OBJECTIVE: To evaluate the protective effects of gentiopicroside (GPS) against reactive oxygen species (ROS)-induced NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation in endothelial cells, aiming to reduce atherosclerosis. METHODS: Eight-week-old male ApoE-deficient mice were randomly divided into 2 groups (n=10 per group): the vehicle group and the GPS treatment group. Both groups were fed a high-fat diet for 16 weeks. GPS (40 mg/kg per day) was administered by oral gavage to the GPS group, while the vehicle group received an equivalent volume of the vehicle solution. At the end of the treatment, blood and aortic tissues were collected for assessments of atherosclerosis, lipid profiles, oxidative stress, and molecular expressions related to NLRP3 inflammasome activation, ROS production, and apoptosis. Additionally, in vitro experiments on human aortic endothelial cells treated with oxidized low-density lipoprotein (ox-LDL) were conducted to evaluate the effects of GPS on NLRP3 inflammasome activation, pyroptosis, apoptosis, and ROS production, specifically examining the role of the sirtuin 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. SIRT1 and Nrf2 inhibitors were used to confirm the pathway's role. RESULTS: GPS treatment significantly reduced atherosclerotic lesions in the en face aorta (P<0.01), as well as in the thoracic and abdominal aortic regions, and markedly decreased sinus lesions within the aortic root (P<0.05 or P<0.01). Additionally, GPS reduced oxidative stress markers and proinflammatory cytokines, including interleukin (IL)-1 β and IL-18, in lesion areas (P<0.05, P<0.01). In vitro, GPS inhibited ox-LDL-induced NLRP3 activation, as evidenced by reduced NLRP3 (P<0.01), apoptosis-associated speck-like protein containing a CARD, cleaved-caspase-1, and cleaved-gasdermin D expressions (all P<0.01). GPS also decreased ROS production, apoptosis, and pyroptosis, with the beneficial effects being significantly reversed by SIRT1 or Nrf2 inhibitors. CONCLUSION GPS exerts an antiatherogenic effect by inhibiting ROS-dependent NLRP3 inflammasome activation via the SIRT1/Nrf2 pathway.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Reactive Oxygen Species/metabolism* ; Iridoid Glucosides/therapeutic use* ; NF-E2-Related Factor 2/metabolism* ; Animals ; Atherosclerosis/metabolism* ; Inflammasomes/drug effects* ; Male ; Sirtuin 1/metabolism* ; Signal Transduction/drug effects* ; Humans ; Endothelial Cells/pathology* ; Mice ; Oxidative Stress/drug effects* ; Apoptosis/drug effects* ; Lipoproteins, LDL ; Mice, Inbred C57BL

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female ; Humans ; Ovarian Neoplasms/physiopathology* ; Phosphofructokinase-2/genetics* ; Apoptosis/drug effects* ; Glycolysis/drug effects* ; Animals ; Cell Line, Tumor ; Mice ; Cell Proliferation/drug effects* ; Emodin/administration & dosage* ; Mice, Nude ; Mice, Inbred BALB C ; Hexokinase/metabolism* ; Xenograft Model Antitumor Assays

AIM To investigate the effects of Moluodan Dami Pills on chronic atrophic gastritis(CAG)rats and their mechanism.METHODS The rat models were randomly divided into the model group,the low-dose group and high-dose Moluodan Dami Pills groups(2.43 g/kg and 4.86 g/kg),and vitamin A group(0.32 g/kg),following the 16 weeks successful induction of CAG by five-factor modeling method,in contrast to another 10 normal rats of the control group.After 8 weeks corresponding administration,the rats of each group had their general physiological status and pH value of gastric juice assessed;their pathological changes of gastric mucosa observed by naked eyes combined with HE staining;their changes of gastrin-secreting cells(G cells)and somatostatin-secreting cells(D cells)in gastric mucosa observed by immunohistochemistry;and their serum levels of pepsinogen Ⅰ/pepsinogen Ⅱ(PG Ⅰ/PG Ⅱ)ratio,TNF-α and IL-6 detected by ELISA.RESULTS Compared with the model group,the groups intervened with Moluodan Damei Pills and vitamin A displayed lower pH values of gastric juice(P＜0.05),improved pathological changes of gastric mucosa,increased G and D cells counts(P＜0.05,P＜0.01),increased ratio of serum PGⅠ/PGⅡ,and decreased levels of IL-6 and TNF-α(P＜0.05,P＜0.01).CONCLUSION Moluodan Dami Pills can effectively improve the symptoms of CAG rats through its influence on the number and secretion abilityof G and D cells,the levels of serum PG Ⅰ/PG Ⅱ ratio and inflammatory factors.

Objective:To evaluate the safety and validity of perioperative antimicrobial prophylaxis with different administration period in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods:This prospective randomized controlled clinical trial was conducted on patients who underwent TURP in the Second Affiliated Hospital of Anhui Medical University from July 2022 to December 2023. The patients were randomly assigned to the experimental group and the control group in a 1∶1 ratio using a randomized block design. Inclusion criteria: age 55-78 years old, the indication of benign prostatic hyperplasia surgery, preoperative urine routine examination showed no pyuria or bacteriuria, preoperative catheterization being not reserved, postoperative pathology confirmed BPH and informed consent obtained. Exclusion criteria: severe heart, lung, brain and other diseases which could not tolerate anesthesia and surgery, complicated with bladder stones or bladder tumors, diabetic patients with poor glycemic control, immunosuppressive agents being administered. Patients in the experimental group received a single dose of cephalosporins or fluoroquinolones 30 minutes or 2 hours before surgery, while patients in the control group received a second dose 12 hours or 24 hours after the first dose. The primary outcome was the incidence of urinary tract infectious presenting fever (body temperature ≥38.5℃) within 1 week after surgery, while the white blood cell count, C-reactive protein concentration, serum heparin-binding protein concentration, red and white blood cell count in urine, the incidence of bacteriuria, pulmonary infection, and postoperative hospital stay were defined as secondary outcomes. The safety index was the incidence of adverse reactions of antibiotics.Results:A total of 180 patients were enrolled in this study, including 90 cases in each experimental group or control group. Two groups of patients had no significant difference ( P>0.05) in age [(71.7±3.9) and (69.9±4.8) years], prostate volume [55.0 ml(39.5, 62.0) and 52.5(45.5, 68.5) ml], operation time [(58.8±17.0) min vs. (60.9±16.7) min], and postoperative indwelling catheter days [3.0(3, 4) d vs. 3.8(3, 4) d]. The incidence of fever within 1 week after surgery was 7.8%(7/90) in the experimental group and 5.6%(5/90) in the control group, respectively, and the difference was not statistically significant ( P=0.550). Our data demonstrated that the white blood cell count [(10.5±1.2)×10 9/L vs. (9.7±4.1)×10 9/L], C-reactive protein concentration [(43.0±27.9) mg/L vs. (53.1±29.9) mg/L] and heparin-binding protein concentration [(44.7±19.4) ng/ml vs. (37.8±23.5) ng/ml], urine red blood cell count [4 768.2(2 387.9, 10 496.5)/μl vs. 6 577.2(3 691.5, 7 636.8) /μl], urine white blood cell count [447.1(283.9, 637.0)/μl vs 242.8(109.7, 691.8)/μl] were mildly elevated in two groups without significant difference ( P>0.05). The incidence of postoperative pulmonary infection [3.3% (3/90)] vs. 2.2% (2/90)], bacteriuria [6.7% (6/90) vs. 8.9% (8/90)], postoperative hospital stay [4.5(4.0, 5.1) days vs. 4.5(4.0, 5.5) days] also showed no significant difference ( P>0.05). While the incidence of adverse reactions of antibiotics in the experimental group 3.3% (3/90) was significantly lower than that in the control group 11.1% (10/90) ( P=0.044). Conclusions:A single-dose antibiotic administration as a perioperative antimicrobial prophylaxis is safe and effective for patients undergoing TURP who do not have preoperative pyuria or indwelling catheter.

Objective To investigate whether Heshouwuyin can delay the aging of Leydig cells in rat testis through DNA methyltransferase 1(DNMT1).Methods Totally 40 male Wistar rats were randomly divided into 4 groups,with 10 rats in each group.Immunohistochemistry was used to detect the expression levels of DNMT1 in testis tissue of rats.Testosterone content in serum of rats in each group was detected by ELISA test.A rat Leydig cell aging model was established by free radical oxidative damage.DNMT1 was knocked down by lentivirus in Leydig cells,and the cell senescence status and the testosterone content and testosterone synthesis key enzyme 3β-hydroxysteroid dehydrogenase(3β-HSD),cytochrome P450 family member 11A1(CYP11A1)content secreted by cells were detected by β-galactosidase(β-GAL)staining,immunofluorescenct staining and ELISA.Results Compared with the young control group(YCG),the expression of P16 protein and the positive rate of β-GAL in the testis tissue of rats in the natural aging group(NAG)increased significantly,and the expression of DNMT1 and serum testosterone levels decreased(P＜0.05).However,after Heshouwuyin intervention,the expression of P16 protein and the positive rate of β-GAL in the testis of aging rats were reduced,and DNMT1 expression and the serum testosterone levels increased(P＜0.05).The same trend was observed in Leydig cells.Knockdown of DNMT1 in Leydig cells,β-GAL positivity and P16 protein expression increased significantly,and testosterone secretion and testosterone synthesis key enzymes 3β-HSD,CYP11A1 content from Leydig cells decreased significantly,compared with the normal control group(NCG)(P＜0.05).When Heshouwuyin was added,the above phenomenon was improved.Conclusion Heshouwuyin can delay the aging of rat Leydig cells through DNMT1.

Sturgeon cartilage has a wide range of applications as it is rich in biologically active substances such as chondroitin sulphate and protein. In this study, the safety evaluation of sturgeon cartilage peptide in NIH/3T3 and C2C12 cells was conducted, and the results showed that sturgeon cartilage peptide did not induce apoptosis and necrosis in NIH/3T3 and C2C12 cells compared to the blank control, which provides an in vitro experimental basis for the transdermal drug delivery of sturgeon cartilage peptide. Further evaluation of the scavenging activity of sturgeon cartilage peptides against the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals showed that sturgeon cartilage peptides have strong antioxidant activity. A stable sturgeon cartilage peptide ointment containing 7% sturgeon cartilage peptide was prepared and analysed for its transdermal absorption in mouse skin. This experiment was approved by the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences (approval number: 00007684). It was found that the 12-hour cumulative release of sturgeon cartilage peptide ointment reached 92%. In this study, we further analyzed the ability of sturgeon cartilage peptide ointment to inhibit ear swelling in mice after xylene-induced inflammation. The sturgeon cartilage peptide ointment showed significant anti-inflammatory activity compared to the matrix group and the control group. In conclusion, the present study clearly demonstrated that sturgeon cartilage peptide has good safety and antioxidant activity, and the prepared sturgeon cartilage peptide ointment provides an experimental basis for further application of sturgeon cartilage peptide as well as the study of transdermal drug delivery.

Objective:To evaluate the safety and validity of perioperative antimicrobial prophylaxis with different administration period in patients undergoing transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Methods:This prospective randomized controlled clinical trial was conducted on patients who underwent TURP in the Second Affiliated Hospital of Anhui Medical University from July 2022 to December 2023. The patients were randomly assigned to the experimental group and the control group in a 1∶1 ratio using a randomized block design. Inclusion criteria: age 55-78 years old, the indication of benign prostatic hyperplasia surgery, preoperative urine routine examination showed no pyuria or bacteriuria, preoperative catheterization being not reserved, postoperative pathology confirmed BPH and informed consent obtained. Exclusion criteria: severe heart, lung, brain and other diseases which could not tolerate anesthesia and surgery, complicated with bladder stones or bladder tumors, diabetic patients with poor glycemic control, immunosuppressive agents being administered. Patients in the experimental group received a single dose of cephalosporins or fluoroquinolones 30 minutes or 2 hours before surgery, while patients in the control group received a second dose 12 hours or 24 hours after the first dose. The primary outcome was the incidence of urinary tract infectious presenting fever (body temperature ≥38.5℃) within 1 week after surgery, while the white blood cell count, C-reactive protein concentration, serum heparin-binding protein concentration, red and white blood cell count in urine, the incidence of bacteriuria, pulmonary infection, and postoperative hospital stay were defined as secondary outcomes. The safety index was the incidence of adverse reactions of antibiotics.Results:A total of 180 patients were enrolled in this study, including 90 cases in each experimental group or control group. Two groups of patients had no significant difference ( P>0.05) in age [(71.7±3.9) and (69.9±4.8) years], prostate volume [55.0 ml(39.5, 62.0) and 52.5(45.5, 68.5) ml], operation time [(58.8±17.0) min vs. (60.9±16.7) min], and postoperative indwelling catheter days [3.0(3, 4) d vs. 3.8(3, 4) d]. The incidence of fever within 1 week after surgery was 7.8%(7/90) in the experimental group and 5.6%(5/90) in the control group, respectively, and the difference was not statistically significant ( P=0.550). Our data demonstrated that the white blood cell count [(10.5±1.2)×10 9/L vs. (9.7±4.1)×10 9/L], C-reactive protein concentration [(43.0±27.9) mg/L vs. (53.1±29.9) mg/L] and heparin-binding protein concentration [(44.7±19.4) ng/ml vs. (37.8±23.5) ng/ml], urine red blood cell count [4 768.2(2 387.9, 10 496.5)/μl vs. 6 577.2(3 691.5, 7 636.8) /μl], urine white blood cell count [447.1(283.9, 637.0)/μl vs 242.8(109.7, 691.8)/μl] were mildly elevated in two groups without significant difference ( P>0.05). The incidence of postoperative pulmonary infection [3.3% (3/90)] vs. 2.2% (2/90)], bacteriuria [6.7% (6/90) vs. 8.9% (8/90)], postoperative hospital stay [4.5(4.0, 5.1) days vs. 4.5(4.0, 5.5) days] also showed no significant difference ( P>0.05). While the incidence of adverse reactions of antibiotics in the experimental group 3.3% (3/90) was significantly lower than that in the control group 11.1% (10/90) ( P=0.044). Conclusions:A single-dose antibiotic administration as a perioperative antimicrobial prophylaxis is safe and effective for patients undergoing TURP who do not have preoperative pyuria or indwelling catheter.

Objective To summarize and analyze the epidemiological and clinical characteristics of COVID-19 Omicron variant cases in makeshift hospital, and the influence of age, sex and vaccination status on the disease duration, so as to provide reference for the prevention and control of the COVID-19 epidemic. Methods The epidemiological and clinical characteristics of COVID-19 cases admitted to makeshift hospital of National Convention and Exhibition Center (Shanghai) from April 9 to May 31, 2022 were retrospectively described and analyzed, and further cohort analysis was conducted to determine the influence of age, sex and vaccination status on the disease duration of COVID-19 cases in the author's branch hospital. Results Among the 174 466 COVID-19 cases in makeshift hospital, most of them were male, accounting for 59.38%. The infected cases were mainly young and middle-aged people aged 18-59 years old, accounting for 83.50%, followed by 12.30% of the elderly group over 60 years old; the average hospital stay was 7.40 days; the proportion of patients with fever was less than 27.79%; 15.37% (26 817/174 466) of the patients complicated with underlying diseases, and the top three were hypertension, diabetes and coronary heart disease. The proportion of people who received COVID-19 vaccine accounted for 79.56% (13 799/17 956), of which the highest proportion of three doses was 44.09%. The disease duration of 17 956 COVID-19 cases in the author's branch of makeshift hospital was 10.18 (7.34, 13.05) days. The disease duration in the elderly group was the longest with 11.34 (8.35, 14.37) days, followed by 11.17 (9.07, 14.33) days in the preschool group, 10.37 (8.14, 13.34)· days in the middle-aged group, 10.07 (7.37, 12.37) days in the school-age group, and 9.34 (7.05, 12.16) days in the young group. There was significant difference in the overall distribution of disease duration among the five groups (H=550.479 P<0.01). The disease duration in each age group basically showed a V-shaped distribution. The disease duration was 10.27 (7.34, 12.57) days in males and 10.10 (7.25, 13.09) days in females, and there was no significant difference (Z=-1.505 P>0.05). The disease duration of vaccinated patients was 10.24 (7.35, 13.05) days, and that of unvaccinated patients was 9.47 (7.09, 12.47) days. There was significant difference between the two groups (Z=-4.338 P<0.01). Conclusions COVID-19 Omicron variant cases have a high proportion of males, mainly young and middle-aged, and the proportion of fever patients is less than 30%. The disease duration is significantly lower than that of the original strain in Wuhan, and shows "V" distribution with each age group. Sex had no effect on the disease duration. COVID-19 vaccination did not have a clinical effect on the disease duration.