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1.
World J Orthop ; 15(6): 593-601, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38947265

ABSTRACT

BACKGROUND: Mazabraud's syndrome (MS) is a rare and slowly progressive benign disease characterized by the concurrent presence of fibrous dysplasia of bone and intramuscular myxoma, and is thought to be associated with mutations of the GNAS gene. To date, only about 100 cases of MS have been reported in the literature, but its standard treatment strategy remains unclear. CASE SUMMARY: We report two cases of MS in young women who underwent different treatments based on their symptoms and disease manifestations. The first patient, aged 37, received internal fixation and intravenous bisphosphonate for a pathological fracture of the right femoral neck, excision of a right vastus medialis myxoma was subsequently performed for pain control, and asymptomatic psoas myxomas were monitored without surgery. Genetic testing confirmed a GNAS gene mutation in this patient. The second patient, aged 24, underwent right vastus intermedius muscle myxoma resection, and conservative treatment for fibrous dysplasia of the ilium. These patients were followed-up for 17 months and 3 years, respectively, and are now in a stable condition. CONCLUSION: Various treatments have been selected for MS patients who suffer different symptoms. The main treatment for myxomas is surgical resection, while fibrous dysplasia is selectively treated if the patient experiences pathological fracture or severe pain. However, given the documented instances of malignant transformation of fibrous dysplasia in individuals with MS, close follow-up is necessary.

2.
BMC Public Health ; 24(1): 1471, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38824589

ABSTRACT

BACKGROUND: Adolescent malignant-bone tumor patients' fear of cancer recurrence is a significant psychological issue, and exploring the influencing factors associated with fear of cancer recurrence in this population is important for developing effective interventions. This study is to investigate the current status and factors influencing fear of cancer recurrence (FCR) related to malignant bone-tumors in adolescent patients, providing evidence for future targeted mental health support and interventions. DESIGN: A cross-sectional survey. METHODS: In total, 269 adolescent malignant-bone tumor cases were treated at two hospitals in Zhejiang Province, China from January 2023 to December 2023. Patients completed a General Information Questionnaire, Fear of Progression Questionnaire-Short Form (FoP-Q-SF), Family Hardiness Index (FHI), and a Simple Coping Style Questionnaire (SCSQ). Univariate and multivariable logistic regressions analysis were used to assess fear of cancer recurrence. RESULTS: A total of 122 (45.4%) patients experienced FCR (FoP-Q-SF ≥ 34). Logistic regression analysis analyses showed that per capita-monthly family income, tumor stage, communication between the treating physician and the patient, patient's family relationships, family hardiness a positive coping score, and a negative coping score were the main factors influencing FCR in these patients (P < 0.05). CONCLUSIONS: FCR in malignant-bone tumor adolescent patients is profound. Healthcare professionals should develop targeted interventional strategies based on the identified factors, which affect these patients; helping patients increase family hardiness, helping patients to positively adapt, and avoid negative coping styles.


Subject(s)
Adaptation, Psychological , Bone Neoplasms , Fear , Neoplasm Recurrence, Local , Humans , Cross-Sectional Studies , Adolescent , Male , Female , Fear/psychology , Neoplasm Recurrence, Local/psychology , Bone Neoplasms/psychology , China , Surveys and Questionnaires , Child
3.
Front Endocrinol (Lausanne) ; 15: 1344795, 2024.
Article in English | MEDLINE | ID: mdl-38899008

ABSTRACT

Objective: While bone metastases (BMs) are present in a minority of thyroid cancer (TC) patients at the time of initial diagnosis, there has been growing concern regarding their impact on life expectancy and quality of life. The aim of this study was to identify prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in these patients and provide therapeutic recommendations based on the findings. Methods: In this retrospective cohort study, we included 82 patients diagnosed as TC with BM received treatment in our department from 2011.03 to 2023.03 (average follow-up duration was 3.02 years). The retrospective study was performed according to the inclusion and exclusion criteria. Kaplan-Meier analysis was used to estimate the OS and CSS, while the univariate and multivariate Cox proportional hazard models were employed to determine prognostic factors associated with OS and CSS. Also, 287 patients' data were collected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 to confirm the prognostic factors identified in the retrospective study. Results: The average survival time of the 82 patients was estimated to be 5.818 years (with a 95% confidence interval (CI) of 4.767 to 6.868 years). The cox regression analysis showed that older age (hazard ratio (HR) = 1.045, 95% CI: 1.001-1.092, P = 0.047), larger tumor size (>5cm, HR = 11.087, 95% CI: 3.728 - 32.976, P = 0.000), and the presence of extraosseous metastasis (HR = 3.247, 95% CI: 1.376 - 7.665, P = 0.007) were statistically significant factors associated with worse CSS. The results were furtherly confirmed in 287 SEER-sourced patients (age (HR = 1.020, 95% CI: 1.006 - 1.034, P = 0.006), tumor size (HR = 2.917, 95% CI: 2.044 - 4.161, P = 0.000), and extraosseous metastasis (HR = 3.726, 95% CI: 2.571 - 5.398, P = 0.000)). Conclusions: These results offer a population-based assessment of prognostic factors for patients with TC and BMs, revealing that age, primary tumor size (>5cm), and presence of extraosseous metastases are independent prognostic factors that correlate with worse survival. Accordingly, treatment for such patients ought to concentrate on systemic integrative therapy instead of surgical intervention.


Subject(s)
Bone Neoplasms , Thyroid Neoplasms , Humans , Thyroid Neoplasms/pathology , Thyroid Neoplasms/mortality , Thyroid Neoplasms/therapy , Male , Bone Neoplasms/secondary , Bone Neoplasms/mortality , Female , Retrospective Studies , Prognosis , Middle Aged , Adult , Aged , Survival Rate , Follow-Up Studies , Kaplan-Meier Estimate , SEER Program , Young Adult
4.
Eur J Med Chem ; 271: 116395, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38626523

ABSTRACT

The transforming growth factor ß1 (TGFß1)/SMAD signaling pathway regulates many vital physiological processes. The development of potent inhibitors targeting activin receptor-like kinase 5 (ALK5) would provide potential treatment reagents for various diseases. A significant number of ALK5 inhibitors have been discovered, and they are currently undergoing clinical evaluation at various stages. However, the clinical demands were far from being met. In this study, we utilized an alternative conformation-similarity-based virtual screening (CSVS) combined with a fragment-based drug designing (FBDD) strategy to efficiently discover a potent and active hit with a novel chemical scaffold. After structural optimization in the principle of group replacement, compound 57 was identified as the most promising ALK5 inhibitor. Compound 57 demonstrated significant inhibitory effects against the TGF-ß1/SMAD signaling pathway. It could markedly attenuate the production of extracellular matrix (ECM) and deposition of collagen. Also, the lead compound showed adequate pharmacokinetic (PK) properties and good in vivo tolerance. Moreover, treatment with compound 57 in two different xerograph models showed significant inhibitory effects on the growth of pancreatic cancer cells. These results suggested that lead compound 57 refers as a promising ALK5 inhibitor both in vitro and in vivo, which merits further validation.


Subject(s)
Drug Design , Protein Kinase Inhibitors , Pyrazoles , Pyrimidines , Receptor, Transforming Growth Factor-beta Type I , Receptor, Transforming Growth Factor-beta Type I/antagonists & inhibitors , Receptor, Transforming Growth Factor-beta Type I/metabolism , Humans , Pyrazoles/pharmacology , Pyrazoles/chemistry , Pyrazoles/chemical synthesis , Pyrimidines/pharmacology , Pyrimidines/chemistry , Pyrimidines/chemical synthesis , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Animals , Molecular Structure , Transforming Growth Factor beta1/metabolism , Transforming Growth Factor beta1/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Mice , Cell Line, Tumor , Drug Screening Assays, Antitumor , Receptors, Transforming Growth Factor beta/antagonists & inhibitors , Receptors, Transforming Growth Factor beta/metabolism
5.
Materials (Basel) ; 17(5)2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38473619

ABSTRACT

This paper studies the plastic behavior of the ZK61M magnesium alloy through a combination method of experiments and theoretical models. Based on a dog-bone specimen under different loading directions, mechanical tests under uniaxial tension were carried out, and the hardening behavior was characterized by the Swift-Voce hardening law. The von Mises yield function and the pressure-coupled Drucker yield function were used to predict the load-displacement curves of the ZK61M magnesium alloy under various conditions, respectively, where the material parameters were calibrated by using inverse engineering. The experimental results show that the hardening behavior of the ZK61M magnesium alloy has obvious anisotropy, but the effect of the stress state is more important on the strain hardening behavior of the alloy. Compared with the von Mises yield function, the pressure-coupled Drucker yield function is more accurate when characterizing the plastic behavior and strain hardening in different stress states of shear, uniaxial tension, and plane strain tension for the ZK61M alloy.

6.
Angew Chem Int Ed Engl ; 63(17): e202318568, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38433368

ABSTRACT

ATR has emerged as a promising target for anti-cancer drug development. Several potent ATR inhibitors are currently undergoing various stages of clinical trials, but none have yet received FDA approval due to unclear regulatory mechanisms. In this study, we discovered a potent and selective ATR degrader. Its kinase-independent regulatory functions in acute myeloid leukemia (AML) cells were elucidated using this proteolysis-targeting chimera (PROTAC) molecule as a probe. The ATR degrader, 8 i, exhibited significantly different cellular phenotypes compared to the ATR kinase inhibitor 1. Mechanistic studies revealed that ATR deletion led to breakdown in the nuclear envelope, causing genome instability and extensive DNA damage. This would increase the expression of p53 and triggered immediately p53-mediated apoptosis signaling pathway, which was earlier and more effective than ATR kinase inhibition. Based on these findings, the in vivo anti-proliferative effects of ATR degrader 8 i were assessed using xenograft models. The degrader significantly inhibited the growth of AML cells in vivo, unlike the ATR inhibitor. These results suggest that the marked anti-AML activity is regulated by the kinase-independent functions of the ATR protein. Consequently, developing potent and selective ATR degraders could be a promising strategy for treating AML.


Subject(s)
Antineoplastic Agents , Leukemia, Myeloid, Acute , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/therapeutic use , Cell Line, Tumor , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/metabolism , Proteolysis , Tumor Suppressor Protein p53/metabolism
8.
Bioorg Med Chem ; 91: 117404, 2023 08 15.
Article in English | MEDLINE | ID: mdl-37429211

ABSTRACT

A series of novel substituted 4-anilinoquinazolines and their related compounds were designed and prepared by 3D modeling as potential inhibitors of VEGFR-2. Evaluation of VEGFR inhibitory activities suggested that compound I10 was a more potent (IC50 = 0.11 nM) VEGFR-2 inhibitor than most of the listed drugs. Kinase panel assays demonstrated that compound I10 was the selective VEGFR-2 inhibitor. The prediction of 3D modeling unveiled a unique binding mode of this lead compound to VEGFR-2. Compound I10 exhibited remarkable anti-angiogenesis and anti-proliferation in HUVEC at low nanomolar concentrations. PK studies indicated that the lead compound possessed adequate oral bioavailability in various species. In vivo subcutaneous tumor model demonstrated that oral administration of I10 demonstrated potent efficacy in inhibiting tumor growth and angiogenesis. All these results suggested compound I10 is a potential drug candidate for cancer treatment.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Vascular Endothelial Growth Factor Receptor-2 , Neoplasms/drug therapy , Phosphorylation , Protein Kinase Inhibitors/chemistry , Cell Proliferation , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Drug Screening Assays, Antitumor , Molecular Docking Simulation , Molecular Structure
9.
Iran J Basic Med Sci ; 26(4): 468-477, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37009012

ABSTRACT

Objectives: Cervical cancer (CC) is the fourth most prevalent type of cancer in women worldwide and it is considered the leading cause of tumor-related death and malignancy. As part of complexes involved in epigenetic control, the proteins of the chromobox (CBX) family have been found to have a role in the growth of malignancies by preventing differentiation and increasing proliferation. Here, by a thorough investigation, we investigated the expression, prognostic significance, and immune infiltration of CBX in patients with CC. Materials and Methods: Differential expression, clinicopathological parameters, immune cell infiltration, enrichment analysis, genetic alteration, and prognostic value of CBXs in patients with CC were examined using TIMER, Metascape, STRING, GeneMANIA, cBioPortal, UALCAN, The Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine. Results: In CC tissues, CBX 2/3/4/5 and CBX 8 expression levels were considerably higher, whereas CBX 6/7 expression levels were lower. In CC, the CBX 5/6/8 promoters have elevated levels of methylation. The expression of CBX 2/6/8 and the pathological stage were connected. A 37% mutation rate of the differentially expressed CBX genes was observed. Also, there was a strong correlation of the CBXs expression with immune cell infiltration, such as T CD4+ cells, macrophages, neutrophils, B cells, T CD8+ cells, and dendritic cells. Conclusion: The investigation discovered that members of the CBXs family may be therapeutic targets for CC patients and may play significant roles in the development of CC tumors.

10.
Appl Bionics Biomech ; 2022: 2021162, 2022.
Article in English | MEDLINE | ID: mdl-36267672

ABSTRACT

Clinical trials on pediatric oncology use therapeutic techniques with the overwhelming majority of children's cancer patients obtaining therapy via clinical investigation procedures. Medical treatment is scheduled according to a specific protocol for enrolled patients. These protocols often do not refer to nursing care. Nursing care, on the other hand, must complement the medical care specified in the medical research protocol. Safe treatment administration, assessment of treatment responses, patients' and families' education, and communication with the whole medical team are just a few of the critical nursing tasks that should be properly managed. Nursing care standards have been developed in this study to strike a good balance between the procedure for clinical research and the nursing care connected with it. These recommendations outline the nursing activities and considerations that must be made while caring for pediatric cancer patients who are engaged in a specific clinical investigation procedure. The objective of this study is to outline the procedure through which nursing care guidelines could be developed and evaluated. The goal of this study was to find out the involvement of nurses in the process of health education for osteosarcoma and family patients.

11.
Med Sci Monit ; 28: e937496, 2022 Sep 13.
Article in English | MEDLINE | ID: mdl-36097401

ABSTRACT

BACKGROUND The present study aimed to investigate the effects of implementing the Registered Nurses' Association of Ontario (RNAO) guidelines for the management of postoperative pain and the use of Jacobson's relaxation technique (JRT) in patients with bone and soft-tissue malignancy at a single center in China. MATERIAL AND METHODS A total of 312 patients were recruited and randomly divided into 2 groups. In the intervention group, the RNAO pain-management technique of JRT was adopted, while the control group received the standard institutional nursing management. Pain scores after the operation, according to the Numerical Rating Scale (NRS) combined with the Wong-Baker Faces Pain Rating Scale and Short-Form McGill Pain Questionnaire, were compared between the 2 groups. Nursing satisfaction was compared as well. RESULTS At 6, 24, and 72 h after the operation, the NRS scores combined with the Wong-Baker Faces Pain Rating Scale in the intervention group were significantly lower than those in the control group (P<0.001); 72 h after the operation, the Pain Rating Index, Visual Analogue Scale, present pain intensity, and total scores for the intervention group were significantly lower than those for the control group (P<0.001 for all 4 scores). The scores reported from the patients for nursing response and consequent care (P<0.001), nursing competence (P=0.029), and surgical pain-control satisfaction (P<0.001) in the intervention group were also significantly higher than those in the control group. CONCLUSIONS JRT can improve postoperative pain-control and nursing satisfaction in patients with malignant bone and soft-tissue tumors. These data suggest a benefit for application of JRT in clinical care.


Subject(s)
Nurses , Sarcoma , Case-Control Studies , Humans , Ontario , Pain, Postoperative , Relaxation Therapy
12.
PLoS One ; 17(8): e0266519, 2022.
Article in English | MEDLINE | ID: mdl-35994492

ABSTRACT

The friction coefficient between the tire and the road is one of the key parameters affecting road traffic safety. The purpose of this paper is to quantify the risk of skidding for the vehicles due to the friction evolution caused by the traffic polishing in the horizontal curve. Based on the reliability theory, an innovative dynamic risk assessment model is developed in the present study for passenger cars and trucks. The influence of two traffic characteristics for pavement friction is quantified: cumulative traffic volume (CTV) and annual average daily traffic of trucks (AADTT). The speed distribution on the horizontal curve of the motorway is obtained through field experiments as the basic parameter of the model. The Hasofer-Lind Method is adopted to solve the reliability and the risk probability of vehicle skidding. The results show that in the traffic characteristics, the AADTT has a significant impact on the pavement friction; When the AADTT on the road exceeds 2000 veh/d, the increasing CTV leads to friction decrease rapidly and therefore has a significant impact on the risk of horizontal curve. Especially for roads with more than 50 million vehicles of the CTV, the risk of the horizontal curve shows a sharp increase with CTV rising. The research results can provide reference for the road maintenance department to determine the timing of road maintenance.


Subject(s)
Automobile Driving , Accidents, Traffic , Friction , Reproducibility of Results , Safety
13.
Ann Transl Med ; 9(20): 1517, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34790723

ABSTRACT

BACKGROUND: It has been demonstrated that berberine (BBR), a kind of alkaloid derived from Chinese herbal medicine, has multiple pharmacological effects on human's diseases including anti-atherosclerosis action. However, although the previous studies showed that the beneficial impact of BBR on atherosclerosis might be associated with proprotein convertase subtilisin/kexin type 9 (PCSK9), the exact underlying mechanism are not fully determined. The present study aimed to investigate potential mechanisms of anti-atherosclerosis by BBR using ApoE-/- mice. METHODS: The eight-week mice were divided into five groups: group 1 (wild type C57BL/6J mice with normal diet), group 2 (ApoE-/- mice with normal diet), group 3 [ApoE-/- mice with high-fat diet (HFD)], group 4 (ApoE-/- mice with HFD, and treatment with low dose BBR of 50 mg/kg/d), and group 5 (ApoE-/- mice with HFD, and treatment with high dose BBR of 100 mg/kg/d). After a 16-week treatment, the blood sample, aorta and liver were collected for lipid analysis, hematoxylin-eosin (HE) or oil red O staining, and Western blotting respectively. Besides, HepG2 Cells were cultured and treated with different concentrations of BBR (0, 5, 25 and 50 µg/mL) for 24 hours. Subsequently, cells were collected for real-time PCR or western blotting assays. Finally, the expression levels of PCSK9, LDL receptor (LDLR), ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor class B type I (SR-BI) were examined. RESULTS: Fifty mg/kg/d and 100 mg/kg/d of BBR decreased total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol (LDL-C), and increased high-density lipoprotein cholesterol (HDL-C) level. Moreover, BBR reduced aorta atherosclerotic plaque, and ameliorated lipid deposition in ApoE-/- mice fed with HFD. Finally, in vitro study showed that BBR promoted intracellular cholesterol efflux, up-regulated LDLR and down-regulated PCSK9 expression via the ERK1/2 pathway in cultured HepG2 cells. CONCLUSIONS: Data indicated that BBR significantly attenuated lipid disorder, reduced aortic plaque formation, and alleviated hepatic lipid accumulation in ApoE-/- mice fed with HFD, which was associated with down-regulation of PCSK9 through ERK1/2 pathway.

14.
J Med Chem ; 64(22): 16497-16511, 2021 11 25.
Article in English | MEDLINE | ID: mdl-34694800

ABSTRACT

Acute myeloid leukemia (AML) refers to one of the most lethal blood malignancies worldwide. FLT3-ITD mutation is recognized as the most common one that predicted a poorer prognosis. There have been many prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies. However, as impacted by undesirable off-target effects, differentiated metabolic issues, and clinical drug resistance problems, it remains challenging to discover alternative and promising solutions for treating FLT3-ITD+ AML. In this study, dovitinib was chemically modified and converted into CRBN-recruiting PROTACs. Two active compounds were identified, which showed enhanced antiproliferative effects against FLT3-ITD+ AML cells, both in vitro and in vivo. As demonstrated from further biological evaluation, the compounds could induce the degradation of the FLT3-ITD and KIT proteins in a ubiquitin-proteasome-dependent manner and completely block their downstream signaling pathway. The findings of this study would provide another promising strategy to develop novel therapies for FLT3-ITD+ AML.


Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Benzimidazoles/chemistry , Benzimidazoles/pharmacology , Leukemia, Myeloid, Acute/metabolism , Quinolones/chemistry , Quinolones/pharmacology , fms-Like Tyrosine Kinase 3/metabolism , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , Mutation , Proteasome Endopeptidase Complex/metabolism , Proteolysis/drug effects , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Structure-Activity Relationship , Ubiquitin/metabolism , fms-Like Tyrosine Kinase 3/genetics
15.
BMC Psychiatry ; 21(1): 253, 2021 05 17.
Article in English | MEDLINE | ID: mdl-34001048

ABSTRACT

BACKGROUND: To investigate a 3-stage screening procedure and explore the clinical features of subjects at Clinical High Risk (CHR) for psychosis in a representative sample of Chinese college students. METHODS: An epidemiological survey of the prevalence of the CHR syndrome in Chinese college students that was selected by stratified random sampling from Shanghai, Nanjing and Nanchang cities was done following a 3-stage procedure. Participants were initially screened with the Prodromal Questionnaire-brief version (PQ-B), and whose distress score of PQ-B exceeded 24 would be invited to a telephone assessment using the subscale for positive symptoms of the Scale of Prodromal Symptoms (SOPS)/Structured Interview for Prodromal Syndromes (SIPS). Lastly, participants who scored 3 or higher in any item of the subscale would be administered with the SIPS interview conducted by trained researchers to confirm the diagnosis of CHR syndrome. RESULTS: Twenty-three thousand sixty-three college students completed the survey during September 2017 to October 2018. Seventy-two students were diagnosed as CHR subjects, and the detection rate in the total sample was 0.3%. The peak age range for the first diagnosis of CHR was 17 to 20 years. Thirteen and forty-six were set as the cutoff points of PQ-B total score and distress score to balance the greatest sensitivity and specificity. Binary logistic regression revealed that 8 items in PQ-B showed significant distinction for detecting CHR subjects. CONCLUSIONS: The 3-stage screening method can be utilized in the detection of CHR subjects for psychosis in the general population, during which delusional ideas, perceptual abnormalities and suspiciousness deserve great attention.


Subject(s)
Psychotic Disorders , Adolescent , Adult , China/epidemiology , Epidemiologic Studies , Humans , Prodromal Symptoms , Psychiatric Status Rating Scales , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Students , Young Adult
16.
Bioorg Chem ; 111: 104833, 2021 06.
Article in English | MEDLINE | ID: mdl-33839580

ABSTRACT

Immunotherapy via immune checkpoints blockade has aroused the attention of researchers worldwide. Inhibition of the programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) interaction has been one of the most promising immunotherapy strategies. Several neutralizing antibodies targeting this interaction have been developed, which have already achieved considerable clinical success. Additionally, numerous pharmaceutical companies have been committed to develop small molecules which could block the interaction between PD-1 and PD-L1. In this study, a novel PROTAC molecule 21a was developed, and effectively induced the degradation of PD-L1 protein in various malignant cells in a proteasome-dependent manner. Moreover, compound 21a could significantly reduce PD-L1 protein levels of MC-38 cancer cells in vivo, by which promoted the invasion of CD8+ T cells and inhibited the growth of MC-38 in vivo. This PROTAC molecule could be used as a novel and alternative strategy for cancer immunotherapy.


Subject(s)
Amines , Antineoplastic Agents , B7-H1 Antigen , Proteolysis , Animals , Female , Mice , Amines/chemical synthesis , Amines/chemistry , Amines/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Mice, Inbred C57BL , Molecular Structure , Structure-Activity Relationship
17.
Biomed Res Int ; 2021: 8862282, 2021.
Article in English | MEDLINE | ID: mdl-33542928

ABSTRACT

PURPOSE: To evaluate the clinical efficacy of prodom in the administration of urokinase in the vagina in couples with impaired semen liquefaction. MATERIALS AND METHODS: Overall, 261 patients with impaired semen liquefaction were randomly divided into prodom-assisted urokinase treatment (PAUT) group (n = 91), syringe-assisted urokinase treatment (SAUT) group (n = 86), and traditional treatment (TT) group (n = 84) in the first stage. If the first stage of treatment failed, other treatment methods were initiated instead and the patients were grouped according to the newer treatment method in the second stage. The pregnancy rate, time-to-conception, and treatment costs were evaluated in each group. RESULTS: In the first stage, the pregnancy rate in the PAUT, SAUT, and TT groups was 69.23%, 29.07%, and 22.62%, respectively; the time-to-conception was 2.66 ± 1.44, 3.69 ± 2.61, and 3.86 ± 3.00 months, respectively; the treatment costs were 658.18 ± 398.40, 666.67 ± 507.50, and 680.56 ± 480.94 $, respectively. The pregnancy rate and time-to-conception were different in the PAUT group compared with those in SAUT and TT groups (all P < 0.05). However, the difference in treatment costs was not significant (P = 0.717). In the second stage, 154 nonpregnant patients were divided into nine treatment groups, and the effects of changing TT to PAUT on the pregnancy rate, time-to-conception, and treatment costs were observed to be different from those of other treatments (all P < 0.05). CONCLUSION: Prodom-assisted urokinase can effectively treat male infertility secondary to impaired semen liquefaction.


Subject(s)
Infertility, Male/drug therapy , Semen/drug effects , Sperm Motility/physiology , Urokinase-Type Plasminogen Activator/administration & dosage , Adult , Female , Humans , Infertility, Male/metabolism , Infertility, Male/pathology , Male , Middle Aged , Pregnancy , Pregnancy Rate , Semen/chemistry , Semen/physiology , Sperm Count , Vagina/physiology , Young Adult
18.
Int J Oncol ; 56(6): 1417-1428, 2020 06.
Article in English | MEDLINE | ID: mdl-32236589

ABSTRACT

Osteosarcoma is the most common primary malignant tumor of the bone and the long­term survival of patients with this disease has remained unsatisfactory over the past several decades. Andrographolide, a traditional drug used in Chinese medicine, has been found to exert a significant antitumor effect against several types of cancer. However, relatively little is known about the effect of andrographolide on osteosarcoma and the underlying mechanisms. In the present study, it was shown that andrographolide inhibited osteosarcoma cell proliferation by arresting the cell cycle at the G2/M phase and increasing caspase­mediated apoptosis. Furthermore, treatment with andrographolide induced JNK activation and increased production of reactive oxygen species (ROS). The andrographolide­triggered apoptosis in osteosarcoma cells was partly abrogated by a JNK inhibitor and completely reversed by a ROS scavenger. Additionally, JNK activation and cell cycle arrest at the G2/M phase were prevented by administration of an ROS scavenger. In vivo, it was also found that andrographolide inhibited tumor growth by increasing the levels of ROS and activating JNK; thus inducing cytotoxicity in primary osteosarcoma cells. Together, the results of the present study suggest that andrographolide caused G2/M arrest and induced cell apoptosis via regulation of the ROS/JNK signaling pathway in osteosarcoma cells. Thus, andrographolide may serve as a promising antitumor therapeutic agent against osteosarcoma.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Bone Neoplasms/drug therapy , Diterpenes/administration & dosage , MAP Kinase Signaling System/drug effects , Osteosarcoma/drug therapy , Reactive Oxygen Species/metabolism , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Bone Neoplasms/metabolism , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Diterpenes/pharmacology , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Mice , Osteosarcoma/metabolism , Time Factors , Xenograft Model Antitumor Assays
19.
J Health Psychol ; 25(6): 733-737, 2020 05.
Article in English | MEDLINE | ID: mdl-32301628

ABSTRACT

Disaster psychological assistance has become an important part of the disaster relief system, playing a crucial role in restoring and maintaining emotional stability and security of people and reducing trauma-related stress. As the first country to experience the outbreak of the coronavirus disease 2019 (COVID-19), China actively adopted psychological assistance measures in response to the panic caused by the epidemic. These measures are expected to help the Chinese government and governments in other parts of the world to better respond to the outbreaks of COVID-19.


Subject(s)
Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Disease Outbreaks , Mental Health Services/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , COVID-19 , China/epidemiology , Humans , Pandemics
20.
Materials (Basel) ; 13(2)2020 Jan 12.
Article in English | MEDLINE | ID: mdl-31940880

ABSTRACT

To improve the corrosion performance of magnesium alloys in the marine environment, the MAO, MAO-Cu2CO3(OH)2·H2O and MAO-Cu2P2O7 ceramic coatings were deposited on AZ91D magnesium alloys in basic electrolyte and the discoloration mechanism of the Cu-doped MAO coatings and the corrosion behavior of the three MAO coatings in the artificial seawater solution were investigated by SEM, EDS and XPS. The results indicated that the formation and discoloration mechanism of the brown MAO ceramic coatings were attributable to the formation of Cu2O in the coatings. Though the three MAO coatings had a certain protective effect against the corrosion of AZ91D substrate in the artificial seawater, the distinctive stratification phenomenon was found on the MAO-Cu2P2O7 coated sample and the corrosion model of the MAO-Cu2P2O7 coatings in the immersion experiment was established. Therefore, the brown Cu-doped MAO coatings were speculated to significantly reduce the risk of the magnesium parts in marine environments.

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