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Journal of Radiation Research May 2024Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context,...
Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro, and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1β and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic.
Topics: Animals; NF-E2-Related Factor 2; Humans; Hepatocyte Growth Factor; Wound Healing; Plasmids; Skin; Mice; Signal Transduction; Radiation Injuries; Apoptosis; Cell Survival; Cytokines; HaCaT Cells; Male; Keratinocytes
PubMed: 38682896
DOI: 10.1093/jrr/rrae011 -
Asian Pacific Journal of Cancer... Apr 2024Cervical cancer, globally, ranks as the runner-up among the most prevalent forms of cancer affecting women. The role of the tumor necrosis factor alpha (TNF-α)... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cervical cancer, globally, ranks as the runner-up among the most prevalent forms of cancer affecting women. The role of the tumor necrosis factor alpha (TNF-α) polymorphism in the susceptibility to cervical cancer has been a subject of interest. However, the current evidence regarding this association remains inconclusive.
METHODS
To address this uncertainty, eligible studies were systematically searched and retrieved from various databases including Cochrane Library, EMBASE, PubMed, Web of Science, CNKI, and Wanfang database. The search was conducted until September 01, 2023. The collected literature was then subjected to independent analysis by two authors. The pooled odds ratio along with the corresponding 95% confidence interval was calculated using different genetic models. Additionally, sensitivity and cumulative analyses were performed to assess the stability of the obtained results.
RESULTS
A total of 29 case-control studies involving 8850 cases and 9286 controls were included in the present analysis. The findings revealed that the TNF-α rs1800629 polymorphism increased the risk of cervical cancer under the allele genetic model (A vs. G: OR = 1.277, 95% CI = 1.104-1.477, P = 0.001) in the general population. Subgroup analysis based on ethnicity demonstrated that this polymorphism was associated with an increased risk of cervical cancer in Caucasian and African women, but not in Asians. Furthermore, subgroup analysis based on country of origin indicated a significant correlation between the TNF-α rs1800629 polymorphism and an increased risk of cervical cancer in American and Chinese women, but not in Iranian women.
CONCLUSIONS
The findings from this meta-analysis suggest that the TNF-α rs1800629 polymorphism is a risk factor for cervical cancer in the general population, particularly in Caucasian and African women. However, further well-designed studies are warranted to validate these findings.
Topics: Humans; Uterine Cervical Neoplasms; Female; Tumor Necrosis Factor-alpha; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Case-Control Studies; Risk Factors; Prognosis
PubMed: 38679974
DOI: 10.31557/APJCP.2024.25.4.1155 -
Brain Sciences Mar 2024Differentiating recurrent cerebral metastasis (CM) from brain radiation necrosis (BRN) is pivotal for guiding appropriate treatment and prognostication. Despite advances...
Differentiating recurrent cerebral metastasis (CM) from brain radiation necrosis (BRN) is pivotal for guiding appropriate treatment and prognostication. Despite advances in imaging techniques, however, accurately distinguishing these conditions non-invasively is still challenging. This single-center retrospective study reviewed 32 cases (28 patients) with confirmed cerebral metastases who underwent surgical excision of lesions initially diagnosed by MRI and/or MR perfusion scans from 1 January 2015 to 30 September 2020. Diagnostic accuracy was assessed by comparing imaging findings with postoperative histopathology. Conventional MRI accurately identified recurrent CM in 75% of cases. MR perfusion scans showed significantly higher mean maximum relative cerebral blood volume (max. rCBV) in metastasis cases, indicating its potential as a discriminative biomarker. No single imaging modality could definitively distinguish CM from BRN. Survival analysis revealed gender as the only significant factor affecting overall survival, with no significant survival difference observed between patients with CM and BRN after controlling for confounding factors. This study underscores the limitations of both conventional MRI and MR perfusion scans in differentiating recurrent CM from BRN. Histopathological examination remains essential for accurate diagnosis. Further research is needed to improve the reliability of non-invasive imaging and to guide the management of patients with these post-radiation events.
PubMed: 38671973
DOI: 10.3390/brainsci14040321 -
International Journal of Molecular... Jun 2024Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co‑receptor β‑klotho...
Ultrasound‑targeted microbubble destruction technology delivering β‑klotho to the heart enhances FGF21 sensitivity and attenuates heart remodeling post‑myocardial infarction.
Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co‑receptor β‑klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the gene via ultrasound‑targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post‑acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post‑infarction were determined using ELISA. Sprague‑Dawley rats received the 3X UTMD‑mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post‑infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α‑klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post‑infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. , the UTMD technology‑mediated delivery of KLB@CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2‑related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post‑myocardial infarction.
Topics: Fibroblast Growth Factors; Animals; Microbubbles; Myocardial Infarction; Klotho Proteins; Rats, Sprague-Dawley; Humans; Male; Rats; Ventricular Remodeling; Female; Ultrasonic Waves; Myocardium; Heart Failure
PubMed: 38666537
DOI: 10.3892/ijmm.2024.5378 -
Acute ST-Elevation Myocardial Infarction in a Young Adult: Rare Presentation of Giant Atrial Myxoma.Arquivos Brasileiros de Cardiologia 2024Cardiac tumors are rare entities, among which atrial myxoma (AM) stands as the most frequent, accounting for approximately half of all reported cases. The incidence of...
Cardiac tumors are rare entities, among which atrial myxoma (AM) stands as the most frequent, accounting for approximately half of all reported cases. The incidence of AM is estimated to range from 0.001% to 0.3% within the general population, yet only about 0.06% of these cases present with coronary embolic events. We report on a 33-year-old male smoker who experienced acute, severe precordial pain radiating to the left upper limb, lasting for one hour. The electrocardiographic evaluation demonstrated ST-segment elevation in leads D2, D3, and aVF, alongside significantly elevated serum troponin levels, confirming a diagnosis of ST-segment elevation myocardial infarction (STEMI). Subsequent coronary angiography revealed proximal occlusion of the right coronary artery due to thrombus. An initial attempt of thrombus aspiration was unsuccessful, followed by primary angioplasty with balloon inflation without stent placement. Further diagnostic exploration through transthoracic echocardiography identified a homogenous, smooth-surfaced mass measuring 5.2 cm x 2.3 cm attached to the interatrial septum. This mass, characterized by lobulations, prolapsed into the mitral valve and left ventricle during diastole, consistent with AM. Surgical resection of the mass was successfully performed, with the patient being discharged asymptomatic. In the reported case, the patient's profile, notably his age, and gender, diverges from the typical epidemiological characteristics associated with AM. This case adds to the limited number of reports where the inferior wall is affected by the right coronary artery being occluded. This report emphasizes the significance of differential diagnoses in younger patients presenting with STEMI.
Topics: Humans; Male; Adult; Myxoma; Heart Neoplasms; ST Elevation Myocardial Infarction; Heart Atria; Echocardiography; Electrocardiography; Coronary Angiography
PubMed: 38655985
DOI: 10.36660/abc.20230538 -
Communications Biology Apr 2024Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is...
Bile infarct is a pivotal characteristic of obstructive biliary disease, but its evolution during the disease progression remains unclear. Our objective, therefore, is to explore morphological alterations of the bile infarct in the disease course by means of multiscale X-ray phase-contrast CT. Bile duct ligation is performed in mice to mimic the obstructive biliary disease. Intact liver lobes of the mice are scanned by phase-contrast CT at various resolution scales. Phase-contrast CT clearly presents three-dimensional (3D) images of the bile infarcts down to the submicron level with good correlation with histological images. The CT data illustrates that the infarct first appears on day 1 post-BDL, while a microchannel between the infarct and hepatic sinusoids is identified, the number of which increases with the disease progression. A 3D model of hepatic acinus is proposed, in which the infarct starts around the portal veins (zone I) and gradually progresses towards the central veins (zone III) during the disease process. Multiscale phase-contrast CT offers the comprehensive analysis of the evolutionary features of the bile infarct in obstructive biliary disease. During the course of the disease, the bile infarcts develop infarct-sinusoidal microchannels and gradually occupy the whole liver, promoting the disease progression.
Topics: Animals; Mice; Tomography, X-Ray Computed; Cholestasis; Bile Ducts; Disease Progression; Male; Liver; Disease Models, Animal; Mice, Inbred C57BL; Imaging, Three-Dimensional; Infarction
PubMed: 38654111
DOI: 10.1038/s42003-024-06185-7 -
Journal of Hazardous Materials Jun 2024Micro- and nanoplastics (MNPs) are ubiquitous in the environment, resulting in the uptake of MNPs by a variety of organisms, including humans, leading to particle-cell...
Micro- and nanoplastics (MNPs) are ubiquitous in the environment, resulting in the uptake of MNPs by a variety of organisms, including humans, leading to particle-cell interaction. Human macrophages derived from THP-1 cell lines take up Polystyrene (PS), a widespread plastic. The question therefore arises whether primary human macrophages also take up PS micro- and nanobeads (MNBs) and how they react to this stimulation. Major aim of this study is to visualize this uptake and to validate the isolation of macrophages from peripheral blood mononuclear cells (PBMCs) to assess the impact of MNPs on human macrophages. Uptake of macrophages from THP-1 cell lines and PBMCs was examined by transmission electron microscopy (TEM), scanning electron microscopy and live cell imaging. In addition, the reaction of the macrophages was analyzed in terms of metabolic activity, cytotoxicity, production of reactive oxygen species (ROS) and macrophage polarization. This study is the first to visualize PS MNBs in primary human cells using TEM and live cell imaging. Metabolic activity was size- and concentration-dependent, necrosis and ROS were increased. The methods demonstrated in this study outline an approach to assess the influence of MNP exposure on human macrophages and help investigating the consequences of worldwide plastic pollution.
Topics: Humans; Macrophages; Reactive Oxygen Species; Polystyrenes; THP-1 Cells; Microplastics; Leukocytes, Mononuclear; Nanoparticles; Cell Survival; Microscopy, Electron, Transmission; Particle Size
PubMed: 38642497
DOI: 10.1016/j.jhazmat.2024.134253 -
Hybrid bio-nanoporous peptide loaded-polymer platforms with anticancer and antibacterial activities.Nanoscale Advances Apr 2024In this study, hybrid bio-nanoporous peptides loaded onto poly(-isopropylacrylamide--butylacrylate) (pNIPAM--BA) coatings were designed and obtained matrix-assisted...
In this study, hybrid bio-nanoporous peptides loaded onto poly(-isopropylacrylamide--butylacrylate) (pNIPAM--BA) coatings were designed and obtained matrix-assisted pulsed laser evaporation (MAPLE) technique. The incorporation of cationic peptides magainin (MG) and melittin (Mel) and their combination was tailored to target synergistic anticancer and antibacterial activities with low toxicity on normal mammalian cells. Atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy as well as contact angle and surface energy measurements revealed the successful and functional incorporation of both the peptides within porous polymeric nanolayers as well as surface modifications ( variation in the pore size diameter, surface roughness, and wettability) after Mel, MG or Mel-MG incorporation compared to pNIPAM--BA. testing revealed the impairment of biofilm formation on all the hybrid coatings while testing with , and . Moreover, MG was shown to modulate the effect of Mel in the combined Mel-MG extract formulation released pNIPAM-platforms, thus significantly reducing cancer cell proliferation through apoptosis/necrosis as revealed by flow cytometry analysis performed on HEK293T, A375, B16F1 and B16F10 cells. To the best of our knowledge, Mel-MG combination entrapped in the pNIPAM--BA copolymer has not yet been reported as a new promising candidate with anticancer and antibacterial properties for improved utility in the biomedical field. Mel-MG incorporation compared to pNIPAM--BA in testing revealed the impairment of biofilm formation in all the hybrid formulations.
PubMed: 38633049
DOI: 10.1039/d3na00947e -
IScience Apr 2024Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain...
Stereotactic radiosurgery (SRS) has been shown to be efficacious for the treatment of limited brain metastasis (BM); however, the effects of SRS on human brain metastases have yet to be studied. We performed genomic analysis on resected brain metastases from patients whose resected lesion was previously treated with SRS. Our analyses demonstrated for the first time that patients possess a distinct genomic signature based on type of treatment failure including local failure, leptomeningeal spread, and radio-necrosis. Examination of the center and peripheral edge of the tumors treated with SRS indicated differential DNA damage distribution and an enrichment for tumor suppressor mutations and DNA damage repair pathways along the peripheral edge. Furthermore, the two clinical modalities used to deliver SRS, LINAC and GK, demonstrated differential effects on the tumor landscape even between controlled primary sites. Our study provides, in human, biological evidence of differential effects of SRS across BM's.
PubMed: 38623341
DOI: 10.1016/j.isci.2024.109601 -
Journal of Neuro-oncology May 2024Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and... (Meta-Analysis)
Meta-Analysis Comparative Study Review
PURPOSE
Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms.
METHODS
PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes.
RESULTS
Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT).
CONCLUSION
Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.
Topics: Humans; Bevacizumab; Radiation Injuries; Necrosis; Laser Therapy; Central Nervous System Neoplasms; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors
PubMed: 38619777
DOI: 10.1007/s11060-024-04650-1