high-speed USB interface and a software data processing technology.
Absorptiometry, Photon ; Bone Density ; Software ; Sound ; Ultrasonics

OBJECTIVETo observe the effect of traditional Chinese medicine formulas clearing away heat and promoting blood circulation-Biejiayinzi (BJYZ), Gexiazhuyu Tang (GXZYT) and Fugan Wan (FGW) on liver fibrosis in CCl4 mice by screening and analyzing formula-syndrome database of kidney and liver fibrosis based on the principle of formula-syndrome, compared with pivot-harmonizing decoction.

METHODTen-week-old male C57BL/6 mice, with the weight of (20 +/- 3) g, were randomly divided into 6 groups: the normal group, the model group, the BJYZ group, the GXZY group, the FGW group and the XST group. Except the normal group, other groups were abdominally injected with 10% CCl4 olive oil solution a dose of 2 mL x kg(-1) body weight for four weeks, three times each week. Meanwhile, the latter four groups were administered with extracts of BJYZ, GXZYT, FGW and XST, respectively, once every day, concomitantly continued CCl4 administration. The normal and the model groups were given the same volume of deionized water. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gamma-GT), Alb and TBil were detected by chemiluminescence. The hydroxyproline (HYP) content was detected by acid hydrolysis method. The hepatic collagen deposition was evaluated with Sirius red staining.

RESULTCompared with the normal group, the model group recorded notable decrease in weight and increase in the ratio of liver weight and body weight and the ratio of spleen weight and body weight, with obvious fatty degeneration and inflammatory necrosis in liver cells. Collagen fiber deposition was so notable to form fibrous septums and pseudolobules. The levels of serum ALT, AST, TBil, gamma-GT, the HYP content in liver tissue and the deposition of hepatic collagen were significantly increased in the model group. Compared with model group, Serum AST were significantly decreased in BJYZ group as gamma-GT decreased in the GXZYT group, without notable decrease in degeneration and inflammatory necrosis in liver cells and collagen deposition. The GXZYT group showed significant decrease in gamma-GT, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The ratio of liver weight and body weight, AST, gamma-GT and HYP content were significantly decreased in the FGW group, with slight improvement in degeneration and inflammatory necrosis in liver cells and reduction in collagen deposition. The XST group showed decrease in the ratio of liver weight and body weight, with no obvious change in inflammation and fibrosis of hepatic tissue.

CONCLUSIONFGW shows the best effect of prevention and treatment of liver fibrosis in CCl4 mice.

Animals ; Blood Circulation ; drug effects ; Body Temperature ; drug effects ; Carbon Tetrachloride ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Hydroxyproline ; metabolism ; Liver ; drug effects ; metabolism ; pathology ; Liver Cirrhosis ; drug therapy ; metabolism ; pathology ; prevention & control ; Male ; Mice ; Mice, Inbred C57BL ; Organ Size ; drug effects

Based on the approaches of TLC identification, HPLC for assaying managiferin, and of the determination of water, total ash and acid-insoluble ash in 12 samples, collected from southwest of China, the quality standard of Gentiana rhodantha has been established. The results show the reference materia medica and mangiferin can be both well used as reference substances for TLC identification; the mass fractions of mangiferin is 0.7%-4.4% (average 2.8%), water 6.1%-8.6% (average 7.2%), total ash 3.7%-10.8% (average 6.6%) and acid-insoluble ash 0.2%-2.7% (average 1.3%). The recommended standards of quantitative indexes are that the mass fractions of mangiferin is not less than 2.0%, and the water, total ash and acid-insoluble ash are not more than 9.0%, 8.0% and 3.0% respectively.
Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Drugs, Chinese Herbal ; analysis ; Gentiana ; chemistry ; Reproducibility of Results