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Background: Nanocarrier-based systems have cultivated significant improvements in prostate cancer therapy. However, the efforts are still limited in clinical applicability, and more research is required for the development of effective strategies. Here, we describe a novel nanoliposomal system for targeted apoptotic gene delivery to prostate cancer. Methods: Poly (2-ethyl-2-oxazoline) (PEtOx) dioleoyl phosphatidylethanolamine (DOPE) nanoliposomes were conjugated with the prostate-specific membrane antigen (PSMA)-targeting peptide GRFLTGGTGRLLRIS (P563) and loaded with BikDDA, a mutant form of the proapoptotic Bik. We selected 22Rv1 cells with moderate upregulation of PSMA to test the in vitro uptake, cell death, and in vivo anticancer activity of our formulation, P563-PEtOx-DOPE-BikDDA. Results: BikDDA was upregulated in 22Rv1 cells, inducing cell death, and CD-1 nude mice xenografts administered with the formulation showed significant tumor regression. Conclusion: We suggest that P563-PEtOx-DOPE-BikDDA nanoliposomes can serve as prominent gene carriers against prostate cancer.
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In recent years, multifunctional nanocarriers that provide simultaneous drug delivery and imaging have attracted enormous attention, especially in cancer treatment. In this research, a biocompatible fluorescent multifunctional nanocarrier is designed for the co-delivery of capsaicin (CPS) and nitrogen-doped graphene quantum dots (N-GQDs) using the pH sensitive amphiphilic block copolymer (poly(2-ethyl-2-oxazoline)-b-poly(ε-caprolactone), PEtOx-b-PCL). The effects of the critical formulation parameters (the amount of copolymer, the concentration of poly(vinyl alcohol) (PVA) as a stabilizing agent in the inner aqueous phase, and volume of the inner phase) are evaluated to achieve optimal nanoparticle (NP) properties using Central Composite Design. The optimized NPs demonstrated a desirable size distribution (167.8 ± 1.4 nm) with a negative surface charge (-19.9 ± 0.4) and a suitable loading capacity for CPS (70.80 ± 0.05%). The CPS & N-GQD NPs are found to have remarkable toxicity on human breast adenocarcinoma cell line (MCF-7). The solid fluorescent signal is acquired from cells containing multifunctional NPs, according to the confocal microscope imaging results, confirming the significant cellular uptake. This research illustrates the enormous potential for cellular imaging and enhanced cancer therapy offered by multifunctional nanocarriers that combine drug substances with the novel fluorescent agents.
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The COVID-19 pandemic revealed the need for therapeutic and pharmaceutical molecule development in a short time with different approaches. Although boosting immunological memory by vaccination was the quickest and robust strategy, still medication is required for the immediate treatment of a patient. A popular approach is the mining of new therapeutic molecules. Peptide-based drug candidates are also becoming a popular avenue. To target whole pathogenic viral agents, peptide libraries can be employed. With this motivation, we have used the 12mer M13 phage display library for selecting SARS-CoV-2 targeting peptides as potential neutralizing molecules to prevent viral infections. Panning was applied with four iterative cycles to select SARS-CoV-2 targeting phage particles displaying 12-amino acid-long peptides. Randomly selected peptide sequences were synthesized by a solid-state peptide synthesis method. Later, selected peptides were analyzed by the quartz crystal microbalance method to characterize their molecular interaction with SARS-CoV-2's S protein. Finally, the neutralization activity of the selected peptides was probed with an in-house enzyme-linked immunosorbent assay. The results showed that scpep3, scpep8, and scpep10 peptides have both binding and neutralizing capacity for S1 protein as a candidate for therapeutic molecule. The results of this study have a translational potential with future in vivo and human studies.
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BACKGROUND: Inflammatory bowel diseases (IBD) are chronic diseases that are not fully understood. Drugs in use can only be applied for a short time due to their side effects. Therefore, research is needed to develop new treatment approaches. In addition, it has been proven that IBD causes degeneration in the enteric nervous system (ENS). In recent years, it has been discussed that probiotics may have positive effects in the prevention and treatment of inflammatory enteric degeneration. Akkermansia muciniphila (A. muciniphila) is an anaerobic bacterium found in the mucin layer of the intestinal microbiota. It has been found that the population of A. muciniphila decreases in the case of different diseases. In light of this information, the curative effect of A. muciniphila application on colitis-induced inflammation and enteric degeneration was investigated. METHODS: In this study, 5 weeks of A. muciniphila treatment in Trinitro-benzene-sulfonic acid (TNBS)-induced chronic colitis model was investigated. Colon samples were examined at microscopic, biochemical, and molecular levels. Fecal samples were collected before, during, and after treatment to evaluate the population changes in the microbiota. Specific proteins secreted from the ENS were evaluated, and enteric degeneration was examined. RESULTS: As a result of the research, the ameliorative effects of A. muciniphila were shown in the TNBS colitis model-induced inflammation and ENS damage. DISCUSSION: In light of these results, A. muciniphila can potentially be evaluated as a microbiome-based treatment for IBD with further clinical and experimental studies.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Mice , Animals , Neuroinflammatory Diseases , Base Composition , Sequence Analysis, DNA , RNA, Ribosomal, 16S , Phylogeny , Colitis/chemically induced , Colitis/therapy , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/therapy , Inflammatory Bowel Diseases/microbiology , Verrucomicrobia/genetics , Inflammation , Chronic Disease , AkkermansiaABSTRACT
This study focuses on creating a specialized nanogel for targeted drug delivery in cancer treatment, specifically targeting prostate cancer. This nanogel (referred to as SGK 636/Peptide 563/PEtOx nanogel) is created using hydrophilic poly(2-ethyl-2-oxazoline) (PEtOx) through a combination of living/cationic ring-opening polymerization (CROP) and alkyne-azide cycloaddition (CuAAC) "click" chemical reactions. A fluorescent probe (BODIPY) is also conjugated with the nanogel to monitor drug delivery. The characterizations through 1 H-NMR, and FT-IR, SEM, TEM, and DLS confirm the successful production of uniform, and spherical nanogels with controllable sizes (100 to 296 nm) and stability in physiological conditions. The biocompatibility of nanogels is evaluated using MTT cytotoxicity assays, revealing dose-dependent cytotoxicity. Drug-loaded nanogels exhibited significantly higher cytotoxicity against cancer cells in vitro compared to drug-free nanogels. Targeting efficiency is examined using both peptide-conjugated and peptide-free nanogels, with the intracellular uptake of peptide 563-conjugated nanogels by tumor cells being 60-fold higher than that of nanogels without the peptide. The findings suggest that the prepared nanogel holds great potential for various drug delivery applications due to its ease of synthesis, tunable functionality, non-toxicity, and enhanced intracellular uptake in the tumor region.
Subject(s)
Drug Delivery Systems , Polyethyleneimine , Prostatic Neoplasms , Humans , Male , Nanogels , Spectroscopy, Fourier Transform Infrared , Polyethylene Glycols/chemistry , Prostatic Neoplasms/drug therapy , Peptides/pharmacology , Drug Carriers/chemistryABSTRACT
We present a structured approach to combine explainability of artificial intelligence (AI) with the scientific method for scientific discovery. We demonstrate the utility of this approach in a proof-of-concept study where we uncover biomarkers from a convolutional neural network (CNN) model trained to classify patient sex in retinal images. This is a trait that is not currently recognized by diagnosticians in retinal images, yet, one successfully classified by CNNs. Our methodology consists of four phases: In Phase 1, CNN development, we train a visual geometry group (VGG) model to recognize patient sex in retinal images. In Phase 2, Inspiration, we review visualizations obtained from post hoc interpretability tools to make observations, and articulate exploratory hypotheses. Here, we listed 14 hypotheses retinal sex differences. In Phase 3, Exploration, we test all exploratory hypotheses on an independent dataset. Out of 14 exploratory hypotheses, nine revealed significant differences. In Phase 4, Verification, we re-tested the nine flagged hypotheses on a new dataset. Five were verified, revealing (i) significantly greater length, (ii) more nodes, and (iii) more branches of retinal vasculature, (iv) greater retinal area covered by the vessels in the superior temporal quadrant, and (v) darker peripapillary region in male eyes. Finally, we trained a group of ophthalmologists (N=26) to recognize the novel retinal features for sex classification. While their pretraining performance was not different from chance level or the performance of a nonexpert group (N=31), after training, their performance increased significantly (p<0.001, d=2.63). These findings showcase the potential for retinal biomarker discovery through CNN applications, with the added utility of empowering medical practitioners with new diagnostic capabilities to enhance their clinical toolkit.
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Many empirical studies suggest that samples of continuous-time signals taken at locations randomly deviated from an equispaced grid (i.e., off-the-grid) can benefit signal acquisition, e.g., undersampling and anti-aliasing. However, explicit statements of such advantages and their respective conditions are scarce in the literature. This paper provides some insight on this topic when the sampling positions are known, with grid deviations generated i.i.d. from a variety distributions. By solving a square-root LASSO decoder with an interpolation kernel we demonstrate the capabilities of nonuniform samples for compressive sampling, an effective paradigm for undersampling and anti-aliasing. For functions in the Wiener algebra that admit a discrete s-sparse representation in some transform domain, we show that O(spolylogN) random off-the-grid samples are sufficient to recover an accurate N2-bandlimited approximation of the signal. For sparse signals (i.e., sâªN), this sampling complexity is a great reduction in comparison to equispaced sampling where O(N) measurements are needed for the same quality of reconstruction (Nyquist-Shannon sampling theorem). We further consider noise attenuation via oversampling (relative to a desired bandwidth), a standard technique with limited theoretical understanding when the sampling positions are non-equispaced. By solving a least squares problem, we show that O(NlogN) i.i.d. randomly deviated samples provide an accurate N2-bandlimited approximation of the signal with suppression of the noise energy by a factor â¼1log(N).
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Deep learning (DL) techniques have seen tremendous interest in medical imaging, particularly in the use of convolutional neural networks (CNNs) for the development of automated diagnostic tools. The facility of its non-invasive acquisition makes retinal fundus imaging particularly amenable to such automated approaches. Recent work in the analysis of fundus images using CNNs relies on access to massive datasets for training and validation, composed of hundreds of thousands of images. However, data residency and data privacy restrictions stymie the applicability of this approach in medical settings where patient confidentiality is a mandate. Here, we showcase results for the performance of DL on small datasets to classify patient sex from fundus images-a trait thought not to be present or quantifiable in fundus images until recently. Specifically, we fine-tune a Resnet-152 model whose last layer has been modified to a fully-connected layer for binary classification. We carried out several experiments to assess performance in the small dataset context using one private (DOVS) and one public (ODIR) data source. Our models, developed using approximately 2500 fundus images, achieved test AUC scores of up to 0.72 (95% CI: [0.67, 0.77]). This corresponds to a mere 25% decrease in performance despite a nearly 1000-fold decrease in the dataset size compared to prior results in the literature. Our results show that binary classification, even with a hard task such as sex categorization from retinal fundus images, is possible with very small datasets. Our domain adaptation results show that models trained with one distribution of images may generalize well to an independent external source, as in the case of models trained on DOVS and tested on ODIR. Our results also show that eliminating poor quality images may hamper training of the CNN due to reducing the already small dataset size even further. Nevertheless, using high quality images may be an important factor as evidenced by superior generalizability of results in the domain adaptation experiments. Finally, our work shows that ensembling is an important tool in maximizing performance of deep CNNs in the context of small development datasets.
Subject(s)
Deep Learning , Humans , Neural Networks, Computer , Fundus OculiABSTRACT
In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH4 , the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by 1 H-NMR, 13 C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC50 values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC50 values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol (4 d) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol (7 d) were determined to be 18.1â µg and 35.1â µg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.
Subject(s)
Antifungal Agents , Antioxidants , Antioxidants/chemistry , Antifungal Agents/chemistry , Anti-Bacterial Agents/chemistry , Amines/pharmacology , Spectroscopy, Fourier Transform Infrared , Schiff Bases/chemistry , Gram-Negative Bacteria , Gram-Positive Bacteria , SkeletonABSTRACT
INTRODUCTION: Hair tourniquet syndrome (HTS) is a rare surgical emergency caused by a hair or thread wrapping around an appendage. We aimed to present our clinical experience with HTS of toes and attract physicians' attention to this rare entity. METHODS: Between January 2012 and September 2022; 26 patients (25 pediatric and one adult case) were treated for HTS. All pediatric cases were treated surgically under loop magnification. The adult patient was treated nonsurgically. The patient's age, gender, affected appendage and side, duration of symptoms, and postoperative complications were recorded. RESULTS: Thirty-six toes of 25 patients (13 boys, 11 girls, and a male adult) were included in the study. The mean age of pediatric patients was 126.6 days. The third toe was the most affected (n:16), followed by the fourth (n:8). In seven patients more than one was affected. CONCLUSION: HTS should be treated as soon as possible when diagnosed to prevent further complications including appendage loss.
Subject(s)
Ischemia , Tourniquets , Female , Humans , Male , Child , Infant , Tourniquets/adverse effects , Ischemia/etiology , Ischemia/surgery , Toes/surgery , Hair , SyndromeABSTRACT
This article describes the development of a mild method for the N-dealkylation of tertiary amines via photoredox catalysis and its application in late-stage functionalization. Using the developed method, more than 30 diverse aliphatic, aniline-type, and complex substrates are shown to undergo N-dealkylation, providing a method with broader functional group tolerance compared to methods found in the literature. The scope also includes tertiary and secondary amine molecules with complex substructures and drug substrates. Interestingly, α-oxidation to imines was observed in several cyclic substructures instead of N-dealkylation, suggesting that imines are relevant reaction intermediates.
Subject(s)
Amines , Imines , Amines/chemistry , Oxidation-Reduction , Catalysis , Imines/chemistry , DealkylationABSTRACT
Prostate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides. The targeting strategy coupling the drugs with nanotechnology helps to overcome the most common barriers, such as high toxicity and side effects. Prostate-specific membrane antigen has emerged as a promising target molecule for prostate cancer and shown to be targeted with high affinity by GRFLTGGTGRLLRIS peptide known as peptide 563 (P563). Here, we aimed to assess the in vitro and in vivo targeting efficiency, safety, and efficacy of P563-conjugated, docetaxel (DTX)-loaded polymeric micelle nanoparticles (P563-PEtOx-co-PEI30%-b-PCL-DTX) against prostate cancer. To this end, we analyzed the cytotoxic activity of P563-PEtOx-co-PEI30%-b-PCL and P563-PEtOx-co-PEI30%-b-PCL-DTX by a cell proliferation assay using PNT1A and 22Rv1 cells. We have also determined the targeting selectivity of P563-PEtOx-co-PEI30%-b-PCL-FITC by flow cytometry and assessed the induction of cell death by western blot and TUNEL assays for P563-PEtOx-co-PEI30%-b-PCL-DTX in 22Rv1 cells. To investigate the in vivo efficacy, we administered DTX in the free form or in polymeric micelle nanoparticles to athymic CD-1 nu/nu mice 22Rv1 xenograft models and performed histopathological analyses. Our study showed that targeting prostate cancer with P563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelles could exert a potent anti-cancer activity with low side effects.
Subject(s)
Antineoplastic Agents , Prostatic Neoplasms , Mice , Male , Animals , Humans , Docetaxel , Micelles , Quality of Life , Taxoids/pharmacology , Taxoids/therapeutic use , Taxoids/chemistry , Antineoplastic Agents/chemistry , Polymers , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Peptides/therapeutic use , Cell Line, TumorABSTRACT
We aimed to investigate the effect of simulation-supported breastfeeding program given to women in pregnancy during the COVID-19 pandemic period on breastfeeding success, breastfeeding self-efficacy, and mother-infant attachment. They carried out this study 73 pregnant women who presented to the obstetrics and gynecology clinic of a hospital and were selected by using the simple random sampling method. The researchers used a quasi-experimental design in this study. After the simulation-supported breastfeeding program, they found that breastfeeding success and breastfeeding self-efficacy were increased in the experimental group compared to the control group. The researchers were used the structural equation model, regression analysis, and independent samples t-test in the data analysis. The education given to pregnant women in this period when social interaction decreases becomes more important. Researchers are recommended that breastfeeding education should start in the antenatal period and continue in the postpartum period by using different education methods together. Simulation-supported breastfeeding program is a model that can be used to provide breastfeeding education for pregnant women in public health emergencies such as the COVID-19 pandemic. With this program, the number of visits to the hospital for breastfeeding education will decrease, and more remote counseling will be provided.
Subject(s)
Breast Feeding , COVID-19 , Infant , Female , Pregnancy , Humans , Breast Feeding/psychology , Turkey , Pandemics , Mothers/psychologyABSTRACT
The Karadon mine, where field studies were carried out, is located in the north west of Turkey and is considered to be a highly gaseous coal mine. Explosives and ignition systems used in underground coal mines are determined by laws, statutes, regulations and strict rules. Restrictions arising from legal requirements, such as restrictions on charging and stemming lengths and blasting agents to be used, make the use of well-known tunnel blasting techniques difficult or sometimes not possible. In such cases, the designs made with the equations given in the literature must be revised and rearranged. The objective of this study is to recommend solutions to the blasting difficulties that are encountered in gaseous underground coal mines in which there are limitations arising from legal requirements. This study summarizes and analyses the blasting practices currently employed at Karadon mine along with their disadvantages. New blasting designs were then made using the methods suggested in the literature, and these designs were revised according to legal requirements. By keeping the charge concentration constant relative to its original value, the burden and spacing distances were adjusted. As a result of this study, it has been seen that rearrangement by keeping the charge concentration constant compared to its original value is an appropriate engineering solution.
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BACKGROUND: The aim of this study is to evaluate the musculoskeletal injuries related with 24 January 2020 Elazig/Türkiye earthquake and their treatment protocols. METHODS: Data of patients applied to Inönü University Medical Faculty Hospital, Elazig Training and Research Hospital and Malatya Training and Research Hospital emergency departments within 48 h after the earthquake, were evaluated retrospectively. Age, gender, soft tissue injuries and sites, fracture sites and types, fracture etiology, and treatment methods were evaluated. RESULTS: 247 patients were evaluated. 118 were women and 139 were men. There were 24 (9.7%) pediatric patients. Mean age was 37.3 (1-92) years. Waist majority of injuries were simple soft-tissue injuries. There were 103 fractures in 86 patients. Thirty-eight patients' fractures were treated surgically. CONCLUSION: Every major disaster warrants retrospective studies so we can learn how to improve all levels of Emergency Medical Services. Great proportion of Elazig earthquake victims had only simple soft tissue injuries such as sprain, laceration, or contusion. Many patients were injured due to reasons indirectly related to the destruction brought by the earthquake. Panic caused by the earth-quake caused more injury than the destruction it brought.
Subject(s)
Disasters , Earthquakes , Emergency Medical Services , Fractures, Bone , Soft Tissue Injuries , Wounds and Injuries , Adult , Child , Female , Fractures, Bone/epidemiology , Fractures, Bone/etiology , Humans , Male , Retrospective Studies , Soft Tissue Injuries/epidemiology , Soft Tissue Injuries/etiologyABSTRACT
The aim of the study was to investigate the reasons for Turkish obstetricians having self-caesarean section on maternal request (CSMR) and their attitudes and practices related to CSMR and vaginal birth after caesarean section (VBAC). The questionnaire form constructed by the authors was sent online to obstetricians working in different cities of Turkey. A total of 206 obstetricians participated and answered a self-administered questionnaire. The self-birth preferences were as follows: 17% had a vaginal delivery (VD), 61.2% had a caesarean section (CS), 4.9% had both VD and CS. Of the participants with CS, 56.3% had CSMR. The most common reason for their having self-CSMR was that it was 'safe for the baby'. The most common reason for performing CSMR with their patients was 'due to birth anxiety and phobia'. Fifty-five percent of the participants said that they first recommended VD. The most common concern related to VBAC was 'I'm afraid of legal sanctions about complications'. Although many Turkish obstetricians recommend VD to their patients, they are afraid of the complaints/trials related to unforeseen complications during VD. IMPACT STATEMENTWhat is already known on this subject? Caesarean section (CS) rates all over the world and in Turkey are rising. The exact frequency of CS on maternal request (CSMR) is not known, but it is estimated to be between 4% and 18%.What do the results of this study add? Although Turkish obstetricians had high self-CSMR rates, they thought that it was more correct to direct patients to vaginal delivery (VD). Obstetricians are afraid of unforeseen complications during VD and related complaints and legal trials.What are the implications of these findings for clinical practice and/or further research? Physicians expect improvements in the judgement and punishment issues related to unforeseen complications in the birth process. Besides the actual rates of CSMR need to be reported in the literature and why obstetricians perform CSMR needs to be investigated globally.
Subject(s)
Physicians , Vaginal Birth after Cesarean , Attitude of Health Personnel , Cesarean Section/adverse effects , Female , Humans , Pregnancy , Turkey/epidemiology , Vaginal Birth after Cesarean/adverse effectsABSTRACT
OBJECTIVE: The aim of this study was to investigate the serum levels of mild, severe preeclamptic pregnants and normotensive pregnant women to determine whether there is a correlation between preeclampsia and their serum levels. METHODS: This prospective case-control study included 48 preeclamptic and 39 healthy normotensive pregnants. The control group was composed of body mass index and age matched pregnant women. Preeclamptic patients were divided into two groups as mild preeclampsia and severe preeclampsia. Serum apelin levels were determined by EnzymeImmunometricAssay (EIA) biochemical test. RESULTS: Serum apelin levels were found to be significantly lower in the preeclampsia group. It was 0.75 ± 0.24 ng/ml in mild preeclampsia and 0.55 ± 0.18 ng/ml in the severe preeclampsia and 0.91 ± 0.20 ng/ml in the control group. There was a strong inverse correlation between serum apelin levels and Systolic Blood Pressure (SBP) (r: -0.429 p: 0.002). CONCLUSIONS: In conclusion, the role of apelin and apelinergic system in cardiovascular system and placental development and their place in preeclampsia is still an issue. In preeclampsia, the deterioration of the cardiovascular protective effect of apelin by other enzymes may also contribute to the deterioration of fetal development. More detailed studies are needed.
Subject(s)
Apelin/blood , Pre-Eclampsia , Blood Pressure/physiology , Case-Control Studies , Female , Humans , Placenta , PregnancyABSTRACT
OBJECTIVE: Reactive oxygen species and oxygen free radicals cause oxidative damage to lipids, proteins, and cell DNA in the cell membrane. Although many DNA products are produced during oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine (8-OHdG) is the most common one, since it can be produced in in vivo environment. In recent years, diving has been done quite frequently for business and sports purposes all over the world. Increased environmental pressure in diving leads to hyperoxia and causes oxidative stress. METHODS: The acute effects of diving on DNA damage were evaluated by comparing 8-hydroxy-2'-deoxyguanosine values of 15 professional diver groups before and after diving. In addition to the demographic characteristics, the serum 8-hydroxy-2'-deoxyguanosine levels of these 15 divers were compared with the control group consisting of nondiving medical students to examine the chronic effect of diving on DNA damage. RESULTS: After deep dive, the amount of 8-hydroxy-2'-deoxyguanosine increased significantly in the diver group and acute DNA damage was observed (T1: 38.86±4.7; T2: 51.77±4.53; p<0.05). In the control group, the amount of 8-hydroxy-2'-deoxyguanosine was insignificant (C1: 47.48±3.73; T1: 38.86±4.7; p>0.05). CONCLUSIONS: It was found that air dives caused an increase in serum 8-hydroxy-2'-deoxyguanosine levels, leading to acute oxidative stress and aging. However, there is no chronic side effect, according to the study of samples taken from the control group. This was thought to be due to the relative sedentary life of the control group. The duration of the effect or the ability to return to normal values should be investigated with further studies planned with large populations.
Subject(s)
DNA Damage , Deoxyguanosine , 8-Hydroxy-2'-Deoxyguanosine , Biomarkers , Humans , Oxidative Stress , Reactive Oxygen SpeciesABSTRACT
Flexor tendon entrapment (FTE) is a rare and usually lately diagnosed complication of pediatric forearm fractures. In this case report, we present a case of a neglected ring and little finger flexor digitorum profundus (FDP) entrapment after closed reduction of both bone forearm fracture and treated five years later due to late diagnosis. A 20-year-old man presented to outpatient clinic with flexion contracture of ring and little finger that occurred after both-bone forearm fracture treated with closed reduction and long arm cast five years ago. On his physical examination, flexion contracture of ring and index fingers was thought to be due to entrapment of tendons at the level of forearm and surgically released. Five years after surgical treatment for FTE, the patient had full range of motions at both fingers. He had no additional complaint. In conclusion, FTE is a rare complication after both bone forearm fractures. It should be kept in mind in the treatment of both bone forearm fractures. Surgical treatment of FTE in late cases is an effective procedure with excellent results.
Subject(s)
Forearm Injuries , Radius Fractures , Trigger Finger Disorder , Adult , Child , Forearm/surgery , Forearm Injuries/surgery , Humans , Male , Radius Fractures/surgery , Tendons , Young AdultABSTRACT
Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOx-DOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy.