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1.
J Biomater Sci Polym Ed ; : 1-22, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38885181

ABSTRACT

Molecularly imprinted polymers (MIPs) have garnered the interest of researchers in the drug delivery due to their advantages, such as exceptional durability, stability, and selectivity. In this study, a biocompatible MIP drug adsorption and delivery system with high loading capacity and controlled release, was prepared based on chitosan (CS) and graphene quantum dots (GQDs) as the matrix, and the anticancer drug oxaliplatin (OXAL) as the template. Additionally, samples without the drug (non-imprinted polymers, NIPs) were created for comparison. GQDs were produced using the hydrothermal method, and samples underwent characterization through FTIR, XRD, FESEM, and TGA. Various experiments were conducted to determine the optimal pH for drug adsorption, along with kinetic and isotherm studies, selectivity assessments, in vitro drug release and kinetic evaluations. The highest drug binding capacity was observed at pH 6.5. The results indicated the Lagergren-first-order kinetic model (with rate constant of 0.038 min-1) and the Langmuir isotherm (with maximum adsorption capacity of 17.15 mg g-1) exhibited better alignment with the experimental data. The developed MIPs displayed significant selectivity towards OXAL, by an imprinting factor of 2.88, in comparison to two similar drugs (cisplatin and carboplatin). Furthermore, the analysis of the drug release profile showed a burst release for CS-Drug (87% within 3 h) at pH 7.4, where the release from the CS-GQD-Drug did not occur at pH 7.4 and 10; instead, the release was observed at pH 1.2 in a controlled manner (100% within 28 h). Consequently, this specific OXAL adsorption and delivery system holds promise for cancer treatment.

2.
Genomics Inform ; 22(1): 9, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38926832

ABSTRACT

OBJECTIVE: Cervical cancer (CxCa) stands as a significant global health challenge, ranking fourth in cancer-related mortality among the female population. While chemotherapy regimens have demonstrated incremental progress in extending overall survival, the outlook for recurrent CxCa patients remains disheartening. An imperative necessity arises to delve into innovative therapeutic avenues, with molecular targeted therapy emerging as a promising candidate. Previous investigations have shed light on the therapeutic effectiveness of five distinct herbal compounds, epicatechin, curcumin, myricetin, jatrorrhizine, and arborinine, within the context of CxCa. METHODS: A systems biology approach was employed to discern differentially expressed genes (DEGs) in CxCa tissues relative to healthy cervical epithelial tissues. A protein-protein interaction network (PPIN) was constructed, anchored in the genes related to CxCa. The central genes were discerned within the PPIN, and Kaplan-Meier survival curves explored their prognostic significance. An assessment of the binding affinity of the selected herbal compounds to the master regulator of prognostic markers in CxCa was conducted. RESULTS: A significant correlation between the overexpression of MYC, IL6, JUN, RRM2, and VEGFA and an adverse prognosis in CxCa was indicated. The regulation of these markers is notably influenced by the transcription factor CEBPD. Molecular docking analysis indicated that the binding affinity between myricetin and the CEBPD DNA binding site was robust. CONCLUSION: The findings presented herein have unveiled pivotal genes and pathways that play a central role in the malignant transformation of CxCa. CEBPD has emerged as a potential target for harnessing the therapeutic potential of myricetin in this context.

3.
Digit Health ; 10: 20552076241257146, 2024.
Article in English | MEDLINE | ID: mdl-38812853

ABSTRACT

Objective: Electronic patient-reported outcome (ePRO) systems hold promise for revolutionizing communication between cancer patients and healthcare providers across various care settings. This systematic review explores the multifaceted landscape of ePROs in cancer care, encompassing their advantages, disadvantages, potential risks, and opportunities for improvement. Methods: In our systematic review, we conducted a rigorous search in Scopus, Web of Science, and PubMed, employing comprehensive medical subject heading terms for ePRO and cancer, with no date limitations up to 2024. Studies were critically appraised and thematically analyzed based on inclusion and exclusion criteria, including considerations of advantages, disadvantages, opportunities, and threats. Findings: Analyzing 85 articles revealed 69 themes categorized into four key areas. Advantages (n = 14) were dominated by themes like "improved quality of life and care." Disadvantages (n = 26) included "limited access and technical issues." Security concerns and lack of technical skills were prominent threats (n = 10). Opportunities (n = 19) highlighted advancements in symptom management and potential solutions for technical challenges. Conclusion: This review emphasizes the crucial role of continuous exploration, integration, and innovation in ePRO systems for optimizing patient outcomes in cancer care. Beyond traditional clinical settings, ePROs hold promise for applications in survivorship, palliative care, and remote monitoring. By addressing existing limitations and capitalizing on opportunities, ePROs can empower patients, enhance communication, and ultimately improve care delivery across the entire cancer care spectrum.

4.
Arch Rheumatol ; 39(1): 123-132, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38774696

ABSTRACT

Objectives: Considering the role of T helper (Th)17 cells in the pathogenesis of ankylosing spondylitis (AS), the aim of this study was to determine the correlation between aryl hydrocarbon receptor (AHR) gene expression and the expression of Th17-related genes including interleukin (IL)-17 and RAR-related orphan receptor gamma t (RORγt) transcription factor. Patients and methods: Thirty patients with AS (26 males, 4 females; mean age: 36.1±8.1 years) and 30 age- and sex-matched healthy individuals (26 males, 4 females; mean age: 36.2±14.6 years) were recruited for the case-control study between June 2021 and January 2022. Ribonucleic acid (RNA) was extracted from peripheral blood cells and expression levels of AHR, IL-17, RORγt, and AHR repressor (AHRR) genes were evaluated using real-time polymerase chain reaction technique. The serum level of IL-17 was evaluated with enzyme-linked immunosorbent assay. Results: The results showed a nonsignificant elevation of AHR, IL-17, and RORγt gene expression in the patient group compared to the control. There was a direct correlation between AHR gene expression and IL-17 and RORγt genes and a negative correlation between AHR and AHRR expression. Moreover, AHR gene expression showed a weak correlation with disease activity indices, including Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Global Score, and Ankylosing Spondylitis Quality of Life. Moreover, the serum level of IL-17 was higher in AS patients compared to the healthy group (p=0.02). Conclusion: Upregulated expression of the AHR gene in ankylosing spondylitis and its correlation with IL-17 and ROR-γ t gene expression suggests that it could be a potential diagnostic and therapeutic target for AS.

5.
Oxf Med Case Reports ; 2024(2): omad159, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38370505

ABSTRACT

Rheumatoid arthritis (RA) is a chronic inflammatory condition primarily affecting the musculoskeletal system but can often involve other organ systems as well. Rheumatoid meningitis is a rare central nervous system (CNS) manifestation of RA characterized by pachymeningeal and leptomeningeal enhancement. Herein, we present a case of a 64-year-old male who presented with left lower extremity weakness and witnessed seizures. The diagnostic work-up, including lumbar puncture, brain MRI and meningeal biopsy ruled out malignancy and were consistent with the diagnosis of rheumatoid meningitis. The patient was discharged on high-dose steroids along with anti-seizure medications. On subsequent follow-up visits, the patient remained seizure-free.

6.
Adv Biomed Res ; 12: 208, 2023.
Article in English | MEDLINE | ID: mdl-38073728

ABSTRACT

Background: The aim of this study was to assess the prevalence of insulin resistance (HOMA-IR) between patients with and without thyroid nodules. Materials and Methods: This case-control study was performed on 86 patients with normal Thyroid-stimulating hormone (TSH) level (0.5-4.5 mIU/L) with thyroid nodules, who referred to Imam Khomeini and Golestan Hospitals (Ahvaz, Iran). Furthermore, 43 nonnodule patients with normal TSH level and normal thyroid ultrasonography were recruited from the general population as control group. The insulin resistance was evaluated for them made and the HOMA-IR ≥2.5 was defined as insulin resistance. Results: The mean of HOMA-IR value was significantly higher in thyroid nodule patients compared to controls (3.02 ± 1.92 vs. 1.10 ± 1.55; P < 0.001). Insulin resistance was seen in 49 thyroid nodule patients (57.0%), and 4 patients (9.3%) in the control group (P < 0.0001). Waist circumference, body mass index, fasting blood sugar, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and insulin levels were significantly higher in the thyroid nodule group. Conclusions: Our study shows there is an association between insulin resistance and thyroid nodules. The patients with thyroid nodules have higher HOMA-IR value.

7.
Inorg Chem ; 62(49): 20372-20389, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-37996778

ABSTRACT

Bi2MoO6/TiO2 heterojunction photocatalysts were constructed by depositing Bi2MoO6 nanosheets on TiO2 nanobelts' surface using a solvothermal method, and the surface of the optimum Bi2MoO6/TiO2 composite was decorated with copper and/or platinum nanoparticles. The synthesized samples were investigated for the CO2 photocatalytic reduction. The structural and optical properties of synthesized photocatalysts were characterized by XRD, FESEM, EDX, N2-physisorption, Raman, TPD-CO2, DRS, and PL analysis. The Bi2MoO6/TiO2 composite with different molar ratios of Bi2MoO6 to TiO2 (1, 1/2, 1/3, 1/4, 1/5, and 1/6) showed enhanced photocatalytic activity compared to pure Bi2MoO6 and TiO2. In comparison to bulk Bi2MoO6 and TiO2, the formation of a heterojunction between Bi2MoO6 and TiO2 leads to enhanced CO2 adsorption capacity. The enhanced performance of composites can be ascribed to the improved efficiency of light harvesting in the visible light range and suppressing charge recombination. The composite photocatalytic activity indicated that the ratio of Bi2MoO6 to TiO2 in the composite samples influenced the photocatalytic performance. The Bi2MoO6/TiO2 composite with 1/4 molar ratio had the best performance in 8 h (36.4 µmol/gcat), which was about 10 and 3 times higher than TiO2 and Bi2MoO6 photocatalysts, respectively. Under UV-visible light irradiation, the Pt-Cu@BMT4 sample produced the highest amount of methane (83.6 µmol/gcat) during CO2 photoreduction. During four irradiation cycles, the Pt-Cu@BMT4 sample exhibited superior stability with less than 5% decrease in methane production.

8.
BMC Neurol ; 23(1): 408, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37978455

ABSTRACT

INTRODUCTION: Multiple sclerosis (MS) is the most prevalent disease of the central nervous system that affects the behavioral characteristics and lifestyle of patients. This study aimed to determine the social stigma and its relationship with quality of life in people with MS referring to the Jahrom MS Association. METHOD: This cross-sectional study was conducted on MS patients who are members of the MS Association of Jahrom City in Fars province, southern Iran in 2022. The samples were selected by census method. The number of participants remain 223 people. The data was collected using a standard two-part demographic and Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaire and a researcher-made 20-question Social stigma questionnaire which validity and reliability were measured. Data analysis was done in a descriptive way (frequency, percentage, mean and standard deviation), univariate regression and multivariable linear regression. Data analysis was done using SPSS version 17 and at a significance level of less than 0.05. RESULT: Based on univariate regression, marriage [B = 0.2, p-value = 0.004], physical health [B = 0.4, p-value < 0.001], emotional well-being [B = 0.4, p-value = 0.001], cognitive functioning [B = 0.4, p-value < 0.001], health distress [B = 0.5, p-value < 0.001] had a positive and significant relationship with patients' quality of life. Duration of disease [B=-0.2, p-value < 0.001], physical role limitations [B=-0.4, p-value < 0.001], emotional role limitations [B=-0.5, p-value < 0.001], pain [B=-0.4, p-value < 0.001], energy [B=-0.3, p-value = 0.02], health perception [B=-0.3, p-value = 0.001], social functioning [B=-0.4, p-value < 0.001], sexual function [B=-0.3, p-value < 0.001], change in health [B=-0.3, p-value < 0.001], sexual function satisfaction [B=-0.3, p-value < 0.001] and social stigma [B=-0.3, p-value < 0.001] had a negative and significant relationship with patients' quality of life (p < 0.05). CONCLUSION: The study has emphasized the relationship between the extent and severity of symptoms and disorders with the quality of life of people with MS. The results of the study showed factors such as marriage, physical health and health distress have a positive relationship and factors like duration of disease, physical role limitations, and social stigma have a negative relationship with the quality of life of people with MS. The quality of life of people with MS is more influenced by mental and psychological factors than the physical limitations of these patients.


Subject(s)
Multiple Sclerosis , Humans , Multiple Sclerosis/psychology , Quality of Life , Social Stigma , Cross-Sectional Studies , Reproducibility of Results , Surveys and Questionnaires
9.
Iran J Nurs Midwifery Res ; 28(5): 487-503, 2023.
Article in English | MEDLINE | ID: mdl-37869688

ABSTRACT

Background: More than 30% of women experience at least one abortion. To date, there has been no comprehensive mobile health project on the impact of technology on access to abortion, contraception, and post-abortion follow-up. The purpose of this study was to review published studies on the role of electronic health in the prevention of unwanted pregnancy, abortion, and post-abortion follow-up. Materials and Methods: The Web of Science, PubMed, ScienceDirect, and EMBASE databases were searched to find relevant articles published between 2008 and 2018. A systematic review study was conducted on 33 relevant articles. All studies related to the use and impact of electronic health on unwanted pregnancy prevention, abortion and post-abortion follow-up in English from January 2008 to December 2018 were included. The quality of the studies was evaluated using the PRISMA-S. Results: Thirty-three studies met the inclusion criteria for the review. The Studies were divided into four main groups of women's experiences on the use of mobile health and telemedicine technologies for at-home medical abortion, unwanted pregnancy prevention, abortion, and post-abortion follow-up. The results showed the significant impact of using electronic health on unwanted pregnancy prevention, abortion, and post-abortion follow-up. Conclusions: Health technologies have the potential to be used as a low-cost and accessible method to replace abortion services. They can facilitate remote care and quick access to information to complete the gaps in access to abortion. Therefore, it is necessary for health service providers to be aware of the possibility of the client's access to electronic health tools.

10.
Am J Clin Exp Urol ; 11(4): 344-347, 2023.
Article in English | MEDLINE | ID: mdl-37645618

ABSTRACT

The most common histological type of urinary bladder cancer is urothelial carcinoma (UC). Clear cell adenocarcinoma (CCA) of the urinary bladder is a rare histologic subtype of adenocarcinoma in the urinary tract. The tumor primarily affects women and has histomorphological features resembling CCA of the female genital tract (or Müllerian origin). Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. Patients typically present with gross hematuria, dysuria, and discharge. In this study, we report a case of a 50-year-old male, presenting with gross hematuria, which was subsequently diagnosed with CCA at our pathology department. Furthermore, we provide a short systematic review of the literature for this rare histopathological entity and a brief discussion about its morphological and immunohistochemical (IHC) characteristics.

11.
J Educ Health Promot ; 12: 215, 2023.
Article in English | MEDLINE | ID: mdl-37545996

ABSTRACT

BACKGROUND: Improving the physical, psychological, and social factors in the elderly significantly increases the QoL1 among them. This study aims to identify the crucial factors for predicting QoL among the elderly using statistical methods. MATERIALS AND METHODS: In this study, 980 samples related to the elderly with favorable and unfavorable QoL were investigated. The elderly's QoL was investigated using a qualitative and self-assessment questionnaire that measured the QoL among them by five Likert spectrum and independent factors. The Chi-square test and eta coefficient were used to determine the relationship between each predicting factor of the elderly's QoL in SPSS V 25 software. Finally, we used the Enter and Forward LR methods to determine the correlation of influential factors in the presence of other variables. RESULTS: The study showed that 20 variables gained a significant relationship with the quality of life of the elderly at P < 0.05. The study results showed that the degree of dependence (P = 0.03), diabetes mellitus (P = 0.03), formal and informal social relationships (P = 0.01 and P = 0.02), ability to play an emotional role (P = 0.03), physical performance (P = 0.01), heart diseases and arterial blood pressure (P = 0.02), and cancer (P = 0.01) have favorable predictive power in predicting the QoL among the elderly. CONCLUSION: Attempts to identify and modify the important factors affecting the elderly's QoL have a significant role in improving the QoL and life satisfaction in this age group people. This study showed that the statistical methods have a pleasant capability to discover the factors associated with the elderly's QoL with high performance in this regard.

12.
Ann Med Surg (Lond) ; 85(7): 3599-3603, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37440956

ABSTRACT

The application of pterional approach via the extended lateral corridor (PAVEL) for aneurysms of the distal basilar artery has been associated with significant successes. However, this approach has been rarely used to manage multiple aneurysms in patients who are not candidates for endovascular intervention. Case presentation: A 58-year-old male patient was referred to our neurosurgical unit with severe headache, nausea and vomiting, and neck pain. The patient had a history of hypertension but no past surgical history. A computerized tomography scan showed subarachnoid hemorrhage in the basal cisterns. Also, three-dimensional cerebral vascular imaging revealed three aneurysms involving the left middle cerebral artery, the basilar artery apex, and the left superior cerebellar artery. Due to his comorbidities and the severity of his symptoms, an endovascular intervention was not possible. The patient underwent the PAVEL approach to clip these three aneurysms. Following surgery, the patient had temporary right-sided hemiparesis and left-side ptosis, which improved 3 months after surgery. Clinical discussion: In this article, we present a narrated video of the intraoperative management of the three aneurysms and discussed the benefit and likely complications of this procedure. Conclusion: The PAVEL approach provides a single approach for multiple anterior and posterior circulation aneurysms instead of multiple procedures, thus minimizing patient postsurgical morbidity and mortality.

13.
Digit Health ; 9: 20552076231178425, 2023.
Article in English | MEDLINE | ID: mdl-37284015

ABSTRACT

Objective: The aging phenomenon has an increasing trend worldwide which caused the emergence of the successful aging (SA)1 concept. It is believed that the SA prediction model can increase the quality of life (QoL)2 in the elderly by decreasing physical and mental problems and enhancing their social participation. Most previous studies noted that physical and mental disorders affected the QoL in the elderly but didn't pay much attention to the social factors in this respect. Our study aimed to build a prediction model for SA based on the physical, mental, and specially more social factors affecting SA. Methods: The 975 cases related to SA and non-SA of the elderly were investigated in this study. We used the univariate analysis to determine the best factors affecting the SA. AB3, XG-Boost J-48, RF4, artificial neural network5, support vector machine6, and NB7 algorithms were used for building the prediction models. To get the best model predicting the SA, we compared them using positive predictive value (PPV)8, negative predictive value (NPV)9, sensitivity, specificity, accuracy, F-measure, and area under the receiver operator characteristics curve (AUC). Results: Comparing the machine learning10 model's performance showed that the random forest (RF) model with PPV = 90.96%, NPV = 99.21%, sensitivity = 97.48%, specificity = 97.14%, accuracy = 97.05%, F-score = 97.31%, AUC = 0.975 is the best model for predicting the SA. Conclusions: Using prediction models can increase the QoL in the elderly and consequently reduce the economic cost for people and societies. The RF can be considered an optimal model for predicting SA in the elderly.

14.
Int J Soc Psychiatry ; 69(8): 1898-1908, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37326111

ABSTRACT

BACKGROUND: Among refugees residing in countries of first asylum, such as Malaysia, high rates of psychological distress call for creative intervention responses. AIMS: This study examines implementation of a Screening, Brief Intervention, and Referral to Treatment (SBIRT) model promoting emotional well-being and access to services. METHOD: The one-session intervention was implemented in community settings by refugee facilitators during 2017 to 2020. 140 Participants including Afghan (n = 43), Rohingya (n = 41), and Somali (n = 56) refugees were randomized to receive either the intervention at baseline, or to a waitlist control group. At 30 days post-intervention, all participants completed a post-assessment. Additionally, after completing the intervention, participants provided feedback on SBIRT content and process. RESULTS: Findings indicate the intervention was feasible to implement. Among the full sample, Refugee Health Screening-15 emotional distress scores reduced significantly among participants in the intervention group when compared to those in the waitlist control group. Examining findings by nationality, only Afghan and Rohingya participants in the intervention condition experienced significant reductions in distress scores compared to their counterparts in the control condition. Examining intervention effects on service access outcomes, only Somali participants in the intervention condition experienced significant increases in service access compared to the control condition. CONCLUSIONS: Findings indicate the potential value of this SBIRT intervention, warranting further research.


Subject(s)
Mental Health , Refugees , Humans , Refugees/psychology , Crisis Intervention , Malaysia , Feasibility Studies , Referral and Consultation
15.
Health Sci Rep ; 6(6): e1370, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37359406

ABSTRACT

Background and Aims: This study aimed to look at the influence of short-term dynamic psychotherapy on sexual function and marital satisfaction in women with depression. Methods: Through a clinical trial study using a pretest-posttest design and a control group, this study enlisted the participation of 60 women diagnosed with depression. The patients were interviewed before being randomly assigned to experimental or control groups. Data were obtained through the Beck Depression Inventory, the Enrique Marital Satisfaction Questionnaire, and the Female Sexual Function Questionnaire. The experimental group received intense short-term dynamic psychotherapy intervention, while the control group was on a 2-month waiting list. The SPSS 24 program utilized an analysis of variance to analyze the data. Results: The pre- and posttest study results revealed a significant difference in marital satisfaction, sexual function, and depression between the experimental and control groups (p < 0.01). Conclusion: During the posttest phase, a short-term intensive dynamic psychotherapy intervention helped the experimental group feel better about their marriage and improve their sexual function. It also helped them feel less depressed.

16.
J Gynecol Obstet Hum Reprod ; 52(4): 102568, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36868502

ABSTRACT

Since the PLAGL1 (ZAC1) gene is expressed in the human endometrium. It may be involved in the etiology of endometrial disorders by its abnormal regulation and expression. This study aimed to investigate the Zac1 gene and related microRNA and LncRNA and its alterations in patients with endometriosis. Blood plasma, ectopic (EC) and eutopic (EU) endometrial samples were gathered from 30 patients with endometriosis and 30 healthy fertile women, and the Q-PCR technique was used to determine the expression level of Zac1 mRNA and microRNAs (miR-1271-5p, hsa-miR-490-3pin) and LncRNAs (TONSL-AS1 TONSL, KCNQ1OT1 KCNQ1). According to the results, the Zac1 gene and KCNQ1OT1 KCNQ1, TONSL-AS1 TONSL LncRNA expression were significantly decreased in the endometriosis group versus the control group (P < 0.05). MiR-1271-5p and hsa-miR-490-3pin microRNA expression were significantly raised in the endometriosis group as opposed to the control group (P < 0.05). In summary, this research for the first time revealed that identifying Zac1 expression provides us with new indicators for evaluating endometriosis.


Subject(s)
Endometriosis , MicroRNAs , RNA, Long Noncoding , Humans , Female , Endometriosis/genetics , Endometriosis/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , KCNQ1 Potassium Channel , MicroRNAs/genetics , Biomarkers , Transcription Factors , Cell Cycle Proteins , Tumor Suppressor Proteins/metabolism , NF-kappa B/metabolism
17.
J Pharm Sci ; 112(4): 1000-1010, 2023 04.
Article in English | MEDLINE | ID: mdl-36642375

ABSTRACT

Monoclonal antibodies against tumor necrosis factor-alpha (TNFα) are widely used for treatment of inflammatory diseases. However, despite the inhibitory effect this class of drugs has on the immune system, anti-drug antibodies are often formed with continuous use. Particles formed during stress conditions, which can be used to simulate storage and handling conditions of commercial antibodies, have previously been associated with the formation of anti-drug antibodies. This study investigates the relationship between particles, oligomerization, folding and chemical degradation on the in vitro cytokine response toward the TNFα inhibitor adalimumab. Adalimumab aggregates generated using stir and heat stress were fractionated into distinct sub-populations, and their structure and immunogenic potential were evaluated. A chemically degraded sample of adalimumab was included to compare particle composition with the milder accelerated heat and stir stressed conditions. Particles from stressed adalimumab samples induced elevated cytokine levels and CD4+ T cell proliferation in vitro compared to non-stressed samples. Samples enriched with both submicron and subvisible particles of adalimumab induced the strongest cytokine release and the strongest CD4+ T cell proliferation despite maintaining some TNFα inhibitory functionality. Samples that were stressed and subsequently purified of subvisible and submicron particles did not elicit a significantly higher cytokine response or show increased CD4+ T cell proliferation compared to a non-stressed sample. Oxidation-induced chemical modifications in adalimumab, mainly in Met, His, Trp, and Tyr, were not found to be sufficient in absence of particle formation to induce increased CD4+ T cell proliferation or cytokine release despite less decreased TNFα inhibitory activity of adalimumab. These observations provide further evidence that particles do indeed potentiate the immunogenic potential of adalimumab.


Subject(s)
Antibodies, Monoclonal , Tumor Necrosis Factor-alpha , Adalimumab/pharmacology , Antibodies, Monoclonal/chemistry , Cytokines
18.
Biol Trace Elem Res ; 201(2): 559-566, 2023 Feb.
Article in English | MEDLINE | ID: mdl-35226276

ABSTRACT

Zinc is an essential microelement that plays many important functions in the body. It is crucial for the regulation of cell growth, hormone release, immunological response, and reproduction. Thus, this trial aimed to evaluate the effects of zinc supplementation in comparison with placebo on the improvement of premenstrual symptoms in female university students. This triple-masked, randomized, placebo-controlled, parallel trial was conducted among 69 female students aged 18-35 with premenstrual syndrome that living in dormitories of Hamadan University of Medical Sciences, in west of Iran. Participants were randomly assigned to two groups of equal number; one group received 220 mg of elemental zinc (n = 33) and the other group received placebo (n = 36) on a regular daily for 24 weeks. The premenstrual syndrome was assessed by Premenstrual Symptoms Screening Tool-Adolescent (PSST-A) questionnaire for all participants. Chi-square and t-student tests were used to compare the percentage or mean of parameters between two groups. All statistical analysis conducted by SPSS version 16. The mean age in the intervention group was 25.64 [Formula: see text] 0.53 years, and in the control group was 24.38 [Formula: see text] 0.51 years (P = 0.087). After 24 weeks of intervention, PMS physical and psychological symptoms such as anger, anxiety, depressed mood, overeating, breast tenderness, headaches, muscle pain, bloating, and weight gain significantly decreased in zinc group compared to placebo group (P < 0.001). We observed a significant increase in relationship with friends, classmates, and coworkers (p = 0.003) after 24 weeks of intervention with zinc compared to placebo. In conclusion, zinc, as a simple and inexpensive treatment, was associated with improvement of PMS symptoms. Given that this is among the first studies to evaluate the effect of zinc supplementation on PMS, additional studies are warranted to confirm these findings.


Subject(s)
Premenstrual Syndrome , Zinc , Adolescent , Female , Humans , Infant , Zinc/therapeutic use , Universities , Double-Blind Method , Premenstrual Syndrome/drug therapy , Students , Dietary Supplements
19.
World Neurosurg ; 170: e180-e187, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36328167

ABSTRACT

OBJECTIVE: Predicting meningioma consistency with preoperative imaging is critical for surgery planning. Preoperative T1 and T2-weighted and fluid attenuated inversion recovery magnetic resonance imaging (MRI) findings of supratentorial meningioma tumors were studied and compared with intraoperative supratentorial meningioma tumor consistency based on the Cavitron ultrasound surgical aspirator (CUSA) and ZADA grading scales in this cohort to predict the tumor consistency before surgery. METHODS: MRI from 78 consecutive patients who underwent supratentorial meningioma tumor resection between 2018 and 2021 were evaluated preoperatively. An intraoperative tumor consistency grade was applied to these lesions prospectively by the operating surgeon based on CUSA and ZADA grading scales. Tumor/cerebellar peduncle T2-weighted intensity, tumor/cerebellar peduncle T1-weighted intensity (TCT1I), and tumor/cerebellar peduncle fluid attenuated inversion recovery intensity (TCFI) ratios were calculated. Tumor consistency grades and MRI intensity ratios were correlated using one-way ANOVA. RESULTS: Of the 78 patients, 52 (66.7%) were female and 26 (33.3%) were male. Tumor volume correlated with tumor consistency grades on both CUSA (P = 0.005) and ZADA (P = 0.024) grading scales. Also patients age correlated with tumor consistency according to ZADA grading scale (P = 0.024). TCT1I (P = 0.009) and TCFI (P < 0.005) ratios correlated significantly with tumor consistency grade according to CUSA. Similarly, TCT1I (P = 0.0032) and TCFI (P = 0.001) ratios was significantly associated with tumor consistency according to ZADA grading scales. CONCLUSIONS: Our findings suggest that higher tumor/cerebellar peduncle T2-weighted intensity and TCFI ratios correlate with softer tumors, while higher TCT1I ratios reveal firmer tumors. These data can assist the surgeon predict the supratentorial meningioma consistency before surgery.


Subject(s)
Meningeal Neoplasms , Meningioma , Supratentorial Neoplasms , Humans , Male , Female , Meningioma/diagnostic imaging , Meningioma/surgery , Meningioma/pathology , Magnetic Resonance Imaging/methods , Cerebellum/pathology , Supratentorial Neoplasms/diagnostic imaging , Supratentorial Neoplasms/surgery , Meningeal Neoplasms/diagnostic imaging , Meningeal Neoplasms/surgery , Meningeal Neoplasms/pathology
20.
Nature ; 611(7935): 405-412, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36323780

ABSTRACT

Solid tumours are innervated by nerve fibres that arise from the autonomic and sensory peripheral nervous systems1-5. Whether the neo-innervation of tumours by pain-initiating sensory neurons affects cancer immunosurveillance remains unclear. Here we show that melanoma cells interact with nociceptor neurons, leading to increases in their neurite outgrowth, responsiveness to noxious ligands and neuropeptide release. Calcitonin gene-related peptide (CGRP)-one such nociceptor-produced neuropeptide-directly increases the exhaustion of cytotoxic CD8+ T cells, which limits their capacity to eliminate melanoma. Genetic ablation of the TRPV1 lineage, local pharmacological silencing of nociceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating leukocytes and decreased the growth of tumours, nearly tripling the survival rate of mice that were inoculated with B16F10 melanoma cells. Conversely, CD8+ T cell exhaustion was rescued in sensory-neuron-depleted mice that were treated with local recombinant CGRP. As compared with wild-type CD8+ T cells, Ramp1-/- CD8+ T cells were protected against exhaustion when co-transplanted into tumour-bearing Rag1-deficient mice. Single-cell RNA sequencing of biopsies from patients with melanoma revealed that intratumoral RAMP1-expressing CD8+ T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis. Overall, our results suggest that reducing the release of CGRP from tumour-innervating nociceptors could be a strategy to improve anti-tumour immunity by eliminating the immunomodulatory effects of CGRP on cytotoxic CD8+ T cells.


Subject(s)
CD8-Positive T-Lymphocytes , Melanoma , Nociceptors , Animals , Mice , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/pharmacology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/pathology , Melanoma/immunology , Melanoma/pathology , Nociceptors/physiology , Sensory Receptor Cells/metabolism , Neurites/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/pathology , Survival Rate , Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Genes, RAG-1/genetics , Humans , Biopsy , Prognosis
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