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1.
Clin Cancer Res ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38995268

ABSTRACT

PURPOSE: To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study. EXPERIMENTAL DESIGN: Plasma samples were collected for serial ctDNA profiling at baseline (Cycle 1 Day 1 prior to treatment) and multiple on-treatment time points (Cycle 1 Day 15 and Cycle 3 Day 1). RESULTS: KRAS G12C ctDNA was detectable from plasma samples in 72.9% (43/59) and 92.6% (50/54) of patients with non-small cell lung cancer and colorectal cancer, respectively, the majority of whom were eligible for study participation based on a local test detecting the KRAS G12C mutation in tumor tissue. Baseline ctDNA tumor fraction was associated with tumor type, disease burden, and metastatic sites. A decline in ctDNA level was observed as early as Cycle 1 Day 15. Serial assessment showed a decline in ctDNA tumor fraction associated with response and progression-free survival. Except for a few cases of KRAS G12C sub-clonality, on-treatment changes in KRAS G12C variant allele frequency mirrored changes in the overall ctDNA tumor fraction. CONCLUSION: Across tumor types, the KRAS G12C mutation likely represents a truncal mutation in the majority of patients. Rapid and deep decline in ctDNA tumor fraction was observed in patients responding to divarasib treatment. Early on-treatment dynamics of ctDNA were associated with patient outcomes and tumor response to divarasib treatment.

2.
Fitoterapia ; 177: 106110, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38977253

ABSTRACT

Six previously undescribed meroterpenoids, penicianstinoids F-K (1-6), together with four known analogues, dehydroaustinol (7), dehydroaustin (8), penicianstinoid A (9), and furanoaustinol (10), were isolated from the cultures of the algicolous fungus Penicillium sp. RR-DL-1-7, derived from the red alga Rhodomela confervoides. Their structures and relative configuration were established by detailed spectroscopic analysis of NMR and HR-MS experiments, and the absolute configurations were assigned by X-ray diffraction and ECD spectral analysis. None of the isolates showed obvious growth inhibitory effects against five plankton and four bacteria species tested.

3.
NPJ Precis Oncol ; 8(1): 153, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39033203

ABSTRACT

Racial/ethnic disparities mar NSCLC care and treatment outcomes. While socioeconomic factors and access to healthcare are important drivers of NSCLC disparities, a deeper understanding of genetic ancestry-associated genomic landscapes can better inform the biology and the treatment actionability for these tumors. We present a comprehensive ancestry-based prevalence and co-alteration landscape of genomic alterations and immunotherapy-associated biomarkers in patients with KRAS and EGFR-altered non-squamous (non-Sq) NSCLC. KRAS was the most frequently altered oncogene in European (EUR) and African (AFR), while EGFR alterations predominated in East Asian (EAS), South Asian (SAS), and Admixed American (AMR) groups, consistent with prior studies. As expected, STK11 and KEAP1 alterations co-occurred with KRAS alterations while showing mutual exclusivity with EGFR alterations. EAS and AMR KRAS-altered non-Sq NSCLC showed lower rates of co-occurring STK11 and KEAP1 alterations relative to other ancestry groups. Ancestry-specific co-alterations included the co-occurrence of KRAS and GNAS alterations in AMR, KRAS, and ARID1A alterations in SAS, and the mutual exclusivity of KRAS and NF1 alterations in the EUR and AFR ancestries. Contrastingly, EGFR-altered tumors exhibited a more conserved co-alteration landscape across ancestries. AFR exhibited the highest tumor mutational burden, with potential therapeutic implications for these tumors.

4.
Recent Pat Anticancer Drug Discov ; 19(4): 503-515, 2024.
Article in English | MEDLINE | ID: mdl-39044710

ABSTRACT

BACKGROUND: Both apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) inhibition and melatonin suppress prostate cancer (PCa) growth. OBJECTIVE: This study evaluated the therapeutic efficiency of self-assembled and prostate-specific membrane antigen (PSMA)-targeted nanocarrier loading 125I radioactive particles and encapsulating siRNA targeting APE1 (siAPE1) and melatonin for PCa. METHODS: The linear polyarginine R12 polypeptide was prepared using Fmoc-Arg-Pbf-OH. The PSMA-targeted polymer was synthesized by conjugating azide-modified R12 peptide to PSMA monoclonal antibody (mAb). Before experiments, the PSMA-R12 nanocarrier was installed with melatonin and siAPE1, which were subsequently labeled by 125I radioactive particles. In vitro biocompatibility and cytotoxicity of nanocomposites were examined in LNCaP cells and in vivo biodistribution and pharmacokinetics were determined using PCa tumor-bearing mice. RESULTS: PSMA-R12 nanocarrier was ~120 nm in size and was increased to ~150 nm by melatonin encapsulation. PSMA-R12 nanoparticles had efficient loading capacities of siAPE1, melatonin, and 125I particles. The co-delivery of melatonin and siAPE1 by PSMA-R12-125I showed synergistic effects on suppressing LNCaP cell proliferation and Bcl-2 expression and promoting cell apoptosis and caspase-3 expression. Pharmacokinetics analysis showed that Mel@PSMA-R12-125I particles had high uptake activity in the liver, spleen, kidney, intestine, and tumor, and were accumulated in the tumor sites within the first 8 h p.i., but was rapidly cleared from all the tested organs at 24 h p.i. Administration of nanoparticles to PCa tumors in vivo showed that Mel@PSMA-R12- 125I/siAPE1 had high efficiency in suppressing PCa tumor growth. CONCLUSION: The PSMA-targeted nanocarrier encapsulating siAPE1 and melatonin is a promising therapeutic strategy for PCa and can provide a theoretical basis for patent applications.


Subject(s)
Antigens, Surface , Glutamate Carboxypeptidase II , Iodine Radioisotopes , Melatonin , Nanoparticles , Prostatic Neoplasms , Male , Animals , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Humans , Iodine Radioisotopes/administration & dosage , Melatonin/pharmacology , Melatonin/administration & dosage , Cell Line, Tumor , Nanoparticles/chemistry , Mice , Glutamate Carboxypeptidase II/antagonists & inhibitors , Glutamate Carboxypeptidase II/metabolism , Tissue Distribution , Mice, Nude , Xenograft Model Antitumor Assays , Apoptosis/drug effects , Mice, Inbred BALB C , RNA, Small Interfering/administration & dosage , RNA, Small Interfering/pharmacology
5.
Huan Jing Ke Xue ; 45(7): 4052-4062, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022953

ABSTRACT

Microplastics are among the most difficult new pollutants to remove in wastewater treatment plants. In order to explore the occurrence form, size distribution, composition, removal efficiency, migration law, and fate behavior characteristics of microplastic particles in sewage plants, taking a sewage treatment plant in Hohhot as an example, a total of 17 sampling sites were set up. The LAS X software counted the shape, abundance, and size of microplastics and conducted a full-process analysis. The results showed that: fibrous microplastics had the highest abundance and widest distribution and were the main form of existence, accounting for 61.8% of the total abundance; the size of microplastics ranged mainly between 0 and 1.00 mm, and among the four sizes, the abundance of microplastics 0.25 to 0.50 mm in China was the highest, accounting for 32.9%. Among the eight types of plastic components detected, polyester substances (PET, PBT), cellulose, and polypropylene (PP) were the main components, accounting for 25%, 21%, and 17%, respectively. The influent abundance of the sewage plant was (73 ±5) n·L-1, the effluent abundance was (14 ±2) n·L-1, and the overall removal rate was (80.8 ±12.1)%. Among the three treatment stages of the sewage plant, only the primary treatment played a role in removal, and the abundance of microplastics surged in the secondary treatment. Different structures playing a major role in the removal of microplastics were fine grids (49.2 ±7.4)% and secondary sedimentation tanks (92.4 ±13.9)%. Microplastics mainly existed in the form of fibers, fragments, and films. The proportion of fibers was approximately 70%, and the size of fragments was mainly concentrated between 0.50 and 5.00 mm. Most fragments were in the range of 5.00 mm, accounting for 50%, making them the main form apart from fibrous. The film-like size was mostly concentrated in the range of less than 0.50 mm, accounting for more than 10%. Therefore, improving the removal of small-sized fibrous and film-like microplastics and large-sized fragmented microplastic particles can effectively reduce the pollution risk of microplastics in the environment caused by sewage plant drainage.


Subject(s)
Cities , Microplastics , Waste Disposal, Fluid , Wastewater , Water Pollutants, Chemical , Microplastics/analysis , Waste Disposal, Fluid/methods , Wastewater/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/isolation & purification , China , Sewage/chemistry , Plastics , Particle Size , Polypropylenes , Environmental Monitoring
6.
Sci Rep ; 14(1): 14055, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890445

ABSTRACT

To investigate the characteristics of destabilization damage in coal-rock complexes. Mechanical property tests were conducted on coal, rock, and their complexes. An infrared thermal camera was employed to real-time monitor the infrared (IR) radiation response signals during the destabilization damage process. A numerical model of coal-rock destabilization damage was developed, and its validity was verified. Deformed stress fields and displacement contours were obtained during the destabilization damage process. Upon destabilization, numerous cracks form at the base of the "coal" section, extending towards the interface, resulting in the formation of a wave-like deformation region. The differentiation in infrared thermal images is more pronounced in the "coal" section compared to the "rock" section. A high-stress region is evident at the interface, resulting in an area of high stress differentials. However, the bottom of the "coal" section also exhibits a region with high stress differentials and a more pronounced tendency towards destabilization damage. Displacement contours revealed that numerous units at the bottom of the "coal" section had slipped and misaligned, leading to the accumulation of damage and an elevation in the local damage level. It is a crucial factor contributing to the notable phenomenon of IR thermal image differentiation.

7.
Chem Commun (Camb) ; 60(53): 6793-6796, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38869018

ABSTRACT

We report an integrated ratiometric lysosomal nitric oxide (NO) nanoprobe based on engineered semiconducting polymer dots (Pdots), LyNO-Pdots, which consist of a newly designed NO-responsive dye, a fluorescent conjugated polymer and two functional polymers. The developed probe LyNO-Pdots exhibit high specificity and stability, good photostability and favorable blood-brain barrier (BBB) penetration ability. The LyNO-Pdots are successfully applied to ratiometric imaging of lysosomal NO variations in brain-derived endothelial cells, brain tissues and mice brains with Alzheimer's disease (AD). The results demonstrate that the NO content in the brains of AD mice is considerably higher than that in normal mice.


Subject(s)
Alzheimer Disease , Brain , Fluorescent Dyes , Lysosomes , Nitric Oxide , Optical Imaging , Animals , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/metabolism , Lysosomes/chemistry , Lysosomes/metabolism , Mice , Brain/diagnostic imaging , Brain/metabolism , Nitric Oxide/metabolism , Nitric Oxide/analysis , Fluorescent Dyes/chemistry , Fluorescent Dyes/chemical synthesis , Humans , Polymers/chemistry , Blood-Brain Barrier/metabolism , Quantum Dots/chemistry
8.
Nat Plants ; 10(6): 1027-1038, 2024 06.
Article in English | MEDLINE | ID: mdl-38831045

ABSTRACT

In bryophytes, sexual reproduction necessitates the release of motile sperm cells from a gametophyte into the environment. Since 1856, this process, particularly in liverworts, has been known to depend on water. However, the molecular mechanism underlying this phenomenon has remained elusive. Here we identify the plasma membrane protein MpMLO1 in Marchantia polymorpha, a model liverwort, as critical for sperm discharge from antheridia. The MpMLO1-expressing tip cells among the sperm-wrapping jacket cells undergo programmed cell death upon antheridium maturation to facilitate sperm discharge after the application of water and even hypertonic solutions. The absence of MpMLO1 leads to reduced cytoplasmic Ca2+ levels in tip cells, preventing cell death and consequently sperm discharge. Our findings reveal that MpMLO1-mediated programmed cell death in antheridial tip cells, regulated by cytosolic Ca2+ dynamics, is essential for sperm release, elucidating a key mechanism in bryophyte sexual reproduction and providing insights into terrestrial plant evolution.


Subject(s)
Marchantia , Plant Proteins , Marchantia/physiology , Marchantia/genetics , Marchantia/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Calcium/metabolism , Reproduction/physiology , Hepatophyta/physiology , Hepatophyta/metabolism , Hepatophyta/genetics , Apoptosis
9.
ACS Appl Mater Interfaces ; 16(23): 30284-30295, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38812067

ABSTRACT

As the power core of an electric vehicle, the performance of lithium-ion batteries (LIBs) is directly related to the vehicle quality and driving range. However, the charge-discharge performance and cycling performance are affected by the temperature. Excessive temperature can cause internal short circuits and even lead to safety issues, such as thermal runaway. The separator plays a crucial role in protecting the battery from regular operation, preventing direct touch between the cathode and the anode while allowing the transport of lithium ions. In this study, we have designed a thermoregulating separator in the shape of calabash, which uses melamine-encapsulated paraffin phase change material (PCM) with a wide enthalpy (0-168.52 J g-1) to dissipate the heat generated inside the battery promptly. Under extra-long-use conditions, the heat emitted by the battery is absorbed by the PCM without causing a significant temperature rise that triggers thermal runaway. The PCM separator can effectively suppress the temperature increase caused by battery penetration. Due to the unique structure of the PCM, the battery is short-circuited; it can significantly delay the internal temperature rise of the battery and quickly dissipate the heat, which is consistent with the characteristics of natural calabash in nutrient absorption and water diffusion, improving the melting and heat storage efficiency of the PCM. The design of the phase change separator provides an effective reference for overheat protection and improved safety in lithium-ion batteries.

10.
Clin Exp Rheumatol ; 2024 May 01.
Article in English | MEDLINE | ID: mdl-38757282

ABSTRACT

OBJECTIVES: To investigate whether the interplay of anti-galectin-3 antibodies (anti-Gal3 Abs) with neutrophils contributes to the development of lupus cutaneous vasculitis. METHODS: Enzyme-linked immunosorbent assay was used to determine the serum level of anti-Gal3 Abs in lupus patients. Flow cytometry, quantitative PCR and western blot were performed to investigate the expression of cell surface receptors, proinflammatory cytokines and signalling molecules in neutrophils stimulated by serum from lupus patients or healthy controls (HCs) or anti-Gal3 Ab, respectively. Immunofluorescence was performed to visualise the formation of neutrophil extracellular traps (NETs). Human umbilical vein endothelial cells were co-cultured with the supernatants from neutrophils stimulated by anti-Gal3 Ab, and cytokine production was measured at mRNA and protein levels. Immunohistochemistry was adopted to reveal the distribution of Gal3, cytokines and myeloperoxidase within lupus skin lesions. REULTS: Serum levels of anti-Gal3 Abs were negatively correlated with peripheral counts of neutrophils. Anti-Gal3 Abs positive sera from SLE patients accelerated neutrophil death, altered cell phenotype and promoted formation of NETs with the involvement of p38 MAPK pathway. Supernatants collected from neutrophils co-cultured with anti-Gal3 Ab provoked endothelial cells to produce cytokines such as IL-1, ICAM-1, SELE and particularly IL-6. Consistently, IL-6 was higher in SLE patients with anti-Gal3 Ab positive sera and enriched in the area of vascular inflammation together with enhanced expression of Gal3 protein and infiltration of neutrophils. CONCLUSIONS: Overall, these findings suggested that neutrophils were crucial mediators in anti-Gal3 Ab induced lupus cutaneous vasculitis.

12.
BMC Urol ; 24(1): 111, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778291

ABSTRACT

BACKGROUND: Patients with spinal cord injury have a relatively high risk for bladder cancer and often complicated with bladder cancer in advanced stages, and the degree of aggressiveness of malignancy is high. Most of the literature is based on disease clinical features while, our study reviews the clinical characteristics and molecular mechanisms of spinal cord injury patients with bladder cancer, so that it might help clinicians better recognize and manage these patients. METHOD: We searched PubMed, Web of Science and Embase, using retrieval type like ("Neurogenic Lower Urinary Tract Dysfunction" OR "Spinal cord injury" OR "Spinal Cord Trauma") AND ("bladder cancer" OR "bladder neoplasm" OR "bladder carcinoma" OR "Urinary Bladder Neoplasms" OR "Bladder Tumor"). In Web of Science, the retrieval type was searched as "Topic", and in PubMed and Embase, as "All Field". The methodological quality of eligible studies and their risk of bias were assessed using the Newcastle-Ottawa scale. This article is registered in PROSPERO with the CBD number: CRD42024508514. RESULT: In WOS, we searched 219 related papers, in PubMed, 122 and in Embase, 363. Thus, a total of 254 articles were included after passing the screening, within a time range between 1960 and 2023. A comprehensive analysis of the data showed that the mortality and incidence rates of bladder cancer in spinal cord injury patients were higher than that of the general population, and the most frequent pathological type was squamous cell carcinoma. In parallel to long-term urinary tract infection and indwelling catheterization, the role of molecules such as NO, MiR 1949 and Rb 1. was found to be crucial pathogenetically. CONCLUSION: This review highlights the risk of bladder cancer in SCI patients, comprehensively addressing the clinical characteristics and related molecular mechanisms. However, given that there are few studies on the molecular mechanisms of bladder cancer in spinal cord injury, further research is needed to expand the understanding of the disease.


Subject(s)
Spinal Cord Injuries , Urinary Bladder Neoplasms , Spinal Cord Injuries/complications , Humans , Urinary Bladder Neoplasms/complications
13.
Heliyon ; 10(10): e31403, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38803848

ABSTRACT

The main component of O-glycoproteins, mucin, is known to play important roles in physiological conditions and oncogenic processes, particularly correlated with poor prognosis in different carcinomas. Diffuse-type gastric cancer (DGC) has long been associated with genomic stability and unfavorable clinical outcomes. To investigate further, we obtained clinical information and the RNA-seq data of the TCGA-STAD cohort. Through the use of unsupervised clustering methods and GSEA, we identified two distinct clusters, characterized by higher and lower expression of MUC2 and MUC20, denoted as cluster 1 and cluster 2, respectively. Subsequently, employing CIBERSORT, it was determined that cluster 2 exhibited a higher tumor mutation burden (TMB) and a greater abundance of CD8+ T cells and activated CD4+ memory T cells, in addition to immune checkpoints (ICPs). On the other hand, cluster 1 showed a lower TIDE score estimation, indicating a higher probability of tumor immune escape. Furthermore, overexpression of MUC15 and MUC20 was confirmed through qPCR and Western blotting, and their specific roles in mediating the epithelial-mesenchymal transition (EMT) process of GC cells (SNU484 and Hs746t) were validated via CCK-8 assay and wound healing assay in vitro. These findings highlight the potential prognostic value of MUC20 and offer insights into the prospects of immunotherapy for DGC by targeting MUC20.

14.
World Neurosurg ; 187: e129-e135, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38621501

ABSTRACT

PURPOSE: This study aims to observe the safety and effectiveness of 10-mm endoscopic minimally invasive interlaminar decompression in the treatment of ossified lumbar spinal stenosis. METHODS: The clinical data of 50 consecutive patients with ossified lumbar spinal stenosis were retrospectively analyzed. All patients underwent minimally invasive interlaminar decompression with 10-mm endoscope. Patient demographics, perioperative data, and clinical outcomes were recorded. Visual analog scale scores, Oswestry disability index scores, and modified Macnab criteria were used to assess clinical outcomes. The lateral recess angle, real spinal canal area, and effective intervertebral foramen area were used to assess the effect of decompression. RESULTS: The mean age of all patients was 59.0 ± 12.3 years. The mean operative time and intraoperative blood loss were 43.7 ± 8.7 minutes and <20 ml, respectively. Two years after surgery, the leg pain Visual analog scale score decreased from 7.4 ± 1.0 to 1.6 ± 0.6 (P < 0.05) and the Oswestry disability index score decreased from 63.8 ± 7.6 to 21.7 ± 3.4 (P < 0.05). The lateral recess angle, real spinal canal area and effective intervertebral foramen area were significantly larger than before surgery (P < 0.05). The overall excellent and good rate at the last follow-up was 92.0% according to the modified Macnab criteria. CONCLUSIONS: The 10-mm endoscopic minimally invasive interlaminar decompression can safely and effectively remove the ossification in the spinal canal and achieve adequate decompression in patients with ossified lumbar spinal stenosis.


Subject(s)
Decompression, Surgical , Lumbar Vertebrae , Minimally Invasive Surgical Procedures , Spinal Stenosis , Humans , Spinal Stenosis/surgery , Spinal Stenosis/diagnostic imaging , Middle Aged , Female , Decompression, Surgical/methods , Male , Lumbar Vertebrae/surgery , Aged , Retrospective Studies , Treatment Outcome , Minimally Invasive Surgical Procedures/methods , Neuroendoscopy/methods , Ossification, Heterotopic/surgery , Endoscopy/methods , Adult
15.
Bioorg Chem ; 147: 107400, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38688196

ABSTRACT

Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers.This reviewcomprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy.


Subject(s)
Neoplasms , Ubiquitin Thiolesterase , Humans , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Ubiquitin Thiolesterase/antagonists & inhibitors , Ubiquitin Thiolesterase/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Animals , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Molecular Structure
16.
BioDrugs ; 38(3): 353-367, 2024 May.
Article in English | MEDLINE | ID: mdl-38520608

ABSTRACT

Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.


Subject(s)
Erectile Dysfunction , Stem Cell Transplantation , Humans , Erectile Dysfunction/therapy , Male , Stem Cell Transplantation/methods , Animals , Stem Cells
17.
Chin J Integr Med ; 30(6): 543-550, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38532151

ABSTRACT

OBJECTIVE: To observe the angiogenesis effect of electroacupuncture (EA) at Shuigou acupoint (GV 26) in the treatment of cerebral ischemia, and explore the value of miRNA-7 (miR-7) in it. METHODS: First, 48 mice were randomly divided into sham operation, middle cerebral artery occlusion (MCAO) model, and EA treatment groups. Then 9 mice were divided into carrier control group, miR-7 knockout group and miR-7 overexpression group (n=3 each group). Finally, 20 mice were divided into model and carrier control group, model and miR-7 knockout group, EA treatment and carrier control group and EA treatment and miR-7 overexpression group, with 3-6 mice in each group. The MCAO model was established in the MCAO and EA groups. Neurological deficit score and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the severity of cerebral ischemia. Hematoxylin-eosin staining was used to describe basic pathological changes. Immunohistochemistry was used to quantify cerebral microvessel density. Real-time PCR and Western blot were used to detect the expression of miR-7 and its downstream target genes Krüppel-like factor 4/vascular endothelial growth factor (KLF4/VEGF) and angiopoietin-2 (ANG-2) in the ischemic cerebral cortex. RESULTS: After EA, neurological deficit scores and infarction volumes decreased, and the density of cerebral microvessels increased. In the MCAO group, miR-7 expression was higher than that in the sham group (P<0.01). After EA at GV 26, miR-7 expression decreased (P<0.01) and the expression of downstream target genes KLF4/VEGF and ANG-2 increased as compared with the MCAO group (P<0.01). After EA combined with overexpression of miR-7, the expression of downstream target genes KLF4/VEGF and ANG-2 decreased compared to the control EA group (P<0.01). After miR-7 knockdown, the expression of KLF4/VEGF and ANG-2 increased (P<0.05 or P<0.01). CONCLUSIONS: EA could promote angiogenesis in MCAO mice likely by inhibiting the expression of miR-7 and relieving inhibition of downstream target genes KLF4/VEGF and ANG-2.


Subject(s)
Brain Ischemia , Electroacupuncture , Kruppel-Like Factor 4 , MicroRNAs , Neovascularization, Physiologic , Animals , MicroRNAs/genetics , MicroRNAs/metabolism , Neovascularization, Physiologic/genetics , Male , Brain Ischemia/therapy , Brain Ischemia/genetics , Brain Ischemia/pathology , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Mice , Kruppel-Like Transcription Factors/metabolism , Kruppel-Like Transcription Factors/genetics , Mice, Inbred C57BL , Infarction, Middle Cerebral Artery/therapy , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/genetics , Microvessels/pathology , Disease Models, Animal , Angiogenesis
18.
World J Gastroenterol ; 30(8): 943-955, 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38516249

ABSTRACT

BACKGROUND: Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery. AIM: To summarize and analyze current research results on QOL after pancreatic surgery. METHODS: A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively. RESULTS: A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear. CONCLUSION: The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

20.
World J Gastrointest Oncol ; 16(2): 343-353, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38425394

ABSTRACT

BACKGROUND: The controlling nutritional status (CONUT) score effectively reflects a patient's nutritional status, which is closely related to cancer prognosis. This study investigated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer, and compared the predictive ability of the CONUT score with other indexes. AIM: To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative resection. METHODS: This retrospective analysis included 217 patients with newly diagnosed colorectal. The CONUT score was calculated based on the serum albumin level, total lymphocyte count, and total cholesterol level. The cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic curve. The associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression analysis. RESULTS: Using the cutoff value of the CONUT score, patients were stratified into CONUT low (n = 189) and CONUT high groups (n = 28). The CONUT high group had worse overall survival (OS) (P = 0.013) and relapse-free survival (RFS) (P = 0.015). The predictive performance of CONUT was superior to the modified Glasgow prognostic score, the prognostic nutritional index, and the neutrophil-to-lymphocyte ratio. Meanwhile, the predictive performances of CONUT + tumor node metastasis (TNM) stage for 3-year OS [area under the receiver operating characteristics curve (AUC) = 0.803] and 3-year RFS (AUC = 0.752) were no less than skeletal muscle mass index (SMI) + TNM stage. The CONUT score was negatively correlated with SMI (P < 0.01). CONCLUSION: As a nutritional indicator, the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer, and its predictive ability was superior to other indexes. The correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

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