ABSTRACT
BACKGROUND: Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow associated with high mortality. Although several effective therapies have been developed to reduce symptoms in patients with CML, many of these methods are associated with side effects. Coreopsis tinctoria Nutt. (C. tinctoria) is a natural medicinal material that possesses antioxidant and anticancer activities. Yet, its effect in treating leukemia has still not been fully explored. OBJECTIVE: To optimize the C. tinctoria flower extraction process and investigate whether these extracts can impair CML cell survival. METHODS: The extraction process of C. tinctoria was optimized by the Box-Behnken design response surface method. K562 cells were treated with different volumes (0, 10, 25, 50, and 100 µL) of C. tinctoria flower extracts. The effect of C. tinctoria extract on cell morphology and cell apoptosis was assessed by light microscopy, laser confocal microscopy, and flow cytometry. RESULTS: We established the following optimized C. tinctoria flower extraction conditions: temperature of 84.4 °C, extraction period of 10 mins, solid-liquid ratio of 1:65, and times 4. These conditions were applied for C. tinctoria flower extraction. Pre-incubation of extracts prepared under the aforementioned optimal conditions with K562 cells induced cell cytotoxicity and cell apoptosis. CONCLUSION: C. tinctoria flower extracts exert obvious anti-leukemia effects in vitro and may be a potential drug candidate for leukemia treatment.
ABSTRACT
Alzheimer's disease (AD) is the most common neurodegenerative disease, which is mainly caused by the damage of the structure and function of the central nervous system. At present, there are many adverse reactions in market-available drugs, which can't significantly inhibit the occurrence of AD. Therefore, the current focus of research is to find safe and effective therapeutic drugs to improve the clinical treatment of AD. Oxidative stress bridges different mechanism hypotheses of AD and plays a key role in AD. Numerous studies have shown that natural flavonoids have good antioxidant effects. They can directly or indirectly resist -oxidative stress, inhibit Aß aggregation and Tau protein hyperphosphorylation by activating Nrf2 and other oxidation-antioxidation-related signals, regulating synaptic function-related pathways, promoting mitochondrial autophagy, etc., and play a neuroprotective role in AD. In this review, we summarised the mechanism of flavonoids inhibiting oxidative stress injury in AD in recent years. Moreover, because of the shortcomings of poor biofilm permeability and low bioavailability of flavonoids, the advantages and recent research progress of nano-drug delivery systems such as liposomes and solid lipid nanoparticles were highlighted. We hope this review provides a useful way to explore safe and effective AD treatments.
ABSTRACT
BACKGROUND: Early pregnancy is a critical window for neural system programming; however, the association of first-trimester fetal size with children's neurodevelopment remains to be assessed. This study aimed to explore the association between first-trimester fetal size and children's neurodevelopment and to examine whether intrauterine accelerated growth could compensate for the detrimental effects of first-trimester restricted growth on childhood neurodevelopment. METHODS: The participants were from a birth cohort enrolled from March 2014 to March 2019 in Wuhan, China. A total of 2058 fetuses with crown to rump length (CRL) (a proxy of first-trimester fetal size) measurements in the first trimester and neurodevelopmental assessment at age 2 years were included. We measured the first-trimester CRL and defined three fetal growth patterns based on the growth rate of estimated fetal weight from mid to late pregnancy. The neurodevelopment was assessed using the Bayley Scales of Infant Development of China Revision at 2 years. RESULTS: Each unit (a Z score) increase of first-trimester CRL was associated with increased scores in mental developmental index (MDI) (adjusted beta estimate = 1.19, (95% CI: 0.42, 1.95), P = 0.03) and psychomotor developmental index (PDI) (adjusted beta estimate = 1.36, (95% CI: 0.46, 2.26), P < 0.01) at age 2 years, respectively. No significant association was observed between fetal growth rate and PDI. For children with restricted first-trimester fetal size (the lowest tertile of first-trimester CRL), those with "intrauterine accelerated growth" pattern (higher growth rates) had significantly higher MDI (adjusted beta estimate = 6.14, (95% CI: 3.80, 8.49), P < 0.001) but indistinguishable PDI compared to those with "intrauterine faltering growth" pattern (lower growth rates). Main limitations of this study included potential misclassification of gestational age due to recall bias of the last menstrual period and residual confounding. CONCLUSIONS: The current study suggests that restricted first-trimester fetal size is associated with mental and psychomotor developmental delay in childhood. However, in children with restricted first-trimester fetal size, intrauterine accelerated growth was associated with improved mental development but had little effect on psychomotor development. Additional studies are needed to validate the results in diverse populations.
Subject(s)
Child Development , Fetal Development , Pregnancy Trimester, First , Humans , Female , Pregnancy , Fetal Development/physiology , Child, Preschool , Child Development/physiology , China , Male , Cohort Studies , Adult , Crown-Rump LengthABSTRACT
Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.
Subject(s)
Root Canal Filling Materials , Root Canal Therapy , Humans , Consensus , Root Canal Therapy/methods , Gutta-Percha/therapeutic use , Dental Pulp Necrosis/drug therapy , Retreatment , Dental Pulp Cavity , Root Canal Filling Materials/therapeutic use , Root Canal PreparationABSTRACT
Objective: This study aimed to assess the impact of combined moxibustion therapy and Gua sha on enhancing functional independence, reducing fall risk, and alleviating pain in patients undergoing post-rehabilitation for multiple cerebral infarctions. Methods: In a prospective clinical trial, 67 patients diagnosed with multiple cerebral infarctions (age range: 40 to 93 years) were enrolled. Baseline health characteristics included a median hospital stay of 10 days, prevalent medical conditions such as hypertension (64.18%), and various comorbidities like spondylosis (17.91%) and heart disease (14.93%). Patients received moxibustion treatment daily for 20-30 minutes on specific acupoints of the upper and lower extremities. Additionally, Gua sha therapy targeting the the head, back, chest, abdomen, and selected acupoints was administered twice a week with an interval of 3 to 4 days. Assessments included Barthel Index (BI) for functional independence, Morse Fall Scale (MFS) for fall risk, and Visual Analogue Scale (VAS) for pain intensity before and after the intervention. Results: After one week of rehabilitation, significant improvements were observed in the patient's functional independence, as indicated by a median BI score of 100 (IQR: 95-100), compared to the pre-rehabilitation median score of 95 (IQR: 90-100). The MFS score also showed a significant decrease after rehabilitation, with a median score of 35 (IQR: 35-45) compared to the pre-rehabilitation median score of 45 (IQR: 35-45). Additionally, pain intensity significantly decreased, with a median VAS score of 0 (range: 0-2) after rehabilitation, compared to the pre-rehabilitation median score of 0 (range: 0-3). Conclusion: Combined moxibustion therapy and Gua sha demonstrated positive effects on functional independence, fall risk reduction, and pain alleviation in post-rehabilitation for multiple cerebral infarctions. These findings suggest the potential of moxibustion and Gua sha as complementary interventions in stroke rehabilitation. The observed improvements in functional independence, fall risk, and pain underscore the potential benefits of these therapies for patients with multiple cerebral infarctions. Further exploration could delve into long-term effects, larger-scale trials, and mechanistic studies to elucidate the underlying pathways of efficacy.
ABSTRACT
The repair of mandibular defects is a challenging clinical problem, and associated infections often hinder the treatment, leading to failure in bone regeneration. Herein, a multifunctional platform is designed against the shortages of existing therapies for infected bone deficiency. 2D Ti3C2 MXene and berberine (BBR) are effectively loaded into 3D printing biphasic calcium phosphate (BCP) scaffolds. The prepared composite scaffolds take the feature of the excellent photothermal capacity of Ti3C2 as an antibacterial, mediating NIR-responsive BBR release under laser stimuli. Meanwhile, the sustained release of BBR enhances its antibacterial effect and further accelerates the bone healing process. Importantly, the integration of Ti3C2 improves the mechanical properties of the 3D scaffolds, which are beneficial for new bone formation. Their remarkable biomedical performances in vitro and in vivo present the outstanding antibacterial and osteogenic properties of the Ti3C2-BBR functionalized BCP scaffolds. The synergistic therapy makes it highly promising for repairing infected bone defects and provides insights into a wide range of applications of 2D nanosheets in biomedicine.
Subject(s)
Berberine , Hydroxyapatites , Nitrites , Tissue Scaffolds , Transition Elements , Berberine/pharmacology , Bone Regeneration , Anti-Bacterial Agents/pharmacology , Printing, Three-DimensionalABSTRACT
Coreopsis tinctoria Nutt. (C. tinctoria) is a traditional medicinal plant, primarily found in plateau areas with altitudes exceeding 3000 m. The efficacy of C. tinctoria appears to be intricately tied to its quality. However, there is a scarcity of studies focused on evaluating the quality of C. tinctoria from diverse geographical locations. In this study, we used ultra-performance liquid chromatography-quadrupole time-of-flight-tandem mass spectrometry to analyze and identify the prevalent chemical components in 12 batches of C. tinctoria sourced from Xinjiang, Qinghai, Tibet, and Yunnan provinces in China. By using cluster analysis and discriminant analysis of partial least squares, we assessed the similarity and identified varying components in the 12 batches of C. tinctoria. Subsequently, their quality was further evaluated. Utilizing network pharmacology, we identified potential active components for the treatment of diabetes mellitus. The findings revealed the presence of 16 flavonoids, 3 phenylpropanes, 2 sugars, 2 amino acids, and 7 hydrocarbons in the analyzed samples. Through variable importance screening, 17 constituents were identified as quality difference markers. Marein and flavanomarein emerged as pivotal markers, crucial for distinguishing variations in C. tinctoria. In addition, network pharmacology predicted 187 targets for 9 common active components, including marein and flavanomarein. Simultaneously, 1747 targets related to diabetes mellitus were identified. The drug-component-disease target network comprised 91 nodes and 179 edges, encompassing 1 drug node, 9 component nodes, and 81 target nodes. In summary, marein and flavanomarein stand out as key biomarkers for assessing the quality of C. tinctoria, offering a scientific foundation for the quality evaluation of C. tinctoria Nutt.
Subject(s)
Chalcones , Coreopsis , Diabetes Mellitus , Coreopsis/chemistry , Tandem Mass Spectrometry , Chemometrics , Chromatography, High Pressure Liquid , Network Pharmacology , ChinaABSTRACT
Air pollution exposure was known to result in body impairments by inducing inflammation and oxidation. But little is known about the associations of air pollutants with plasma fatty acid profile which may play important roles in the impairment of air pollutants based on the related mechanism, especially in pregnant women. This study aimed to explore the relationships of air pollution exposure with plasma fatty acid profile and the potential effect modification by pre-pregnancy body mass index (BMI). Based on a cohort in Wuhan, China, we measured concentrations of plasma fatty acids of 519 pregnant women enrolled from 2013 to 2016 by gas chromatography-mass spectrometry (GC-MS). Levels of exposure to air pollutants (fine particulate matter (PM2.5), inhalable particles (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO)) were estimated by using spatial-temporal land use regression models and calculated in three periods (average concentrations during 1 day, 1 week, and 1 month before the phlebotomizing day in the first trimester). Per interquartile range increment of the levels of air pollution exposure 1 day before phlebotomizing was related to 1.21-2.01% increment of omega-6 polyunsaturated fatty acids (n-6PUFA) and 0.63-1.74% decrement of omega-3 polyunsaturated fatty acids (n-3PUFA). Besides, relationships above were kept robust in the analysis during 1 week and 1 month before phlebotomizing. In women with normal BMI, plasma fatty acid profile was observed to be more sensitive to air pollutants. Our study demonstrated that increment of exposure to air pollutants was associated with higher plasma n-6PUFA known to be pro-inflammatory and lower plasma n-3PUFA known to be anti-inflammatory, which was more sensitive in pregnant women with normal BMI. Our findings suggested that changes in plasma fatty acid profile should cause concerns and may serve as biomarkers in the further studies. Future studies are needed to validate our findings and elucidate the underlying mechanisms.
Subject(s)
Air Pollutants , Air Pollution , Humans , Female , Pregnancy , Pregnant Women , Cohort Studies , Air Pollution/analysis , Air Pollutants/analysis , Particulate Matter/analysis , Fatty Acids/analysis , Fatty Acids, Unsaturated , China , Nitrogen Dioxide/analysisABSTRACT
Phototherapy, which generally refers to photothermal therapy (PTT) and photodynamic therapy (PDT), has received significant attention over the past few years since it is non-invasive, has effective selectivity, and has few side effects. As a result, it has become a promising alternative to traditional clinical treatments. At present, two-dimensional materials (2D materials) have proven to be at the forefront of the development of advanced nanomaterials due to their ultrathin structures and fascinating optical properties. As a result, much work has been put into developing phototherapy platforms based on 2D materials. This review summarizes the current developments in 2D materials beyond graphene for phototherapy, focusing on the novel approaches of PTT and PDT. New methods are being developed to go above and beyond conventional treatment to fully use the potential of 2D materials. Additionally, the efficacy of cutting-edge phototherapy is assessed, and the existing difficulties and future prospects of 2D materials for phototherapy are covered.
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Piper longum L., an herbal medicine used in India and other Asian countries, is prescribed routinely for a range of diseases, including tumor. Piperlongumine, a natural product isolated from Piper longum L., has received widespread attention due to its various pharmacological activities, such as anti-inflammatory, antimicrobial, and antitumor effects. AIM OF THE STUDY: Chronic myelogenous leukemia (CML) is a hematopoietic disease caused by Bcr-Abl fusion gene, with an incidence of 15% in adult leukemias. Targeting Bcr-Abl by imatinib provides a successful treatment approach for CML. However, imatinib resistance is an inevitable issue for CML treatment. In particular, T315I mutant is the most stubborn of the Bcr-Abl point mutants associated with imatinib resistance. Therefore, it is urgent to find an alternative approach to conquer imatinib resistance. This study investigated the role of a natural product piperlongumine in overcoming imatinib resistance in CML. MATERIALS AND METHODS: Cell viability and apoptosis were evaluated by MTS assay and Annexin V/propidium iodide counterstaining assay, respectively. Levels of intracellular signaling proteins were assessed by Western blots. Mitochondrial membrane potential was reflected by the fluorescence intensity of rhodamine-123. The function of proteasome was detected using 20S proteasomal activity assay, proteasomal deubiquitinase activity assay, and deubiquitinase active-site-directed labeling. The antitumor effects of piperlongumine were assessed with mice xenografts. RESULTS: We demonstrate that (i) Piperlongumine inhibits proteasome function by targeting 20S proteasomal peptidases and 19S proteasomal deubiquitinases (USP14 and UCHL5) in Bcr-Abl-WT and Bcr-Abl-T315I CML cells; (ii) Piperlongumine inhibits the cell viability of CML cell lines and primary CML cells; (iii) Proteasome inhibition by piperlongumine leads to cell apoptosis and downregulation of Bcr-Abl; (iv) Piperlongumine suppresses the tumor growth of CML xenografts. CONCLUSIONS: These results support that blockade of proteasome activity by piperlongumine provides a new therapeutic strategy for treating imatinib-resistant CML.
Subject(s)
Antineoplastic Agents , Biological Products , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Mice , Animals , Imatinib Mesylate/pharmacology , Imatinib Mesylate/therapeutic use , Proteasome Endopeptidase Complex/metabolism , Drug Resistance, Neoplasm , Cell Proliferation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Fusion Proteins, bcr-abl/genetics , Apoptosis , Deubiquitinating Enzymes/therapeutic use , Biological Products/therapeutic use , Cell Line, Tumor , Antineoplastic Agents/pharmacology , Ubiquitin Thiolesterase/therapeutic useABSTRACT
The variable dosage forms of most traditional Chinese medicines (TCMs) could be disadvantaged by low selectivity, poor biological distribution, limited bioavailability with low efficacy, and some adverse effects. These issues limit the control of clinical pharmacodynamics of the antitumor active components. With the progress of science and technology, many new polymer materials and new technologies have emerged, such as nanotechnology, cyclodextrin inclusion, solid dispersion, microcapsule and microsphere technologies. These new technologies provide a good basis for exploring novel TCM dosage forms for overcoming the shortcomings. The increased numbers of new technologies have been used to study TCM dosage forms with remarkable achievements. In this review paper, we will provide a systematic overview of the new dosage forms of nano-formulations and co-medications in relation to nano-delivery systems in an attempt to provide useful references for practical application of active antitumor ingredients from the TCMs.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Drug Delivery Systems , Nanotechnology , ChinaABSTRACT
BACKGROUND: Chronic myeloid leukaemia (CML) is a haematological cancer featured by the presence of BCR-ABL fusion protein with abnormal tyrosine kinase activation. Classical tyrosine kinase inhibitor (TKI)-based therapies are available to patients with CML. However, acquired resistance to TKI has been a challenging obstacle, especially stubborn T315I mutation is the most common cause. Therefore, it is especially urgent to find more effective targets to overcome TKI resistance induced by BCR-ABLT315I . Proteasomal deubiquitinases (USP14 and UCHL5) have fundamental roles in the ubiquitin-proteasome system and possess multiple functions during cancer progression. METHODS: The human peripheral blood mononuclear cells were collected to measure the mRNA expression of USP14 and UCHL5, as well as to detect the toxicity effect of b-AP15. We explored the effect of b-AP15 on the activity of proteasomal deubiquitinases. We detected the effects of b-AP15 on BCR-ABLWT and BCR-ABLT315I CML cells in vitro and in the subcutaneous tumour model. We knocked down USP14 and/or UCHL5 by shRNA to explore whether these proteasomal deubiquitinases are required for cell proliferation of CML. RESULTS: In this study, we found that increased expression of the proteasomal deubiquitinase USP14 and UCHL5 in primary cancer cells from CML patients compared to healthy donors. b-AP15, an inhibitor of USP14 and UCHL5, exhibited potent tumour-killing activity in BCR-ABLWT and BCR-ABLT315I CML cell lines, as well as in CML xenografts and primary CML cells. Mechanically, pharmacological or genetic inhibition of USP14 and UCHL5 induced cell apoptosis and decreased the protein level of BCR-ABL in CML cells expressing BCR-ABLWT and BCR-ABLT315I . Moreover, b-AP15 synergistically enhanced the cytotoxic effect caused by TKI imatinib in BCR-ABLWT and BCR-ABLT315I CML cells. CONCLUSION: Collectively, our results demonstrate targeting USP14 and UCHL5 as a potential strategy for combating TKI resistance in CML.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Proteasome Endopeptidase Complex , Protein Kinase Inhibitors , Ubiquitin Thiolesterase , Deubiquitinating Enzymes/genetics , Deubiquitinating Enzymes/therapeutic use , Drug Resistance, Neoplasm/genetics , Fusion Proteins, bcr-abl/genetics , Fusion Proteins, bcr-abl/metabolism , Fusion Proteins, bcr-abl/pharmacology , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/pathology , Piperidones/metabolism , Piperidones/pharmacology , Proteasome Endopeptidase Complex/genetics , Proteasome Endopeptidase Complex/metabolism , Proteasome Endopeptidase Complex/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/geneticsABSTRACT
Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) are refractory or relapse to standard chemotherapy, and most of them are activated B cell-like DLBCLs (ABC-DLBCL) and germinal center B cell-like DLBCLs (GCB-DLBCL). SNS-032, a novel and selective CDK7/9 inhibitor, that the first phase clinical trials approved by US FDA for cancer treatment have been completed. In this study, we investigated the anti-tumor effect of SNS-032 in ABC- and GCB-DLBCL subtypes. We report that SNS-032 induced growth inhibition and cell apoptosis in both DLBCL cells in vitro, and inhibited the growth of both DLBCL xenografts in nude mice. Mechanistically, SNS-032 inhibited RNA polymerase II, which led to transcriptional-dependent suppression of NF-κB signaling pathway and its downstream targets involved in cell survival; SNS-032 also downregulates BCL-2 and c-MYC in both mRNA and protein levels. Significantly, these findings provide pre-clinical evidence for application of targeting the CDK7/9 in DLBCL.
Subject(s)
Lymphoma, Large B-Cell, Diffuse , Neoplasm Recurrence, Local , Animals , Apoptosis , Cyclin-Dependent Kinases , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Mice , Mice, Nude , Oxazoles , ThiazolesABSTRACT
BACKGROUND: Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. METHODS: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). RESULTS: Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. CONCLUSIONS: This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.
Subject(s)
Albumin-Bound Paclitaxel/pharmacology , Antineoplastic Agents/pharmacology , Albumin-Bound Paclitaxel/administration & dosage , Albumin-Bound Paclitaxel/adverse effects , Albumin-Bound Paclitaxel/pharmacokinetics , Animals , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Cell Line, Tumor , Cell Proliferation , Chemistry, Pharmaceutical , Drug Carriers , Drug Liberation , Drug Stability , Female , Mice , Mice, Inbred ICR , Nanoparticles , Particle Size , Random Allocation , Surface PropertiesABSTRACT
BACKGROUND: Positioning stent in head and neck radiotherapy seems to have benefit to prevent oral complications but it hasn't been summarized by an evidence-based method. OBJECTIVES: This review aims to evaluate the efficacy of positioning stents in preventing oral complications after radiotherapy. METHODS: We conducted an electronic search in MEDLINE, EMBASE, Cochrane CDSR, and Cochrane CENTRAL database for randomized-controlled clinical trials, controlled clinical trials and cohort studies that assessed oral complications after head and neck radiotherapy with positioning stents. Two reviewers extracted information on radiotherapy, follow-up period, oral complications and assessments independently. RESULTS: Three RCTs and two cohort studies were included in this review. Oral complications such as mucositis, xerostomia, taste alteration, trismus, salivary changes, dysphagia and pain on swallowing were assessed by different methods in these studies. CONCLUSIONS: Oral complications were common in patients after head and neck radiotherapy. There is insufficient evidence that positioning stents have a preventive effect against xerostomia, and it needs more high-quality and prospective trials with long-term follow-up to support it.
Subject(s)
Head and Neck Neoplasms/radiotherapy , Mouth Diseases/prevention & control , Radiation Injuries/prevention & control , Stents , Humans , Mouth Diseases/etiology , Organs at Risk/radiation effects , Radiation Injuries/etiology , Radiation Protection/instrumentation , Treatment OutcomeABSTRACT
Bone-metastasis prostate cancer (BMPCa)-targeting gene therapy is gaining increasing concern in recent years. The peptide T7-modified polypeptide nanoparticles for delivery DNA (CRD-PEG-T7/pPMEPA1) was prepared as our previous study. However, the feasibility of CRD-PEG-T7/pPMEPA1 for BMPCa treatment, the mechanisms underlying cellular uptake, anti-BMPCa effect, and administration safety requires further research. LNCaP cells treated with endocytosis inhibitors and excessive T7 under different culture condition were carried out to investigate the mechanisms of cellular uptake of the CRD-PEG-T7-pPMEPA1. A transwell assay was applied to evaluate the cell migration ability. Besides, the tumor volume and survival rates of the PCa xenograft mice model were recorded to estimate the anti-tumor effect. In addition, the weight profiles of the PCa tumor-bearing mice, the blood chemistry, and the HE analysis of visceral organs and tumor was conducted to investigate the administration safety of CRD-PEG-T7/pPMEPA1. The results showed that PCa cellular uptake was decreased after treating with excessive free T7, endocytosis inhibitors and lower incubation temperature. Besides, CRD-PEG-T7/pPMEPA1 could inhibit the LNCaP cells chemotaxis and tumor growth. In addition, the survival duration of the PCa tumor-bearing mice treating with CRD-PEG-T7/pPMEPA1 was significantly prolonged with any systemic toxicity or damage to the organs. In conclusion, this research proposes a promising stratagem for treatment BMPCa by providing the biocompatible and effective carrier for delivery DNA therapeutic agents.
Subject(s)
Bone Neoplasms/prevention & control , Bone Neoplasms/secondary , Genetic Vectors/chemistry , Genetic Vectors/pharmacology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Animals , Arginine , Aspartic Acid , Cell Line, Tumor , Cell Movement , Cell Survival , Cysteine , Male , Membrane Proteins/genetics , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Particle Size , Peptide Fragments , Peptide T , Polyethylene Glycols/chemistry , Tumor BurdenABSTRACT
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. The prognosis of HCC remains very poor; thus, an effective treatment remains urgent. Herein, a type of nanomedicine is developed by conjugating Fe@Fe3 O4 nanoparticles with ginsenoside Rg3 (NpRg3), which achieves an excellent coupling effect. In the dimethylnitrosamine-induced HCC model, NpRg3 application significantly prolongs the survival of HCC mice. Further research indicates that NpRg3 application significantly inhibits HCC development and eliminates HCC metastasis to the lung. Notably, NpRg3 application delays HCC-induced ileocecal morphology and gut microbial alterations more than 12 weeks during HCC progression. NpRg3 administration elevates the abundance of Bacteroidetes and Verrucomicrobia, but decreases Firmicutes. Twenty-nine predicted microbial gene functions are enriched, while seven gene functions are reduced after NpRg3 administration. Moreover, the metabolomics profile presents a significant progression during HCC development, but NpRg3 administration corrects tumor-dominant metabolomics. NpRg3 administration decreases 3-indolepropionic acid and urea, but elevates free fatty acids. Importantly, NpRg3 application remodels the unbalanced correlation networks between gut microbiota and metabolism during HCC therapy. In conclusion, nanoparticle conjugation of ginsenoside Rg3 inhibits HCC development and metastasis via the remodeling of unbalanced gut microbiota and metabolism in vivo, providing an antitumor therapy strategy.