Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P＜0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P＜0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

With the rapid development of social economy and the continuous improvement of human living standard, the incidence, fatality and recurrence rates of cardiovascular disease (CVD) are increasing year by year, which seriously affects people's life and health. Conventional therapeutic drugs have limited improvement on the disability rate, so the search for new therapeutic drugs and action targets has become one of the hotspots of current research. In recent years, the therapeutic role of the natural compound rosmarinic acid (RA) in CVD has attracted much attention, which is capable of preventing CVD by modulating multiple signalling pathways and exerting physiological activities such as antioxidant, anti-apoptotic, anti-inflammatory, anti-platelet aggregation, as well as anti-coagulation and endothelial function protection. In this paper, the role of RA in the prevention of CVD is systematically sorted out, and its mechanism of action is summarised and analysed, with a view to providing a scientific basis and important support for the in-depth exploration of the prevention value of RA in CVD and its further development as a prevention drug.

Objective To investigate the protective effect of astaxanthin(ASTA)on gouty chondrocyte injury induced by monosodium urate crystal(MSU)and its mechanism.Methods The gout cell model by sodium urate crystals was established.C-28I2 cells were randomly divided into blank group(conventional culture),model group(200 μg·mL-1MSU),experimental-L group(200 μg·mL-1 MSU+20 μmol·mL-1 ASTA),experimental-H group(200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+Vector group(transfected with Vector+200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+NLRP3 group(transfected with NLRP3 plasmid+200 ig·mL-1 MSU+40 μmol·L-1 ASTA).Cell counting kit-8(CCK-8)assay was used to detect the cell proliferation rate;Western blot assay was used to detect the expression of related proteins;the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay(ELISA).Results The cell proliferation rate of blank group,model group,experimental-L group and experimental-H group were(100.00±5.40)％,(67.41±4.52)％,(72.69±5.05)％and(81.47±7.73)％,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group(all P＜0.05).Nucleotide binding oligomeric domain-like receptor protein 3(NLRP3)protein expression levels in blank group,model group,experimental-L group,experimental-H group,experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04,0.86±0.06,0.72±0.10,0.52±0.03,0.51±0.03 and 1.13±0.10,respectively;the expression levels of cleaved Caspase-1(Cl-caspase-1)protein were 0.33±0.05,0.73±0.08,0.61±0.07,0.42±0.04,0.39±0.04 and 0.70±0.06,respectively;the mature interleukin(m-IL)-1 β protein expression levels were 0.26±0.03,0.91±0.05,0.70±0.11,0.57±0.08,0.58±0.06 and 0.79±0.08,respectively;the Hyp levels were(1.95±0.22),(3.33±0.25),(2.53±0.18),(2.22±0.21),(2.24±0.20)and(3.25±0.38)μg·mL-1,respectively;the GAG levels were(2.30±0.20),(3.71±0.26),(3.29±0.33),(2.90±0.16),(2.97±0.24)and(3.50±0.34)ng·mL-1,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group,between the experimental-H+NLRP3 group and the experimental-H+Vector group(all P＜0.05).Conclusion Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Objective To investigate the protective effect of astaxanthin(ASTA)on gouty chondrocyte injury induced by monosodium urate crystal(MSU)and its mechanism.Methods The gout cell model by sodium urate crystals was established.C-28I2 cells were randomly divided into blank group(conventional culture),model group(200 μg·mL-1MSU),experimental-L group(200 μg·mL-1 MSU+20 μmol·mL-1 ASTA),experimental-H group(200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+Vector group(transfected with Vector+200 μg·mL-1 MSU+40 μmol·L-1 ASTA),experimental-H+NLRP3 group(transfected with NLRP3 plasmid+200 ig·mL-1 MSU+40 μmol·L-1 ASTA).Cell counting kit-8(CCK-8)assay was used to detect the cell proliferation rate;Western blot assay was used to detect the expression of related proteins;the levels of Hyp and GAG were detected by enzyme-linked immunosorbent assay(ELISA).Results The cell proliferation rate of blank group,model group,experimental-L group and experimental-H group were(100.00±5.40)％,(67.41±4.52)％,(72.69±5.05)％and(81.47±7.73)％,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group(all P＜0.05).Nucleotide binding oligomeric domain-like receptor protein 3(NLRP3)protein expression levels in blank group,model group,experimental-L group,experimental-H group,experimental-H+Vector group and experimental-H+NLRP3 group were 0.44±0.04,0.86±0.06,0.72±0.10,0.52±0.03,0.51±0.03 and 1.13±0.10,respectively;the expression levels of cleaved Caspase-1(Cl-caspase-1)protein were 0.33±0.05,0.73±0.08,0.61±0.07,0.42±0.04,0.39±0.04 and 0.70±0.06,respectively;the mature interleukin(m-IL)-1 β protein expression levels were 0.26±0.03,0.91±0.05,0.70±0.11,0.57±0.08,0.58±0.06 and 0.79±0.08,respectively;the Hyp levels were(1.95±0.22),(3.33±0.25),(2.53±0.18),(2.22±0.21),(2.24±0.20)and(3.25±0.38)μg·mL-1,respectively;the GAG levels were(2.30±0.20),(3.71±0.26),(3.29±0.33),(2.90±0.16),(2.97±0.24)and(3.50±0.34)ng·mL-1,respectively.The above indicators showed statistically significant differences between the model group and the blank group,between the experimental-L,experimental-H groups and the model group,between the experimental-H+NLRP3 group and the experimental-H+Vector group(all P＜0.05).Conclusion Astaxanthin can regulate NLRP3 to play an anti-inflammatory role and has a protective effect on MSU-induced gouty cartilage injury.

Paclitaxel(PTX)is a first-line chemotherapy drug for breast cancer,but its resistance issues significantly impact clinical treatment efficacy.Fucosylation,especially core fucosylation,is closely related to tumor chemoresistance,resulting in poor chemotherapy responses and poor prognosis in patients.In this study,we investigated the effect and mechanism of the fucosylation inhibitor 2-fluorofucose(2-F-Fuc)on the chemosensitivity of paclitaxel-resistant breast cancer MCF-7/PTX cells.The drug resistanceindex(RI)of MCF-7/PTX cells was 8.49 by MTT assays.Western blotting,real-time PCR,enzyme-linked immu-nosorbent assay(ELISA)and Lens Culinaris Agglutinin(LCA)lectin imprinting showed that compared with MCF-7 cells,the expression of FUT8,MDR1and core fucosylation in MCF-7/PTX cells was high.Western blotting showed that 2-F-Fuc had a significant inhibitory effect on the growth of MCF-7/PTX cells,and the expression levels of FUT8 and MDR1 were significantly down-regulated after 2-F-Fuc treatment,and the down-regulation was more pronounced in the PTX and 2-F-Fuc combination group(P＜0.05).Compared to the control,expression of PCNA in MCF-7/PTX cells in the PTX and the 2-F-Fuc group were down-regulated,and the apoptosis-related proteins,such as cleaved caspase-3 and Bax/Bcl-2 were in-creased.The level of p-PI3K and p-AKT were down-regulated,and the changes in the combination of 2-F-Fuc and PTX were more robust(P＜0.05).The above results showed that the core fucosylation level of MCF-7/PTX cells was significantly increased,and 2-F-Fuc could reduce the core fucosylation level of MCF-7/PTX cells by inhibiting the expression of FUT8,and enhance the sensitivity of drug-resistant cells to PTX,which may correlate with the downregulation of PI3K/AKT signaling pathway proteins.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Objective:To investigate the role of ezrin-radixin-moesin-binding phosphoprotein 50 (EBP50) in renal tubular epithelial-mesenchymal transition (EMT) in diabetic nephropathy (DN).Methods:Renal tissue specimens from 24 DN patients (DN group) confirmed by medical history, clinical laboratory tests, and pathological diagnosis at the Third Hospital of Hebei Medical University and 15 adjacent normal renal tissues (control group) from 2018 to 2023 were collected. Immunohistochemical staining was performed to detect the expression of EBP50, E-cadherin, and Vimentin proteins. Additionally, 10 healthy volunteers were enrolled as a normal group, and fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were compared between DN patients and the normal group.Results:Fasting blood glucose, serum creatinine, blood urea nitrogen, and 24 h urinary protein levels were significantly higher in the DN group than in the normal group (all P<0.01). Periodic acid-schiff (PAS) staining revealed significant thickening of the glomerular basement membrane, increased extracellular matrix, vacuolar degeneration of renal tubules, and elevated extracellular matrix in the renal interstitium in the DN group. Immunohistochemistry showed higher expression of EBP50 and E-cadherin proteins in the control group than in the DN group (all P<0.01), while Vimentin expression was lower in the control group ( P<0.01). Conclusions:EBP50 is involved in the EMT process of renal tubules in DN and is associated with tubular injury.

Objective To investigate the expression of MutS homolog 3(MSH3)in oral squamous cell carcinoma and its significance.Methods The MSH3 protein expression was examined by immunohistochemistry in 20 normal oral mucosa and 60 oral squamous cell carcinoma tissues.Results Our results showed that MSH3 expression in oral squamous cell carcinoma tissues was lower than normal oral mucosa.The MSH3 expression in oral squamous cell carcinoma tissues with better differentiation was higher than that with worse differentiation.The positive MSH3 expression decreased from oral squamous cell carcinoma patients without lymph nodal metastasis to that with metastasis.MSH3 expression was not related to the patients'gender,age,tumour location or size.Conclusion Downregulation of MSH3 is consistent with poorly differentiation and nodal metastasis in oral squamous cell carcinoma.MSH3 may play a significant role in the malignant progression of oral squamous cell carcinoma.

Objective To explore the effect of CircCSNK1G1 on the proliferation,apoptosis and migration of gastric cancer(GC)cells by regulating the miR-381-3p/S kinase-related protein 2(Skp2)axis.Methods HGC-27 cells were divided into non transfected group,si-NC group,si-CircCSNK1G1 group,si-CircCSNK1 G1+anti-miR-NC group,and si-CircCSNK1G1+anti-miR-381-3p group.The expressions of CircCSNK1G1,miR-381-3p and Skp2 mRNA in GC tumor tissues and GC cell lines were detected by qRT-PCR respectively;cell proliferation was detected by MTT assay;the number of cell clones was detected by clonogenic assay;apoptosis was detected by flow cytometry;cell migration and invasion ability were determined by transwell;the expression of E-cadherin and Vimentin was detected by Western Blot;and the targeting relationship among CircCSNK1G1,miR-381-3p and Skp2 was verified by double luciferase experiment.Results Compared with GES-1 in normal tissues adjacent to cancer and normal human gastric mucosal epithelial cells,the expression of CircCSNK1 G1 and Skp2 mRNA in GC tumor tissues and GC cell lines is high,and the expression of miR-381-3p is low(P＜0.05),and the expression level of miR-381-3p in HGC-27 cells is the lowest,and the expression level of CircCSNK1G1 and Skp2 mRNA is the highest,therefore,HGC-27 cells were selected and CircCSNK1G1 was knocked down for the experiment.Compared with untransfected group and si-CircCSNK1G1-NC group,transfection of si-CircCSNK1G1 could reduce the expression of CircCSNK1G1,Skp2 mRNA,cell proliferation activity,cell migration number,and the expression of Vimentin protein in HGC-27 cells(P＜0.05),the expression of miR-381-3p,apoptosis rate,and the expression of E-cadherin protein were increased(P＜0.05).The double luciferase experiment verified that CircCSNK1G1 and Skp2 had a targeting relationship with miR-381-3p,moreover,CircCSNK1G1 could be used as sponge RNA of miR-381-3p to further regulate the expression and activity of Skp2.Conclusion Knockdown of CircCSNK1G1 can target up-regulate the expression of miR-381-3p,and inhibit the expression of Skp2,thus promoting the apoptosis of GC cells,and inhibiting their proliferation and migration.