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Biomedical Engineering Online Jun 2024Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric...
BACKGROUND
Metastasis is one of the main factors leading to the high mortality rate of gastric cancer. The current monitoring methods are not able to accurately monitor gastric cancer metastasis.
METHODS
In this paper, we constructed a new type of hollow nanocomposites, @HMSN-Cy7.5-FA, which had a size distribution of approximately 100 nm and showed good stability in different liquid environments. The in vitro magnetic resonance imaging (MRI) results show that the nanocomposite has good response effects to the acidic microenvironment of tumors. The acidic environment can significantly enhance the contrast of -weighted MRI. The cellular uptake and endocytosis results show that the nanocomposite has good targeting capabilities and exhibits good biosafety, both in vivo and in vitro. In a gastric cancer nude mouse orthotopic metastatic tumor model, with bioluminescence imaging's tumor location information, we realized in vivo MRI/fluorescence imaging (FLI) guided precise monitoring of the gastric cancer orthotopic and metastatic tumors with this nanocomposite.
RESULTS
This report demonstrates that @HMSN-Cy7.5-FA nanocomposites is a promising nano-diagnostic platform for the precision diagnosis and therapy of gastric cancer metastasis in the future.
CONCLUSIONS
In vivo MRI/FLI imaging results show that the nanocomposites can achieve accurate monitoring of gastric cancer tumors in situ and metastases. BLI's tumor location information further supports the good accuracy of MRI/FLI dual-modality imaging. The above results show that the MHCF NPs can serve as a good nano-diagnostic platform for precise in vivo monitoring of tumor metastasis. This nanocomposite provides more possibilities for the diagnosis and therapy of gastric cancer metastases.
Topics: Stomach Neoplasms; Animals; Nanocomposites; Magnetic Resonance Imaging; Mice; Cell Line, Tumor; Neoplasm Metastasis; Humans; Folic Acid; Manganese Compounds; Optical Imaging; Mice, Nude; Oxides
PubMed: 38858706
DOI: 10.1186/s12938-024-01248-6 -
Carbohydrate Polymers Sep 2024This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), β-cyclodextrin (β-CD), and magnetic graphene oxide...
This article presents a novel approach to treating prostate cancer using a nanocarrier composed of folic acid (FA), β-cyclodextrin (β-CD), and magnetic graphene oxide (MGO) as a theranostic agent. The carrier is designed to improve the solubility and bioavailability of curcumin, a potential therapeutic substance against prostate cancer. Folic acid receptors overexpressed on the surface of solid tumors, including prostate cancer, may facilitate targeted drug delivery to tumor cells while avoiding nonspecific effects on healthy tissues. The anticancer efficacy of Folic acid-curcumin@β-CD-MGO in vitro was also examined on LNCaP (an androgen-dependent) and PC3 (an androgen-independent) prostate cancer cells. The relaxivity of nanoparticles in MRI images was also investigated as a diagnostic factor. The results showed a concentration-dependent inhibitory effect on cell proliferation, induction of oxidative damage, and apoptotic effects. Also, nanoparticle relaxometry shows that this agent can be used as a negative contrast agent in MRI images. Overall, this study represents a promising theranostic agent to improve the delivery and trace of curcumin and enhance its therapeutic potential in the treatment of prostate cancer.
Topics: Curcumin; Male; Graphite; Humans; Prostatic Neoplasms; beta-Cyclodextrins; Theranostic Nanomedicine; Folic Acid; Cell Proliferation; Apoptosis; Cell Line, Tumor; Antineoplastic Agents; Drug Carriers; Magnetic Resonance Imaging; Nanoparticles; Folate Receptors, GPI-Anchored; Drug Liberation; Magnetite Nanoparticles
PubMed: 38857995
DOI: 10.1016/j.carbpol.2024.122328 -
FASEB Journal : Official Publication of... Jun 2024Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs)....
Maternal nutrition contributes to gene-environment interactions that influence susceptibility to common congenital anomalies such as neural tube defects (NTDs). Supplemental myo-inositol (MI) can prevent NTDs in some mouse models and shows potential for prevention of human NTDs. We investigated effects of maternal MI intake on embryonic MI status and metabolism in curly tail mice, which are genetically predisposed to NTDs that are inositol-responsive but folic acid resistant. Dietary MI deficiency caused diminished MI in maternal plasma and embryos, showing that de novo synthesis is insufficient to maintain MI levels in either adult or embryonic mice. Under normal maternal dietary conditions, curly tail embryos that developed cranial NTDs had significantly lower MI content than unaffected embryos, revealing an association between diminished MI status and failure of cranial neurulation. Expression of inositol-3-phosphate synthase 1, required for inositol biosynthesis, was less abundant in the cranial neural tube than at other axial levels. Supplemental MI or d-chiro-inositol (DCI) have previously been found to prevent NTDs in curly tail embryos. Here, we investigated the metabolic effects of MI and DCI treatments by mass spectrometry-based metabolome analysis. Among inositol-responsive metabolites, we noted a disproportionate effect on nucleotides, especially purines. We also found altered proportions of 5-methyltetrahydrolate and tetrahydrofolate in MI-treated embryos suggesting altered folate metabolism. Treatment with nucleotides or the one-carbon donor formate has also been found to prevent NTDs in curly tail embryos. Together, these findings suggest that the protective effect of inositol may be mediated through the enhanced supply of nucleotides during neural tube closure.
Topics: Inositol; Neural Tube Defects; Animals; Female; Mice; Pregnancy; Embryo, Mammalian; Maternal Nutritional Physiological Phenomena; Metabolome; Folic Acid
PubMed: 38855924
DOI: 10.1096/fj.202400206R -
JCI Insight Jun 2024TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac...
TANGO2-deficiency disorder (TDD) is an autosomal-recessive genetic disease caused by biallelic loss-of-function variants in the TANGO2 gene. TDD-associated cardiac arrhythmias are recalcitrant to standard antiarrhythmic medications and constitute the leading cause of death. Disease modeling for TDD has been primarily carried out using human dermal fibroblast and, more recently, in Drosophila by multiple research groups. No human cardiomyocyte system has been reported, which greatly hinders the investigation and understanding of TDD-associated arrhythmias. Here, we established potentially novel patient-derived induced pluripotent stem cell differentiated cardiomyocyte (iPSC-CM) models that recapitulate key electrophysiological abnormalities in TDD. These electrophysiological abnormalities were rescued in iPSC-CMs with either adenoviral expression of WT-TANGO2 or correction of the pathogenic variant using CRISPR editing. Our natural history study in patients with TDD suggests that the intake of multivitamin/B complex greatly diminished the risk of cardiac crises in patients with TDD. In agreement with the clinical findings, we demonstrated that high-dose folate (vitamin B9) virtually abolishes arrhythmias in TDD iPSC-CMs and that folate's effect was blocked by the dihydrofolate reductase inhibitor methotrexate, supporting the need for intracellular folate to mediate antiarrhythmic effects. In summary, data from TDD iPSC-CM models together with clinical observations support the use of B vitamins to mitigate cardiac crises in patients with TDD, providing potentially life-saving treatment strategies during life-threatening events.
Topics: Humans; Induced Pluripotent Stem Cells; Myocytes, Cardiac; Folic Acid; Arrhythmias, Cardiac; Male; Female; Child
PubMed: 38855866
DOI: 10.1172/jci.insight.171005 -
International Journal of Nanomedicine 2024This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular...
PURPOSE
This study aimed to construct targeting drug-loading nanocomposites (FA-FePt/DDP nanoliposomes) to explore their potential in ovarian cancer therapy and molecular magnetic resonance imaging (MMRI).
METHODS
FA-FePt-NPs were prepared by coupling folate (FA) with polyethylene-glycol (PEG)-coated ferroplatinum nanoparticles and characterized. Then cisplatin (DDP) was encapsulated in FA-FePt-NPs to synthesize FA-PEG-FePt/DDP nanoliposomes by thin film-ultrasonic method and high-speed stirring, of which MMRI potential, magnetothermal effect, and the other involved performance were analyzed. The therapeutic effect of FA-FePt/DDP nanoliposomes combined with magnetic fluid hyperthermia (MFH) on ovarian cancer in vitro and in vivo was evaluated. The expression levels of Bax and epithelial-mesenchymal transition related proteins were detected. The biosafety was also preliminarily observed.
RESULTS
The average diameter of FA-FePt-NPs was about 30 nm, FA-FePt/DDP nanoliposomes were about 70 nm in hydrated particle size, with drug slow-release and good cell-specific targeted uptake. In an alternating magnetic field (AMF), FA-FePt/DDP nanoliposomes could rapidly reach the ideal tumor hyperthermia temperature (42~44 °C). MRI scan showed that FA-FePt-NPs and FA-FePt/DDP nanoliposomes both could suppress the T2 signal, indicating a good potential for MMRI. The in vitro and in vivo experiments showed that FA-FePt/DDP-NPs in AMF could effectively inhibit the growth of ovarian cancer by inhibiting cancer cell proliferation, invasion, and migration, and inducing cancer cell apoptosis, much better than that of the other individual therapies; molecularly, E-cadherin and Bax proteins in ovarian cancer cells and tissues were significantly increased, while N-cadherin, Vimentin, and Bcl-2 proteins were inhibited, effectively inhibiting the malignant progression of ovarian cancer. In addition, no significant pathological injury and dysfunction was observed in major visceras.
CONCLUSION
We successfully synthesized FA-FePt/DDP nanoliposomes and confirmed their good thermochemotherapeutic effect in AMF and MMRI potential on ovarian cancer, with no obvious side effects, providing a favorable strategy of integrated targeting therapy and diagnosis for ovarian cancer.
Topics: Female; Ovarian Neoplasms; Liposomes; Cisplatin; Animals; Folic Acid; Humans; Magnetic Resonance Imaging; Polyethylene Glycols; Cell Line, Tumor; Antineoplastic Agents; Mice; Platinum; Hyperthermia, Induced; Nanocomposites; Mice, Nude; Mice, Inbred BALB C; Metal Nanoparticles; Magnetic Fields; Particle Size
PubMed: 38855734
DOI: 10.2147/IJN.S453601 -
Turkish Journal of Ophthalmology Jun 2024To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE).
OBJECTIVES
To investigate the clinical efficacy and safety of the modified Cretan protocol in patients with post-laser in situ keratomileusis ectasia (PLE).
MATERIALS AND METHODS
In this retrospective study, 26 eyes of 16 patients with PLE were treated with the modified Cretan protocol (combined transepithelial phototherapeutic keratectomy and accelerated corneal collagen cross-linking). Visual, refractive, tomographic, and aberrometric outcomes and point spread function (PSF) were recorded preoperatively and at 6, 12, and 24 months after treatment.
RESULTS
Both uncorrected and best corrected visual acuity were stable at 24 months postoperatively compared to baseline (from 0.89±0.36 to 0.79±0.33 logarithm of the minimum angle of resolution [LogMAR] and 0.31±0.25 to 0.24±0.19 LogMAR, respectively, p>0.05 for all values). The mean K1, K2, Kmean, thinnest corneal thickness, and spherical aberration at baseline were 45.76±5.75 diopters (D), 48.62±6.17 D, 47.13±5.89 D, 433.16±56.86 μm, and -0.21±0.63 μm respectively. These values were reduced to 42.86±6.34 D, 45.92±6.74 D, 44.21±6.4 D, 391.07±54.76 μm, and -0.51±0.58 μm at 24 months postoperatively (p<0.001, p=0.002, p<0.001, p=0.001, and p=0.02, respectively). The mean spherical equivalent, manifest cylinder, Kmax, central corneal thickness, other corneal aberrations (root mean square, trefoil, coma, quatrefoil, astigmatism), and PSF remained stable (p>0.05 for all variables), while anterior and posterior elevation were significantly improved at 24 months postoperatively (p<0.001 and p=0.02, respectively). No surgical complications occurred during the 24-month follow-up.
CONCLUSION
The modified Cretan protocol is a safe and effective treatment option for PLE patients that provides visual stabilization and significant improvement in topographic parameters during the 24-month follow-up. Further studies are needed to support our results.
Topics: Humans; Retrospective Studies; Keratomileusis, Laser In Situ; Male; Female; Visual Acuity; Adult; Dilatation, Pathologic; Corneal Topography; Refraction, Ocular; Cross-Linking Reagents; Treatment Outcome; Photosensitizing Agents; Young Adult; Collagen; Lasers, Excimer; Follow-Up Studies; Riboflavin; Photochemotherapy; Corneal Diseases; Cornea; Postoperative Complications; Myopia; Ultraviolet Rays
PubMed: 38853628
DOI: 10.4274/tjo.galenos.2024.82342 -
Annals of Saudi Medicine 2024Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to...
BACKGROUND
Medical treatment, expectant approaches, and surgical treatment options are available in the treatment of ectopic pregnancy. Regardless of the treatment, in addition to its effectiveness, the main concern is to limit the risk of relapse and preserve fertility.
OBJECTIVES
Determine the impact of medical or surgical treatment for ectopic pregnancy on future fertility.
DESIGN
Retrospective.
SETTING
Department of obstrtrics and gynecolgy at Ankara Etlik Zübeyde Hanım Women's Health Training and Research Hospital, Ankara, Turkey.
PATIENTS AND METHODS
Patients who were treated for ectopic pregnancy between June 2016 and November 2019 were allocated into two groups. Expectant approach or medical treatment by methotrexate constituted the conservative treatment group while salpingectomy by laparoscopy indicated the surgical treatment group.
MAIN OUTCOME MEASURES
Fertility rates within two years following treatment were evaluated according to treatment options.
SAMPLE SIZE
202 patients.
RESULTS
Of the 202 patients, 128 had medical treatment and 74 patients had surgical treatment for ectopic pregnancy. Of 272 diagnosed with ectopic pregnancy, 70 were excluded for various reasons. Parity and unemployment rate was significantly higher in the surgical treatment (=.006 and =.12, respectively). Moreover, ectopic mass size and serum β-hCG levels were significantly higher in the surgical treatment group (<.001 and <.001, respectively). There were no significant differences between the conservative and surgical treatment groups in time to pregnancy (17.0 months vs 19.0 months, =.255). Similarly, there was no significant difference between the conservative and surgical treatment groups with respect to history of infertility (=.12). There were no significant differences between the conservative and surgical treatment groups in terms of live birth (51.6% vs 44.6%) and ectopic pregnancy (2.3% vs 1.4%) (=.72 for both). There was no significant difference between the conservative and surgical treatment groups with respect to infertility rate (35.9% vs 41.9%, =.72) and admittance to the IVF program (3.9% vs 6.8%, =.39) following ectopic pregnancy treatment.
CONCLUSIONS
Reproductive outcomes did not differ significantly in women undergoing expectant management, medical treatment, and surgery for ectopic pregnancy. This finding suggests that clinicians should not hesitate to act in favor of surgical treatment for ectopic pregnancy even if there were concerns for future fertility.
LIMITATIONS
Retrospective study.
Topics: Humans; Female; Pregnancy; Retrospective Studies; Adult; Methotrexate; Salpingectomy; Conservative Treatment; Pregnancy, Tubal; Laparoscopy; Abortifacient Agents, Nonsteroidal; Turkey; Fertility; Chorionic Gonadotropin, beta Subunit, Human; Fertility Preservation
PubMed: 38853473
DOI: 10.5144/0256-4947.2024.141 -
The Brazilian Journal of Infectious... 2024We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible...
We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible environmental exposures in endemic rural areas, supposedly resulting from reactivation of a latent pulmonary focus secondary to the use of methotrexate for the control of Chikungunya arthropathy. Laboratory investigation ruled out other immunosuppression. Her only symptoms were a dry cough and chest pain. Diagnosis confirmed by needle lung biopsy. There were no abnormalities on physical examination nor evidence of central nervous system involvement. MRI of the total abdomen showed no involvement of other organs. Computed chest tomography showed a favorable evolution under the use of itraconazole (200 mg/day). Different tomographic presentations findings are highlighted when performed before and after treatment. CONCLUSIONS: PCM should be considered even in a woman without a history of consistent environmental exposure and in a non-endemic geographic area.
Topics: Humans; Female; Paracoccidioidomycosis; Middle Aged; Methotrexate; Lung Diseases, Fungal; Chronic Disease; Itraconazole; Tomography, X-Ray Computed; Antifungal Agents; Immunosuppressive Agents
PubMed: 38851212
DOI: 10.1016/j.bjid.2024.103768 -
Journal of Refractive Surgery... May 2024To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus... (Comparative Study)
Comparative Study
PURPOSE
To compare the effects of corneal allogenic intrastromal ring segment (CAIRS) implantation on topographical measurements and visual outcomes of patients with keratoconus with and without corneal cross-linking (CXL) prior to the time of implantation.
METHODS
Sixty-seven eyes with corneal allograft intrastromal ring segment implantation (KeraNatural; Lions VisionGift) due to advanced keratoconus were included in the study. Thirty-seven eyes had no CXL and 30 eyes had had CXL before being referred to the authors. The changes in spherical equivalent (SE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), steep keratometry (K1), flat keratometry (K2), mean keratometry (Kmean), maximum keratometry (Kmax), and thinnest pachymetry were retrospectively analyzed 6 months after the implantation.
RESULTS
The median age was 29 years in the CXL group and 24.0 years in the non-CXL group ( > .05), respectively. All topographical and visual parameters before implantation were similar in both groups ( > .05 for all parameters). At 6 months, CDVA, K1, and Kmean showed higher improvement in the non-CXL group than the CXL group ( = .030, .018, and .039, respectively).
CONCLUSIONS
CAIRS surgery has a flattening effect on both the corneas with and without CXL. The cornea with prior CXL treatment had less flattening effect due to the stiffening effect of prior CXL. .
Topics: Humans; Keratoconus; Corneal Stroma; Cross-Linking Reagents; Visual Acuity; Adult; Male; Female; Prosthesis Implantation; Photosensitizing Agents; Retrospective Studies; Corneal Topography; Young Adult; Prostheses and Implants; Refraction, Ocular; Collagen; Corneal Pachymetry; Riboflavin; Photochemotherapy; Adolescent; Ultraviolet Rays; Corneal Transplantation; Middle Aged; Corneal Cross-Linking
PubMed: 38848056
DOI: 10.3928/1081597X-20240501-01 -
Medicine Jun 2024The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1... (Observational Study)
Observational Study
Impact of TYMS gene polymorphism on the outcome of methotrexate treatment in a sample of Iraqi rheumatoid arthritis patients - identification of novel single nucleotide polymorphism: Cross-sectional study.
The current work aims to evaluate the association between genetic mutations in thymidylate synthetase (TYMS gene in exon1 and partial regions of promotor and intron 1 [877 bp, 657,220-658,096 bp]) and the therapeutic outcomes for rheumatoid arthritis (RA) Iraqi patients. An observational cross-sectional study involving 95 RA patients with established RA patients based on their methotrexate treatment responsiveness. Genetic sequencing of the TYMS gene was performed for all patients according to the instruction manuals of the sequencing company (Macrogen Inc. Geumchen, South Korea). Four polymorphisms were identified by sequencing 95 randomly selected patients in the noncoding region of TYMS. Three of these polymorphisms were found in the NCBI database's dbSNP (rs2853741, rs2606241, and rs2853742 SNPs), and one SNP polymorphism is novel (657334). The CTAT (657334, rs2853741, rs2606241, and rs2853742 SNPs) haplotype was significantly associated with responder with odd ratio, 95% confidence interval: 0.506, 0.281-0.912 (P value = .022). In contrast, the other haplotypes were not associated with MTX responsiveness. In the multivariate analysis, after adjusting to the effect of age, sex, smoking, and disease duration, the TCrs2853741 genotype was associated with non-responders (P value = .030). In contrast, the ACrs260641 genotype, after adjusting to the effect of age, sex, and smoking, was associated with non-responders (P value = .035). Genetic polymorphism of the TYMS gene, especially in TCrs2853741 and ACrs260641, predicts non-responder to MTX treatment in RA, while the presence of the CTAT haplotype predicts a good response to MTX treatment.
Topics: Humans; Cross-Sectional Studies; Polymorphism, Single Nucleotide; Male; Arthritis, Rheumatoid; Female; Methotrexate; Middle Aged; Antirheumatic Agents; Adult; Iraq; Thymidylate Synthase; Haplotypes; Treatment Outcome
PubMed: 38847705
DOI: 10.1097/MD.0000000000038448