Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 71
Filter
1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 911-919, 2024 Jun.
Article in Chinese | MEDLINE | ID: mdl-38926988

ABSTRACT

OBJECTIVE: To screen interleukin (IL)-1ß secretion-related membrane transporters by macrophage experiment in vitro and conventional knockout mice. METHODS: THP-1 cell line was differentiated to obtain human THP-1-derived macrophages, and the primary macrophages were obtained from human peripheral blood. FVB wild-type mice with the same sex and age were used as the controls of MRP1 knockout mice. The macrophages in abdominal cavity and bone marrow of mice were cultivated. The cells were treated with ABCC1/MRP1, ABCG2/BCRP, ABCB1/P-gp, OATP1B1, and MATE transporter inhibitors, then stimulated by lipopolysaccharide and adenosine triphosphate. The secretion level of IL-1ß was detected by ELISA, Western blot, and immunofluorescence. RESULTS: After inhibiting ABCC1/MRP1 transporter, the secretion of IL-1ß decreased significantly, while inhibition of the other 4 transporters had no effect. In animal experiment, the level of IL-1ß secreted by macrophages in bone marrow of MRP1 knockout mice was significantly lower than control group (P < 0.05). CONCLUSION: ABCC1/MRP1 transporter is a newly discovered IL-1ß secretion pathway, which is expected to become a new target for solving clinical problems such as cytokine release syndrome.


Subject(s)
Down-Regulation , Interleukin-1beta , Macrophages , Mice, Knockout , Multidrug Resistance-Associated Proteins , Interleukin-1beta/metabolism , Mice , Animals , Humans , Multidrug Resistance-Associated Proteins/metabolism , Macrophages/metabolism , THP-1 Cells , Lipopolysaccharides
2.
Gynecol Endocrinol ; 40(1): 2360085, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38813955

ABSTRACT

Premature ovarian insufficiency (POI) is a common gynecological endocrine disease, which seriously affects women's physical and mental health and fertility, and its incidence is increasing year by year. With the development of social economy and technology, psychological stressors such as anxiety and depression caused by social, life and environmental factors may be one of the risk factors for POI. We used PubMed to search peer-reviewed original English manuscripts published over the last 10 years to identify established and experimental studies on the relationship between various types of stress and decreased ovarian function. Oxidative stress, follicular atresia, and excessive activation of oocytes, caused by Stress-associated factors may be the main causes of ovarian function damage. This article reviews the relationship between psychological stressors and hypoovarian function and the possible early intervention measures in order to provide new ideas for future clinical treatment and intervention.


Subject(s)
Primary Ovarian Insufficiency , Stress, Psychological , Humans , Primary Ovarian Insufficiency/psychology , Primary Ovarian Insufficiency/etiology , Primary Ovarian Insufficiency/therapy , Female , Stress, Psychological/complications , Oxidative Stress/physiology , Risk Factors , Depression/etiology
3.
Crit Rev Immunol ; 44(4): 51-60, 2024.
Article in English | MEDLINE | ID: mdl-38505921

ABSTRACT

This study aimed to elucidate the role of microRNA-503 (miR-503) in pancreatic cancer (PC) progression and the underlying regulatory mechanisms. We acquired miR-503-3p and miR-503-5p expression data along with survival times of PC and normal samples from the UCSC Xena database. Using the t-test, we compared the expression of miR-503-3p and miR-503-5p between PC and normal samples, and evaluated their prognostic significance via Kaplan-Meier survival analysis. The expression of miR-503-5p in PC cells was detected by quantitative PCR. We subsequently overexpressed miR-503-5p in PC cells and examined cell viability, apoptosis, and migration through CCK8 assay, flow cytometry, and Transwell assay, respectively. Potential functional targets were identified using miRTarBase and validated by dual-luciferase reporter assay. Both miR-503-3p and miR-503-5p expression were found to be downregulated in PC; however, only miR-503-5p was linked to cancer prognosis based on public data. In vitro experiments demonstrated that overexpression of miR-503-5p substantially decreased cell viability, induced apoptosis, caused G0/G1 arrest, and inhibited cell migration. miR-503-5p was found to target cyclin E2 (CCNE2), and overexpression of CCNE2 could counteract the effects of miR-503-5p on PC cells. Conclusion: The downregulation of miR-503-5p enhances the progression of PC by targeting CCNE2. The detection of miR-503-5p expression may provide valuable insights for the prevention and prognostic evaluation of PC.


Subject(s)
MicroRNAs , Pancreatic Neoplasms , Humans , MicroRNAs/genetics , Down-Regulation , Cell Line, Tumor , Cell Proliferation/genetics , Cyclins/metabolism , Pancreatic Neoplasms/genetics , Gene Expression Regulation, Neoplastic
4.
Adv Healthc Mater ; 13(5): e2302927, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37986024

ABSTRACT

The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , SARS-CoV-2/physiology , Peptides/metabolism , Artificial Intelligence , Protein Binding
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(5): 1523-1530, 2023 Oct.
Article in Chinese | MEDLINE | ID: mdl-37846711

ABSTRACT

OBJECTIVE: To explore the effect of human bone marrow mesenchymal stem cells (MSCs) with ectopic high OCT4 expression on T-cell proliferation, activation and secretion in vitro. METHODS: Peripheral blood mononuclear cells were isolated from healthy children. Anti-CD3 and anti-CD28 monoclonal antibodies were used to activate T lymphocytes, which were stimulated by interleukin (IL)-2 for one week in vitro. Then MSCs with ectopic high OCT4 expression (MSC-OCT4) were co-cultured with activated T lymphocytes. After one week of co-culture, the supernatant was collected and the levels of Th1/Th2 cytokines [IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α and interferon (IFN)-γ] were determined by flow cytometry. The lymphocytes after one week of co-culture were collected and counted by Countstar software. After the proportions of activated/inactivated T cell subsets were determined by flow cytometry, the absolute lymphocyte counts were calculated and expressed as mean ± standard deviation. RESULTS: Compared with control T cell alone culture group, the proliferation of CD3+ T cells, CD3+CD4+ T cells, and CD3+CD8+ T cells were significantly inhibited in MSC group and MSC-OCT4 group. Compared with MSC, MSC-OCT4 could inhibit CD3+CD8+ T cell proliferation better (P =0.049), and mainly inhibited early T cell activation. Compared with control T cell alone culture group, the levels of IL-2 and INF-γ were significantly down-regulated both in MSC group and MSC-OCT4 group.After co-culture with T cells for one week, the level of IL-6 significantly increased in MSC group and MSC-OCT4 group compared with that before co-culture. Compared with control MSC group, MSC-OCT4 group had higher viable cell numbers after 1 week of co-culture (P =0.019), and could resist the inhibition of proliferation by higher concentration of mitomycin C. CONCLUSION: Both MSC and MSC-OCT4 can inhibit the proliferation and activation of IL-2-stimulated T cells in vitro. After overexpression of OCT4, MSC has better proliferation ability in vitro and can inhibit the proliferation of CD3+CD8+ T cells more effectively, which may have a better and more lasting immunosuppressive ability to regulate the balance of Th1/Th2.


Subject(s)
Interleukin-2 , Mesenchymal Stem Cells , Child , Humans , Bone Marrow Cells , CD8-Positive T-Lymphocytes/metabolism , Cell Proliferation , Cells, Cultured , Interleukin-6/metabolism , Leukocytes, Mononuclear/metabolism , Lymphocyte Activation , Tumor Necrosis Factor-alpha/metabolism
6.
ACS Nano ; 17(11): 10407-10422, 2023 06 13.
Article in English | MEDLINE | ID: mdl-37120837

ABSTRACT

Since glioblastomas (GBMs) are radioresistant malignancies and most GBM recurrences occur in radiotherapy, increasing the effectiveness of radiotherapy by gene-silencing has recently attracted attention. However, the difficulty in precisely tuning the composition and RNA loading in nanoparticles leads to batch-to-batch variations of the RNA therapeutics, thus significantly restricting their clinical translation. Here, we bioengineer bacteriophage Qß particles with a designed broccoli light-up three-way junction (b-3WJ) RNA scaffold (contains two siRNA/miRNA sequences and one light-up aptamer) packaging for the silencing of genes in radioresistant GBM cells. The in vitro results demonstrate that the cleavage of de novo designed b-3WJ RNA by Dicer enzyme can be easily monitored in real-time using fluorescence microscopy, and the TrQß@b-3WJLet-7gsiEGFR successfully knocks down EGFR and IKKα simultaneously and thereby inactivates NF-κB signaling to inhibit DNA repair. Delivery of TrQß@b-3WJLet-7gsiEGFR through convection-enhanced delivery (CED) infusion followed by 2Gy X-ray irradiation demonstrated that the median survival was prolonged to over 60 days compared with the 2Gy X-ray irradiated group (median survival: 31 days). Altogether, the results of this study could be critical for the design of RNAi-based genetic therapeutics, and CED infusion serves as a powerful delivery system for promoting radiotherapy against GBMs without evidence of systemic toxicity.


Subject(s)
Bacteriophages , Glioblastoma , MicroRNAs , Nanoparticles , Humans , Glioblastoma/genetics , Glioblastoma/therapy , Glioblastoma/pathology , RNAi Therapeutics/methods , Cell Line, Tumor , MicroRNAs/genetics , RNA, Small Interfering/genetics , RNA Interference
7.
JMIR Form Res ; 7: e40207, 2023 Feb 27.
Article in English | MEDLINE | ID: mdl-36848207

ABSTRACT

BACKGROUND: Mobile instant messaging (IM) apps (eg, WhatsApp and WeChat) have been widely used by the general population and are more interactive than text-based programs (SMS text messaging) to modify unhealthy lifestyles. Little is known about IM app use for health promotion, including alcohol reduction for university students. OBJECTIVE: This study aims to explore university student drinkers' perceptions of using IM apps for alcohol reduction as they had high alcohol exposure (eg, drinking invitations from peers and alcohol promotion on campus) and the proportion of IM app use in Hong Kong. METHODS: A qualitative study was conducted with 20 Hong Kong Chinese university students (current drinkers) with Alcohol Use Disorder Identification test scores of ≥8 recruited using purposive sampling. Semistructured individual interviews were conducted from September to October 2019. Interview questions focused on drinking behaviors, quitting history, opinions toward IM app use as an intervention tool, perceived usefulness of IM apps for alcohol reduction, and opinions on the content and design of IM apps for alcohol reduction. Each interview lasted approximately 1 hour. All interviews were audio-taped and transcribed verbatim. Two researchers independently analyzed the transcripts using thematic analysis with an additional investigator to verify the consistency of the coding. RESULTS: Participants considered IM apps a feasible and acceptable platform for alcohol reduction intervention. They preferred to receive IMs based on personalized problem-solving and drinking consequences with credible sources. Other perceived important components of instant messages included providing psychosocial support in time and setting goals with participants to reduce drinking. They further provided suggestions on the designs of IM interventions, in which they preferred simple and concise messages, chat styles based on participants' preferences (eg, adding personalized emojis and stickers in the chat), and peers as counselors. CONCLUSIONS: Qualitative interviews with Chinese university student drinkers showed high acceptability, engagement, and perceived utility of IM apps for alcohol reduction intervention. IM intervention can be an alternative for alcohol reduction intervention apart from traditional text-based programs. The study has implications for developing the IM intervention for other unhealthy behaviors and highlights important topics that warrant future research, including substance use and physical inactivity. TRIAL REGISTRATION: ClinicalTrials.gov NCT04025151; https://clinicaltrials.gov/ct2/show/NCT04025151?term=NCT04025151.

8.
Carbohydr Polym ; 305: 120535, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36737188

ABSTRACT

In this paper, we proposed a novel and green strategy based on water evaporation induced in-situ interfacial compatibilization (WEIC) mechanism for fabricating high-strength and all-natural lignocellulose/starch composites. This mechanism exploits the natural compatibility of the lignocellulose and starch and was tested through an internal mixing process with regulated water evaporation. Specifically, we revealed that a restrained layer was in-situ formed at the interface of the lignocellulose and starch during the internal mixing process; a faster water evaporation rate thickens this restrained layer, restricts the starch's molecular movement and significantly increases the composite's mechanical properties. The highest tensile strength and Young's modulus of the composites achieved are 21.7 ± 0.8 MPa and 2.2 ± 0.1 GPa, respectively, superior to many existing starch/lignocellulose composites. Thus, this work provides new insight into the compatibilization of various hydrophilic polysaccharides and paves new avenues for developing greener and more facile methods to fabricate all-polysaccharide composites.

9.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1008114

ABSTRACT

Uric acid (UA) is the final product of purine metabolism in human body,and its metabolic disorder will induce hyperuricemia (HUA).The occurrence and development of HUA are associated with a variety of pathological mechanisms such as oxidative stress injury,activation of inflammatory cytokines,and activation of renin-angiotensin-aldosterone system.These mechanisms directly or indirectly affect the bioavailability of endogenous nitric oxide (NO).The decrease in NO bioavailability is common in the diseases with high concentration of UA as an independent risk factor.In this review,we summarize the mechanisms by which high concentrations of UA affect the endogenous NO bioavailability,with a focus on the mechanisms of high-concentration UA in decreasing the synthesis and/or increasing the consumption of NO.This review aims to provide references for alleviating the multisystem symptoms and improving the prognosis of HUA,and lay a theoretical foundation for in-depth study of the correlations between HUA and other metabolic diseases.


Subject(s)
Humans , Nitric Oxide , Uric Acid , Hyperuricemia , Biological Availability , Cytokines
10.
International Eye Science ; (12): 933-937, 2023.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-973780

ABSTRACT

Glaucoma, currently the world's first irreversible blindness, is a complex multifactorial disease with a genetic predisposition, and pathologically elevated intraocular pressure is its risk factor. The pathogenesis of glaucoma is not fully understood, and most existing studies are based on animal models, with mice as the main research object, and the pathological damage process of glaucoma is reconstructed through experimental induction means or transgenic manipulation to further investigate the relevant pathogenesis and pathological changes. The technique of experimentally induced construction of glaucoma mouse models has been studied by many scholars and is gradually becoming mature. And as research in molecular biology and genetics has advanced, more and more studies have focused on the disease genes associated with glaucoma, and transgenic mouse models have become a hot topic in recent years. In contrast to experimental manipulation to control a single factor, gene editing is better able to simulate the complex process of disease pathogenesis. This paper focuses on providing a more complete direction and strategy for model selection in the future research by describing the progress of research on relevant transgenic mouse model of glaucoma.

11.
World J Stem Cells ; 14(11): 777-797, 2022 Nov 26.
Article in English | MEDLINE | ID: mdl-36483848

ABSTRACT

Corneal stem/progenitor cells are typical adult stem/progenitor cells. The human cornea covers the front of the eyeball, which protects the eye from the outside environment while allowing vision. The location and function demand the cornea to maintain its transparency and to continuously renew its epithelial surface by replacing injured or aged cells through a rapid turnover process in which corneal stem/progenitor cells play an important role. Corneal stem/progenitor cells include mainly corneal epithelial stem cells, corneal endothelial cell progenitors and corneal stromal stem cells. Since the discovery of corneal epithelial stem cells (also known as limbal stem cells) in 1971, an increasing number of markers for corneal stem/progenitor cells have been proposed, but there is no consensus regarding the definitive markers for them. Therefore, the identification, isolation and cultivation of these cells remain challenging without a unified approach. In this review, we systematically introduce the profile of biological characterizations, such as anatomy, characteristics, isolation, cultivation and molecular markers, and clinical applications of the three categories of corneal stem/progenitor cells.

12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(6): 1902-1906, 2022 Dec.
Article in Chinese | MEDLINE | ID: mdl-36476923

ABSTRACT

Although chimeric antigen receptor (CAR)-T therapy has produced remarkable clinical responses for patients with relapsed or refractory hematological malignancies, setbacks were experienced, including antigen escape and heterogeneity, its efficacy and safety issues. In recent years, researchers at home and abroad are addressing the current obstacles by digging deeply into structural optimization of CAR gene in order to solve the problems of CAR-T cell therapy. In this review, we mainly illustrate the ectodomain structure, transmemberane domain, and endodomain structure, and new designs which promote persistence of CAR-T cells in vivo, so as to provide new ideas for improving the safety and the efficacy of CAR-T cell therapy.


Subject(s)
Receptors, Chimeric Antigen , Humans , T-Lymphocytes
13.
Stem Cell Investig ; 9: 4, 2022.
Article in English | MEDLINE | ID: mdl-36238449

ABSTRACT

Background and Objective: Stem cell therapy (SCT) is one of the vastly researched branches of regenerative medicine as a therapeutic tool to treat incurable diseases. With the use of human stem cells such as embryonic stem cells (ESCs), adult stem cells (ASCs) and induced pluripotent stem cells (iPSCs), stem cell therapy aims to regenerate or repair damaged tissues and congenital defects. As stem cells are able to undergo infinite self-renewal, differentiate into various types of cells and secrete protective paracrine factors, many researchers have investigated the potential of SCT in regenerative medicine. Therefore, this review aims to provide a comprehensive review on the recent application of SCT in various intractable diseases, namely, haematological diseases, neurological diseases, diabetes mellitus, retinal degenerative disorders and COVID-19 infections along with the challenges faced in the clinical translation of SCT. Methods: An extensive search was conducted on Google scholar, PubMed and Clinicaltrials.gov using related keywords. Latest articles on stem cell therapy application in selected diseases along with their challenges in clinical applications were selected. Key content and findings: In vitro and in vivo studies involving SCT are shown to be safe and efficacious in treating various diseases covered in this review. There are also a number of small-scale clinical trials that validated the positive therapeutic outcomes of SCT. Nevertheless, the effectiveness of SCT are highly variable as some SCT works best in patients with early-stage diseases while in other diseases, SCT is more likely to work in patients in late stages of illnesses. Among the challenges identified in SCT translation are uncertainty in the underlying stem cell mechanism, ethical issues, genetic instability and immune rejection. Conclusions: SCT will be a revolutionary treatment in the future that will provide hope to patients with intractable diseases. Therefore, studies ought to be done to ascertain the long-term effects of SCT while addressing the challenges faced in validating SCT for clinical use. Moreover, as there are many studies investigating the safety and efficacy of SCT, future studies should look into elucidating the regenerative and reparative capabilities of stem cells which largely remains unknown.

14.
J Genet Eng Biotechnol ; 20(1): 106, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35838847

ABSTRACT

BACKGROUND: In recent years, major advance in molecular biology and genomic technologies have led to an exponential growth in biological information. As the deluge of genomic information, there is a parallel growth in the demands of tools in the storage and management of data, and the development of software for analysis, visualization, modelling, and prediction of large data set. MAIN BODY: Particularly in plant biotechnology, the amount of information has multiplied exponentially with a large number of databases available from many individual plant species. Efficient bioinformatics tools and methodologies are also developed to allow rapid genome sequence and the study of plant genome in the 'omics' approach. This review focuses on the various bioinformatic applications in plant biotechnology, and their advantages in improving the outcome in agriculture. The challenges or limitations faced in plant biotechnology in the aspect of bioinformatics approach that explained the low progression in plant genomics than in animal genomics are also reviewed and assessed. CONCLUSION: There is a critical need for effective bioinformatic tools, which are able to provide longer reads with unbiased coverage in order to overcome the complexity of the plant's genome. The advancement in bioinformatics is not only beneficial to the field of plant biotechnology and agriculture sectors, but will also contribute enormously to the future of humanity.

15.
Rep Biochem Mol Biol ; 11(1): 125-137, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35765526

ABSTRACT

Background: It is believed that activation of microglia in the central nervous system upon detection of stimulus like lipopolysaccharides provokes neuroinflammation via the production of pro-inflammatory mediators and cytokines. The cytoprotective and anti-inflammatory properties of various folk medicine has been gaining attention as a strategy to combat various disease. This study aimed to assess the anti-neuroinflammatory properties of chloroform extract of in vitro Panax ginseng root culture based on nitric oxide and cytokines production. Methods: The study was initiated with the determination of maximum non-toxic dose (MNTD) of P. ginseng root culture chloroform extract using the MTT assay. The lipopolysaccharides-stimulated BV2 microglia cells were treated with MNTD and ½MNTD of the extract and its anti-neuroinflammatory properties were assessed by measuring the production of nitric oxide (NO) via Griess assay, as well as TNF-α, IL-6 and IL-10 using Quantikine ELISA. Results: It was found that the MNTD and ½MNTD of the extract did not play a significant role in the production of pro-inflammatory cytokines such as NO, TNF-α and IL-6. However, the MNTD and ½MNTD of chloroform extract significantly increased the anti-inflammatory IL-10 compared to the untreated cells. Conclusion: With this, the chloroform extract of P. ginseng root culture potentially exerts anti-neuroinflammatory properties.

16.
Biosens Bioelectron ; 208: 114234, 2022 Jul 15.
Article in English | MEDLINE | ID: mdl-35397328

ABSTRACT

Chronic kidney disease (CKD) is the most neglected chronic disease affecting over 750 million persons in the world. Currently, many patients with cancers or other chronic diseases (i.e., CKD) struggle to receive clinical treatment or examination due to hospitals cancelling or delaying in the COVID-19 pandemic, which may increase the risk of death. Cystatin C (Cys C) has been proposed as a potential glomerular filtration rate (GFR) marker for the early detection of acute kidney injury and CKD. However, most traditional methods for Cys C detection are immunoassays using serum as a sample and are tedious to perform and economically burdensome. To diagnose the disease in the early stage and carry out daily management during the current pandemic, we developed an integration of hydrogel microneedle patch (HMNP) and lateral flow cassette (LFC) to rapidly detect Cys C in skin interstitial fluid (ISF) in 25 min for blood-free CKD management anytime and anywhere by the naked eye that can reduce the impact of an individual's quality of life and life expectancy. Conceivably, this strategy presents a wide scope in the application of numerous other diseases if corresponding analytes are available in skin ISF.


Subject(s)
Biosensing Techniques , COVID-19 , Renal Insufficiency, Chronic , COVID-19/diagnosis , Creatinine , Female , Humans , Male , Pandemics , Point-of-Care Testing , Quality of Life , Renal Insufficiency, Chronic/diagnosis
17.
Mol Cancer Ther ; 21(2): 257-270, 2022 02.
Article in English | MEDLINE | ID: mdl-34789561

ABSTRACT

α-Mangostin (aMan) and Paeonol (Pae) have shown anticancer and anti-inflammatory properties. However, these two natural compounds have no clinical value because of their low solubility and low membrane permeability. In this study, we screened chemically synthesized derivatives from these two natural compounds as potential novel chemicals that increase cancer cell cytotoxicity over nontransformed human cells. We found that two derivative compounds, named α-Mangostin-1 (aMan1) and Paeonol-1 (Pae1) more efficiently and more specifically induced cytotoxicity in HCT116, HT29, and SW48 colorectal cancer cell lines than the parental compounds. Both aMan1 and Pae1 arrested HCT116 cells in the G1 phase and HT29 and SW48 cells in the G2-M phase of the cell cycle. Both aMan1 and Pae1 induced apoptosis in human colorectal cancer cells, through a caspase-dependent mechanism. aMan1 and Pae1 induced selective transcriptional responses in colorectal cancer cells involving genes related to metabolic stress and DNA damage response signaling pathways. Finally, experiments on primary colon organoids showed that both derivatives were able to kill cancer-derived organoids without affecting the viability of organoids derived from healthy tissue, where the parental compounds and the currently used chemotherapeutic drug irinotecan failed. In conclusion, our findings expand the knowledge of natural compound derivatives as anticancer agents and open new avenues of research in the derivation of lead compounds aimed at developing novel chemotherapeutic drugs for colorectal cancer treatment that selectively target cancer, but not healthy cells.


Subject(s)
Acetophenones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Xanthones/therapeutic use , Acetophenones/pharmacology , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Cell Proliferation , Humans , Protein Kinase Inhibitors/pharmacology , Xanthones/pharmacology
18.
Front Oncol ; 12: 1096411, 2022.
Article in English | MEDLINE | ID: mdl-36686723

ABSTRACT

Background: Retroperitoneal liposarcoma (RPLS) is a rare malignancy that is notorious for recurrence. Surgical resection with clean margin is the current treatment of choice. However, owing to the large retroperitoneal space, RPLSs often grow to significant sizes before being diagnosed. Neoadjuvant and adjuvant therapies have potentials to improve long term treatment outcome. Case presentation: A 55-year-old Han Chinese male presented to the general surgery department with a one-year history of abdominal fullness and a one-week history of palpable right inguinal mass. At first, he was diagnosed with incarcerated inguinal hernia. However, abdominal computer tomography (CT) and biopsy confirmed his final diagnosis to be retroperitoneal well-differentiated liposarcoma, cT2bN0M0, stage IIb. The tumor, which measured 44.5cm in maximum diameter, was too large for primary surgical resection. Neoadjuvant radiotherapy with 70 Gy in 35 fractions was delivered to the tumor, which shrunk the target volume from 6300 cc to 4800 cc, as observed in the middle of the radiotherapy course. The right testicular mass also received 70Gy/35Fx. Conversion surgery was performed after radiotherapy. Unfortunately, due to residual tumor, adjuvant chemotherapy consisting of AIM (ifosfamide, Mesna, and doxorubicin) and MAID (Mesna, doxorubincin, ifosfamide, and dacarbazine) regimens were administered sequentially. Afterward, debulking surgery was conducted, plus another 18 cycles of ifosfamide monotherapy when residual tumor was still seen on CT. Since the completion of ifosfamide chemotherapy, the patient has been cancer free with no evidence of tumor recurrence for more than 26 months. Conclusion: Despite conflicting evidence in the literature, our case supports the use of high dose neoadjuvant radiotherapy and adjuvant chemotherapy in treating large, unresectable RPLSs. It also highlights the importance of using individualized, multidisciplinary approach in achieving cure for large, unresectable rare tumors.

19.
J Clin Hypertens (Greenwich) ; 23(7): 1413-1419, 2021 07.
Article in English | MEDLINE | ID: mdl-34105885

ABSTRACT

The aim of the present study was to explore the relationship between androgen and LVH in postmenopausal hypertensive women. Enrolled in this study were 378 postmenopausal hypertensive women who were admitted to the department of cardiology between December 2018 and December 2020. According to left ventricular mass index (LVMI) evaluated by echocardiography, the patients were divided into LVH group (n = 172) and non-LVH group (n = 206). Their clinical characteristics were collected. Based on the result of propensity score matching analysis, 160 cases in each group were matched successfully. After correcting for confounding factors by various models, the results showed that free androgen index (FAI) and sex hormone-binding globulin (SHBG) were the influencing factors of LVH in postmenopausal women with hypertension. Patients with elevated SHBG were 5% less likely to develop LVH than those without elevated SHBG (OR: 0.950, 95% CI 0.922-1.578). Postmenopausal hypertensive patients with elevated FAI were 16% more likely to have LVH than those without elevated FAI (OR: 1.608, 95% CI 0.807-3.202). Multiple linear regression showed that LVMI increased by 61.82g/m2 for every 1 unit increase in FAI. In addition, SHBG decreased by 1 nmol/l, and LVMI increased by 0.177g/m2 . Subgroup analysis showed that patients in the controlled BP group had a lower risk of LVH for every additional unit of SHBG compared with the uncontrolled BP group. The risk of LVH for each additional unit of FAI in the uncontrolled BP group was higher than that in the controlled BP group. The results of this present study showed that the occurrence of LVH was positively correlated with FAI and negatively correlated with SHBG in postmenopausal women with hypertension. The increase in FAI level and the decrease in SHBG level may be related to the occurrence and development of LVH in postmenopausal hypertension.


Subject(s)
Hypertension , Sex Hormone-Binding Globulin , Androgens , Female , Humans , Hypertension/epidemiology , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/epidemiology , Postmenopause
20.
J Tradit Chin Med ; 41(2): 185-193, 2021 04.
Article in English | MEDLINE | ID: mdl-33825397

ABSTRACT

OBJECTIVE: To investigate the anti-neuroinflammatory properties of Panax ginseng (P. ginseng) root by measuring the levels of nitric oxide (NO), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. METHODS: Maximal non-toxic dose (MNTD) of methanol extract of P. ginseng root culture on BV2 microglia cells was first determined via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, followed by treatment and LPS stimulation of cells, and the measurement of NO using Griess assay and TNF-α, IL-6, and IL-10 using ELISA assay. RESULTS: The MNTD of P. ginseng root extract was determined to be (587 ± 57) µg/mL. Following that, NO and IL-6 levels were found to be insignificantly reduced by 6.88% and 0.14% respectively in stimulated cells upon treatment with MNTD. Treatment with MNTD yielded similar insignificant result, with only a reduction of 3.58% and 0.08% in NO and IL-6 levels respectively. However, TNF-α and IL-10 levels were significantly downregulated by 15.64% and 34.96% respectively upon treatment with P. ginseng root extract at MNTD. CONCLUSION: Methanol extract of P. ginseng root culture did not show any significant anti-inflammatory effects on NO and IL-6 levels, but might potentially possess both anti-neuroinflammatory and pro-neuroinflammatory properties through the downregulation of TNF-α and IL-10 respectively.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Drugs, Chinese Herbal/pharmacology , Inflammation/drug therapy , Microglia/drug effects , Panax/chemistry , Animals , Cyclooxygenase 2/genetics , Cyclooxygenase 2/immunology , Humans , Inflammation/genetics , Inflammation/immunology , Lipopolysaccharides/adverse effects , Microglia/immunology , NF-kappa B/genetics , NF-kappa B/immunology , Nitric Oxide/immunology , Plant Roots/chemistry
SELECTION OF CITATIONS
SEARCH DETAIL
...