Hasil untuk "Therapeutics. Pharmacology"

Boyan Liu, Boyan Liu, Xufeng Liu et al.

BackgroundA growing body of research indicates that mechanobiology plays a pivotal role in cancer pathogenesis and holds considerable therapeutic potential. However, a comprehensive bibliometric analysis of this interdisciplinary field is lacking, partly due to challenges in cross-database data integration. In this study, we aim to construct a systematic knowledge map of cancer mechanobiology to delineate its research progress, core structure, and emerging trends.MethodsIn this study, we integrated 1,947 publications from the Web of Science (WoS) Core Collection and Scopus (1976–2025). To address cross-database heterogeneity, we developed a novel, customized, multi-stage data-standardization workflow combining a bespoke Python parsing engine with fuzzy string matching algorithms and manual verification. The unified dataset was analyzed using CiteSpace, VOSviewer, and Bibliometrix.ResultsThe United States and China are the most prolific countries, while the University of California system is the most productive institution. Valerie M. Weaver is the most published author, while Matthew J. Paszek is the most co-cited, indicating foundational influence. Cell is the most influential journal based on co-citation frequency. Keyword analysis reveals a thematic evolution from “extracellular matrix stiffness” and “mechanotransduction” to frontier areas such as “cancer immunotherapy” and “YAP signaling protein.”ConclusionIn this study, we construct a comprehensive bibliometric map of cancer mechanobiology. Our findings elucidate the developmental trajectory and research hotspots of the field, providing a data-driven reference for future investigations, international collaborations, and clinical translation of physical oncology.

Yang J, Xue X, Yang Z et al.

Jing Yang,1 Xiaoling Xue,2 Zhi Yang,1 Fei Hao,1 Bangtao Chen3 1Department of Dermatology, Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, People’s Republic of China; 2Department of Pathogenic Biology, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, 121001, People’s Republic of China; 3Department of Dermatology, Chongqing University Three Gorges Hospital, School of Medicine, Chongqing University, Chongqing, 404000, People’s Republic of ChinaCorrespondence: Fei Hao, Email 651588@hospital.cqmu.edu.cn Bangtao Chen, Email medisci@163.comObjective: To profile spinal medium- and long- chain fatty acids (ML-CFAs) and itch-related gene expressions (IRGEs) in dorsal root ganglion (DRG), and investigate the role of spinal palmitic acid (PA) in atopic dermatitis (AD), and its relationship with DRG and spinal extracellular signal-regulated kinase (ERK).Methods: MC903 was applied topically to the nape of C57BL/6 mice to induce AD. Two doses of PA were administered intrathecally during MC903 treatment, and several antagonists were administered intrathecally one day before PA challenge. Transcriptome sequencing was performed on DRGs, and 36 ML-CFAs in the spinal cord were analyzed.Results: A global upregulation of IRGEs in DRGs and increases in major ML-CFAs including PA in the spinal cord were observed in adult AD model. MC903 resulted in less severe dermatitis with weaker IRGEs in DRGs and lower spinal ML-CFAs in senile than adult mice. In adult mice, intrathecal PA injection caused acute scratches, aggravated AD, and induced stronger IRGEs in DRGs. Intrathecal injection of transient receptor potential vanilloid-1 channel (TRPV1) antagonist capsazepine or Mas-related G protein-coupled receptor D (MRGPRD) antagonist d-Pro7-ANG-(1-7) remarkably halted PA/MC903-induced dermatitis and PA-induced scratching. Administration of histamine h4 receptor antagonist JNJ7777120 only moderately alleviated dermatitis, with no notable effect on scratches. Intrathecal pan-palmitoylation inhibitor 2-Bromopalmitate moderately alleviated MC903/PA-induced lesions and spinal ERK phosphorylation. Intrathecal lidocaine markedly suppressed both lesions and ERK phosphorylation, along with a global reduction in IRGEs in DRGs. Finally, PA-induced scratches were significantly improved by intrathecal lidocaine but not 2-Bromopalmitate.Conclusion: MC903-induced AD develops more readily in adult than senile mice, with consistent changes in IRGEs in DRG and spinal ML-CFA levels, including PA. Spinal PA promotes AD involving spinal TRPV1 and MRGPRD signaling, and IRGEs increments in DRG. Intrathecal lidocaine suppresses AD aggravated by PA via inhibiting spinal ERK phosphorylation and reducing IRGEs in DRG.Keywords: Atopic dermatitis, Palmitic acid, Dorsal root ganglion, Spinal cord, Extracellular signal-regulated kinase, Transcriptome sequencing

Kunal Saxena, Amanda Dempsey, Rishi P. Verma et al.

This study explored attitudes/perceptions among parents who have not yet agreed to HPV vaccination for their 11–12-y-old children. US parents/guardians were recruited from a consumer panel for this online, cross-sectional survey. Parents (≥18 y) were eligible if their oldest child was 11–12, participated in their child’s vaccine decisions/visit, had not decided on, or would refuse the HPV vaccine, and understood English. Parents were excluded if their child had medical conditions affecting eligibility for HPV vaccination or if they declined to provide consent. Sampling quotas were used for parent and child age, sex, and US region. Of 200 participants, half were undecided whether to accept HPV vaccination for their children and half planned to refuse (purposely targeted recruitment). Most participants were women (70%) and White (86%) with a mean age of 39 y. Significantly, more parents who planned to refuse reported delaying/refusing other vaccinations compared to undecided parents (57% vs 11%, p < .001). Undecided parents selected significantly different primary reasons for not vaccinating (p < .001); they were more concerned about side effects (42% vs 25%) and less worried it would encourage their children to be sexually active (9% vs 22%). Most parents in the undecided cohort reported they would definitely have accepted the HPV vaccination (52% vs 36%) if their child’s provider had offered it when their child was younger, compared to parents who planned to refuse. Introducing HPV vaccine at an earlier age may be associated with increased parental acceptance specifically among those children who had not yet received HPV vaccination.

Ayesha Mudasser, Mubina Laghari, Aman Ullah Siddiqui et al.

Background: Salivary biomarkers are non-invasive molecules that indicate neurodegenerative illnesses, especially Alzheimer disease (AD) and Parkinson disease (PD).this study was conducted to determine the diagnostic precision of salivary proteomic and genomic biomarkers in terms of early AD and PD detection. Methods: A systematic literature search was conducted in PubMed, web of science and Google Scholar, and studies included from 2016 to 2025. Research that examined salivary biomarkers in AD and PD was eligible. The data were analyzed with a random-effects model and odds ratios (OR), standard mean differences (SMD), and 95% confidence interval (CI) was estimated. Also, subgroup and sensitivity analysis were performed. To assess the risk of bias, the Newcastle-Ottawa Scale (NOS) was applied for included observational studies. Results: A total of 11 eligible studies concerning proteomic biomarkers, including amyloid-β (Aβ42, Aβ40) and alpha-synuclein total (α-synTotal)  and alpha-synuclein Oligomer (α-synOligo), and genomic biomarkers like different salivary microRNAs were included. Meta-analysis indicated that Aβ42 (OR=0.70; 95% CI: 0.41 to 1.1) and Aβ40 (OR=1.01; 95% CI: 0.97 to 1.06) had significant discriminatory potential in AD patients; but α-synOligo (SMD = 2.90; 95% CI: -0.59–6.39) and α-synTotal (SMD = 0.44; 95% CI: -3.14 to 4.02) was higher in PD patients as compared with controls. Genomic biomarkers demonstrated inconsistent findings (SMD = -0.18; 95% CI: -1.79–1.42) because of difference in microRNA types. Heterogeneity was high (I2 > 90%), which is caused by alterations in study design and in the methods to measure biomarkers. Discussion: Salivary biomarkers were found to be an insignificant yet exceptional method of early examination of AD and PD. Nonetheless, the inconsistency of different studies points to develop standardized protocols.

Saleema Rehman, Humaira Bilqis, Farah Deeba et al.

Background: Morbidly adherent placenta (MAP) is one of the most dreaded antenatal complications leading to massive hemorrhage, immense blood transfusion, hysterectomy, intensive care unit admission, mechanical ventilation, multi-organ failure and maternal mortality. The study aimed to determine the maternal outcome in terms of complications, interventions, and mortality in patients with MAP in a tertiary care hospital. Methods: During the study period of one year (2020-2021) a total of 68 patients with MAP were studied. Demographic profiles including age, parity, gestational age and history of previous cesarean sections were recorded. Other complications and interventions were also noted. Data was analyzed by using SPSS version 23 and a t-test was applied for comparison between the two groups. p-value <0.05 was considered statistically significant. Results: Total number of deliveries during the study period was 20971. Among these 7183 women had a cesarian section (CS). The total number of CS done due to placenta previa was 319, out of which a total of 68(21.3%) patients were diagnosed with MAP. It was further observed that 0.6% of patients had no history of a previous uterine scar, 39.0% of patients with previous 1 scar and 80% with 4 scars (p>0.05). Peripartum hysterectomy was performed in 48.5% of patients. The complications noted were bladder injury 17.6%, ICU admission 45.5% and maternal mortality 4.4%. Conclusion: Morbidly adherent placenta (MAP) was found directly related to cesarean section (p>0.05). Appropriate measures should be taken to reduce the primary scars to reduce the incidence of repeat scars and ultimately MAP related severe maternal outcomes. Keywords: Morbidly Adherent Placenta (MAP); Caesarean Section; Placenta Previa.

Jyotsna Bhatt Mitra, Saurav Chatterjee, Anuj Kumar et al.

Abstract Background The urgent demand for innovative theranostic strategies to combat bacterial resistance to antibiotics is evident, with substantial implications for global health. Rapid diagnosis of life-threatening infections can expedite treatment, improving patient outcomes. Leveraging diagnostic modalities i.e., positron emission tomography (PET) and single photon emission computed tomography (SPECT) for detecting focal infections has yielded promising results. Augmenting the sensitivity of current PET and SPECT tracers could enable effective imaging of pathogenic bacteria, including drug-resistant strains.UBI (29–41), an antimicrobial peptide (AMP) fragment recognizes the S. aureus membrane through electrostatic binding. Radiolabeled UBI (29–41) is a promising SPECT and PET-based tracer for detecting focal infections. 2-APBA (2-acetyl-phenyl-boronic acid), a non-natural amino acid, specifically targets lysyl-phosphatidyl-glycerol (lysyl-PG) on the S. aureus membranes, particularly in AMP-resistant strains. We propose that combining UBI with 2-APBA could enhance the diagnostic potential of radiolabeled UBI. Results Present work aimed to compare the diagnostic potential of two radiolabeled peptides, namely UBI (29–41) and 2-APBA modified UBI (29–41), referred to as UBI and UBI-APBA. APBA modification imparted antibacterial activity to the initially non-bactericidal UBI against S. aureus by inducing a loss of membrane potential. The antibacterial activity demonstrated by UBI-APBA can be ascribed to the synergistic interaction of both UBI and UBI-APBA on the bacterial membrane. To enable PET imaging, we attached the chelator 1,4,7-triazacyclononane 1-glutaric acid 4,7-acetic acid (NODAGA) to the peptides for complexation with the positron emitter Gallium-68 (68Ga). Both NODAGA conjugates were radiolabeled with 68Ga with high radiochemical purity. The resultant 68Ga complexes were stable in phosphate-buffered saline and human serum. Uptake of these complexes was observed in S. aureus but not in mice splenocytes, indicating the selective nature of their interaction. Additionally, the APBA conjugate exhibited superior uptake in S. aureus while preserving the selectivity of the parent peptide. Furthermore, [68Ga]Ga-UBI-APBA demonstrated accumulation at the site of infection in rats, with an improved target-to-non-target ratio, as evidenced by ex-vivo biodistribution and PET imaging. Conclusions Our findings suggest that linking UBI, as well as AMPs in general, with APBA shows promise as a strategy to augment the theranostic potential of these molecules.

Zou Z, Li J, Ji X et al.

Zhonghua Zou,1 Jinping Li,2 Xiang Ji,2 Tingxing Wang,1 Qingqing Chen,1 Zhengcao Liu,1 Shengjun Ji1 1Department of Radiotherapy & Oncology, the Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, People’s Republic of China; 2Department of Gastroenterology, Fangzi People’s Hospital, Weifang, People’s Republic of ChinaCorrespondence: Shengjun Ji, Department of Radiotherapy & Oncology, the affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, No. 16 Baita Road, Suzhou, 215001, People’s Republic of China, Email drshengjunji@163.comBackground: The Naples Prognostic Score (NPS) can reflect patient’s nutritional and inflammatory status, which is identified as a prognostic indicator for various malignant tumors. However, its significance in patients with resected locally advanced non-small cell lung cancer (LA-NSCLC) patients who receive neoadjuvant treatment remains unclear so far.Methods: A total of 165 LA-NSCLC patients surgically treated from May 2012 to November 2017 were retrospectively investigated. The LA-NSCLC patients were divided into three groups according to NPS scores. The receiver operating curve (ROC) analysis was performed to reveal the discriminatory ability of NPS and other indicators for predicting the survival. The NPS and clinicopathological variables were further evaluated the prognostic value by univariate and multivariate Cox analysis.Results: The NPS was related to age (P = 0.046), smoking history (P = 0.004), Eastern Cooperative Oncology Group (ECOG) score (P = 0.005), and adjuvant treatment (P = 0.017). Patients with high NPS scores had worse overall survival (OS) (group 1 vs 0, P = 0.006; group 2 vs 0, P < 0.001) and disease-free survival (DFS) (group 1 vs 0, P < 0.001; group 2 vs 0, P < 0.001). The ROC analysis demonstrated that NPS had better predictive ability than other prognostic indicators. Multivariate analysis revealed that NPS was independent prognostic indicator of OS (group 1 vs 0, hazard ratio [HR] =2.591, P = 0.023; group 2 vs 0, HR = 8.744, P = 0.001) and DFS (group 1 vs 0, HR =3.754, P < 0.001; group 2 vs 0, HR = 9.673, P < 0.001).Conclusion: The NPS could be an independent prognostic indicator in patients with resected LA-NSCLC receiving neoadjuvant treatment and more reliable than the other nutritional and inflammatory indicators.Keywords: surgery, locally advanced NSCLC, NPS, prognosis, neoadjuvant treatment

Qing Chen, Xiaowei Zhang, Qicai Hu et al.

Abstract Background Chronic endometritis (CE) is a disease of continuous and subtle inflammation occurring in the endometrial stromal area, which is often asymptomatic or present with non-specific clinical symptoms. Methods This study investigated the composition and distribution of the intrauterine microbiota of 71 patients who underwent hysteroscopy during the routine clinical inspection of infertility. Among them, patients who were diagnosed with chronic endometritis (CE) were allocated into CE group (n = 29) and others into non-CE group (n = 42). There was no significant difference in average age between the two groups (P = 0.19). Uterine flushing fluid was collected by the self-developed cervical trocar uterine cavity sampler and 16S rRNA sequencing was performed. Results The alpha diversity in the CE group was significantly higher than that in the non-CE group (P < 0.05). Firmicutes (newly named Bacillota) were the dominant phylum in the non-CE group (72.23%), while their abundance was much lower in the CE group (49.92%), but there was no statistically significant difference between the two groups. The abundances of Actinobacteriota and Cyanobacteria in the CE group were significantly higher than those in the non-CE group (P < 0.05). At the genus level, the abundance of Lactobacillus dominated in all samples, which presented a significantly lower abundance in the CE group (40.88%) than that in the non-CE group (64.22%) (P < 0.05). Correspondingly, the abundance of non-Lactobacillus was higher in the CE group, among which Pseudomonas and Cutibacterium increased significantly (P < 0.01). Moreover, compared with the non-CE group, the pathways involved in arginine and proline metabolism and retinol metabolism were significantly enriched in the CE group (P < 0.05), while the metabolism of lipid and prenyltransferases were significantly decreased in the CE group (P < 0.05). Conclusions A certain microbial community was colonized in the uterine cavity, which was dominated by Lactobacillus. The structure and distribution of intrauterine microbiota in the CE group were different from those in the non-CE group by showing a lower abundance of Lactobacillus, and a significantly higher abundance of Pseudomonas and Cutibacterium. Additionally, the microbial metabolism was altered in the CE group. This study elaborated the alteration of intrauterine microbiota in CE patients, which may contribute to the diagnosis of CE and provide a reference for antibiotic treatment of CE.

Yan-Jie Qu, Min-Rui Ding, Chao Gu et al.

Context Ursolic acid (UA) and acteoside (ATS) are important active components that have been used to treat Alzheimer’s disease (AD) because of their neuroprotective effects, but the exact mechanism is still unclear.Objective Network pharmacology was used to explore the mechanism of UA + ATS in treating AD, and cell experiments were used to verify the mechanism.Materials and methods UA + ATS targets and AD-related genes were retrieved from TCMSP, STITCH, SwissTargetPrediction, GeneCards, DisGeNET and GEO. Key targets were obtained by constructing protein interaction network through STRING. The neuroprotective effects of UA + ATS were verified in H2O2-treated PC12 cells. The subsequent experiments were divided into Normal, Model (H2O2 pre-treatment for 4 h), Control (H2O2+ solvent pre-treatment), UA (5 μM), ATS (40 μM), UA (5 μM) + ATS (40 μM). Then apoptosis, mitochondrial membrane potential, caspase-3 activity, ATG5, Beclin-1 protein expression and Akt, mTOR phosphorylation levels were detected.Results The key targets of UA + ATS-AD network were mainly enriched in Akt/mTOR pathway. Cell experiments showed that UA (ED50: 5 μM) + ATS (ED50: 40 μM) could protect H2O2-induced (IC50: 250 μM) nerve damage by enhancing cells viability, combating apoptosis, restoring MMP, reducing the activation of caspase-3, lessening the phosphorylation of Akt and mTOR, and increasing the expression of ATG5 and Beclin-1.Conclusions ATS and UA regulates multiple targets, bioprocesses and signal pathways against AD pathogenesis. ATS and UA synergistically protects H2O2-induced neurotrosis by regulation of AKT/mTOR signalling.

O. I. Koniaieva, O. V. Matvieiev

In this article authors analyze patterns of ADRs registered in Crimea Republic in 2013. Data of ADR-reporting forms sent in 2013 by Crimean 21 doctors to Regional office of pharmacovigilance used. Information was recorded in local electronic database called “ARCADe”. 1129 reports from 89 clinics had been analyzed. Most frequently ADRs were found in patients from 46 to 60 years old (22%) and in first year babies (8%). Among adults females suffered from MP ADRs more than males (61%), but among children boys dominated (58%). Most frequent type of serious ADR (37%) was life-threating ones and those, which led to hospitalization. Two reports informed about lethal reactions caused by Ceftriaxone and combination “Pitofenon+Metamizole-sodium”. Causalityassessment revealed that bigger part of ADRs had belonged to “probable” type(43%). During risk factors analysis, we found complicated allergy anamnesis(10%) and polypharmacy (5% of cases). In 22% and 17% of reports, suspended MPswere prescribed for respiratory diseases and cardiologic pathologies treatment(respectively), and in 10% of cases for therapy of infections. Leading clinicalpresentation of ADR was skin rashes with different manifestations, severityand localization (50%), symptoms of involvement of CNS (11%), GIT and bloodcirculation system (7% both) were registered less frequently. In 5% of reports, wefound descri ption of angioneurotic edema and in 1% - symptoms of anaphylacticshock. 68% of ADRs required additional prescri ption of drugs for correctionof reaction`s symptoms. 39% of ADRs were caused by systemic antimicrobialproducts, 13% and 11% by MP influencing on functions of heart and CNS(respectively). In antibiotics group Cephalosporins prevailed and Ceftriaxonecaused most of ADRs, “Zidovudine+Lamivudine” combination was leading inantiretroviral drugs, among cardiological drugs ACE inhibitors prevailed butleading drug was Amplodi pine, and among NSAIDs most reactions were causedby Metamizole-sodium and its combinations. Conclusions. In 2013, the patterns ofADRs in Crimea region did not change and were the same as in previous years.Pharmacovigilance activity is high and amount of received reports satisfies WHOrequirements. Found patterns will ease formation of local and national strategyfor prevention of ADRs

Kyle Vader, Perri R. Tutelman, Delane Linkiewich et al.

Background Patient engagement (PE) in research refers to partnering with people with lived experience (e.g., patients, caregivers, family) as collaborators in the research process. Although PE is increasingly being recognized as an important aspect of health research, the current state of PE among pain research trainees in Canada is unclear.Aims The aims of this study were to describe perspectives about and experiences with PE among trainees conducting pain research in Canada, to identify perceived barriers and facilitators, and to describe recommendations to improve its implementation.Methods A cross-sectional web-based survey (English and French) was administered to trainees at any level conducting pain research at any Canadian academic institution.Results A total of 128 responses were received; 115 responses were complete and included in the final analysis. The majority of respondents identified as women (90/115; 78.3%), in graduate school (83/115; 72.2%), and conducting clinical pain research (83/115; 72.2%). Most respondents (103/115; 89.6%) indicated that PE is “very” or “extremely” important. Despite this, only a minority of respondents (23/111; 20.7%) indicated that they “often” or “always” implement PE within their own research. The most common barrier identified was lack of knowledge regarding the practical implementation of PE, and understanding its positive value was the most commonly reported facilitator. Recommendations for improving the implementation of PE were diverse.Conclusions Despite viewing PE as important in research, a minority of pain research trainees regularly implement PE. Results highlight perceived barriers and facilitators to PE and provide insight to inform the development of future training and other enabling initiatives.

Müller T

Thomas M&uuml;ller Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, 13088, GermanyCorrespondence: Thomas M&uuml;llerDepartment of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, Berlin, 13088, GermanyTel +49 30 92790223Fax +49 30 92790703Email th.mueller@alexianer.deAbstract: Parkinson&rsquo;s disease (PD) is the second most chronic neurodegenerative disorder worldwide. Deficit of monoamines, particularly dopamine, causes an individually varying compilation of motor and non-motor features. Constraint of presynaptic uptake extends monoamine stay in the synaptic cleft. This review discusses possible benefits of dopamine reuptake inhibition for the treatment of PD. Translation of this pharmacologic principle into positive clinical study results failed to date. Past clinical trial designs did not consider a mandatory, concomitant stable inhibition of glial monoamine turnover, i.e. with monoamine oxidase B inhibitors. These studies focused on improvement of motor behavior and levodopa associated motor complications, which are fluctuations of motor and non-motor behavior. Future clinical investigations in early, levodopa- and dopamine agonist na&iuml;ve patients shall also aim on alleviation of non-motor symptoms, like fatigue, apathy or cognitive slowing. Oral levodopa/dopa decarboxylase inhibitor application is inevitably necessary with advance of PD. Monoamine reuptake (MRT) inhibition improves the efficacy of levodopa, the blood brain barrier crossing metabolic precursor of dopamine. The pulsatile brain delivery pattern of orally administered levodopa containing formulations results in synaptic dopamine variability. Ups and downs of dopamine counteract the physiologic principle of continuous neurotransmission, particularly in nigrostriatal, respectively mesocorticolimbic pathways, both of which regulate motor respectively non-motor behavior. Thus synaptic dopamine pulsatility overwhelms the existing buffering capacity. Onset of motor and non-motor complications occurs. Future MRT inhibitor studies shall focus on a stabilizing and preventive effect on levodopa related fluctuations of motor and non-motor behavior. Their long-term study designs in advanced levodopa treated patients shall allow a cautious adaptation of oral l-dopa therapy combined with a mandatory inhibition of glial monoamine turnover. Then the evidence for a preventive and beneficial, symptomatic effect of MRT inhibition on motor and non-motor complications will become more likely.Keywords: dopamine reuptake, monoamines, monoamine reuptake inhibition, Parkinson&rsquo;s disease; PD

Joanna Kochman, Karolina Jakubczyk, Piotr Bargiel et al.

Thyroid diseases, including neoplasms, autoimmune diseases and thyroid dysfunctions, are becoming a serious social problem with rapidly increasing prevalence. The latter is increasingly linked to oxidative stress. There are many methods for determining the biomarkers of oxidative stress, making it possible to evaluate the oxidative profile in patients with thyroid diseases compared to the healthy population. This opens up a new perspective for investigating the role of elevated parameters of oxidative stress and damage in people with thyroid diseases, especially of neoplastic nature. An imbalance between oxidants and antioxidants is observed at different stages and in different types of thyroid diseases. The organ, which is part of the endocrine system, uses free radicals (reactive oxygen species, ROS) to produce hormones. Thyroid cells release enzymes that catalyse ROS generation; therefore, a key role is played by the internal defence system and non-enzymatic antioxidants that counteract excess ROS not utilised to produce thyroid hormones, acting as a buffer to neutralise free radicals and ensure whole-body homeostasis. An excess of free radicals causes structural cell damage, undermining genomic stability. Looking at the negative effects of ROS accumulation, oxidative stress appears to be implicated in both the initiation and progression of carcinogenesis. The aim of this review is to investigate the oxidation background of thyroid diseases and to summarise the links between redox imbalance and thyroid dysfunction and disease.

Joanna Hajduk, Cyrill Brunner, Sebastian Malik et al.

Minor changes in the quality of biologically manufactured monoclonal antibodies (mAbs) can affect their bioactivity and efficacy. One of the most important variations concerns the N-glycosylation pattern, which directly affects an anti-tumor mechanism called antibody-dependent cell-meditated cytotoxicity (ADCC). Thus, careful engineering of mAbs is expected to enhance both protein-receptor binding and ADCC. The specific aim of this study is to evaluate the influence of terminal carbohydrates within the Fc region on the interaction with the FcγRIIIa/CD16a receptor in native and label-free conditions. The single mAb molecule comprises variants with minimal and maximal galactosylation, as well as α2,3 and α2,6-sialic acid isomers. Here, we apply native electrospray ionization mass spectrometry to determine the solution-phase antibody-receptor equilibria and by using temperature-controlled nanoelectrospray, a thermal stability of the complex is examined. Based on these, we prove that the galactosylation of a fucosylated Fc region increases the binding to CD16a 1.5-fold when compared with the non-galactosylated variant. The α2,6-sialylation has no significant effect on the binding, whereas the α2,3-sialylation decreases it 1.72-fold. In line with expectation, the galactoslylated and α2,6-sialylated mAb:CD16a complex exhibit higher thermal stability when measured in the temperature gradient from 20 to 50°C. The similar binding pattern is observed based on surface plasmon resonance analysis and immunofluorescence staining using natural killer cells. The results of our study provide new insight into N-glycosylation-based interaction of the mAb:CD16a complex.

Nina Vodošek Hojs, Sebastjan Bevc, Robert Ekart et al.

Diabetes prevalence is increasing worldwide, especially through the increase of type 2 diabetes. Diabetic nephropathy occurs in up to 40% of diabetic patients and is the leading cause of end-stage renal disease. Various factors affect the development and progression of diabetic nephropathy. Hyperglycaemia increases free radical production, resulting in oxidative stress, which plays an important role in the pathogenesis of diabetic nephropathy. Free radicals have a short half-life and are difficult to measure. In contrast, oxidation products, including lipid peroxidation, protein oxidation, and nucleic acid oxidation, have longer lifetimes and are used to evaluate oxidative stress. In recent years, different oxidative stress biomarkers associated with diabetic nephropathy have been found. This review summarises current evidence of oxidative stress biomarkers in patients with diabetic nephropathy. Although some of them are promising, they cannot replace currently used clinical biomarkers (eGFR, proteinuria) in the development and progression of diabetic nephropathy.

Kranti Suresh Vora, Aarthi Sundararajan, Shahin Saiyed et al.

The COVID-19 pandemic has imposed unprecedented health and socioeconomic challenges on public health, disrupting it on a global scale. Given that women and children are widely considered the most vulnerable in the times of emergency, whether in war or during a pandemic, the current pandemic has also severely disrupted access to reproductive and child health services. Despite this, data on the effect of the pandemic on pregnant women and newborns remain scarce, and gender-disaggregated indicators of mortality and morbidity are not available. In this context, we suggest the implementation of a gendered approach to ensure the specific needs of women and their newborns are considered during the development of COVID-19 vaccines. Taking into account gender-based biological differences, the inclusion of pregnant and lactating mothers in clinical trials for the development of COVID-19 vaccines is of vital importance.

Rouba Shaker, Danielle Fayad, Ghassan Dbaibo

Meningococcal disease continues to be a life threatening infection with high morbidity and mortality even in appropriately treated patients. Meningococcal vaccination plays a major role in the control of the disease; however, implementing vaccination remains problematic in the developing world. The objective of this review is to identify the challenges facing the use of meningococcal vaccines in the developing world in order to discuss the opportunities and available solutions to improve immunization in these countries. Inadequate epidemiologic information necessary to implement vaccination and financial challenges predominate. Multiple measures are needed to achieve the successful implementation of meningococcal conjugate vaccination programs that protect against circulating serogroups in developing countries including enhanced surveillance systems, financial support and aid through grants, product development partnerships that are the end result of effective collaboration and communication between different interdependent stakeholders to develop affordable vaccines, and demonstration of the cost-effectiveness of new meningococcal vaccines.

M. Nyalambisa, I.A. Oyemitan, R. Matewu et al.

Echinacea is used ethnomedicinally for the treatment of various diseases such as cough, respiratory infections, and bronchitis among other uses in Eastern Cape region of South Africa. This study evaluated the volatile components of the essential oil of the plant, its toxicity, anti-inflammatory and analgesic activities in rodents. Dried leaf and root of the plant were separately processed by hydrodistillation for 4 h and their essential oils (EOs) were collected. Extracted oils were subjected to GC/GC–MS analysis. The essential oil was further evaluated for acute toxicity, anti-inflammatory and analgesic activities. The toxicity profile of the essential oil was evaluated in mice through the oral route (p.o.), and anti-inflammatory activity was evaluated on the carrageenan-induced edema model in rats at the doses of 100–200 mg/kg, while its analgesic effect was evaluated on the acetic acid-induced writhings model in mice at doses of 100–200 mg/kg. GC/GC–MS analysis of EOs showed that a number of compounds identified in the leaf and root oils were 25 and 31 respectively. The chemical compositions of the oils varied and the major compounds identified in the oils include germacrene D, naphthalene, caryophyllene oxide, α-phellandrene and α-cadinol. The essential root oil did not cause mortality at the highest dose of 5000 mg/kg; hence, its LD50 was estimated to be ⩾5000 mg/kg, p.o. The anti-inflammatory test results showed that the essential root oil caused significant (p < 0.05–0.01) reduction in edema size compared to the negative control group on the carrageenan-induced edema and the results for the analgesic test showed that the essential root oil caused significant (p < 0.05) reduction in number of writhings at 1000 mg/kg compared to the negative control group. It is concluded that root and leaf of this Echinacea species contain volatile oils which varied in their yield and chemical compositions. The essential root oil is non-toxic orally and it demonstrated significant anti-inflammatory and analgesic activities in laboratory animals.

Ulfa Fauzia, Elsa P. Setiawati, Emma S. Surahman

Patient waiting time for healthcare services is identified by the World Health Organization (WHO) as one of the key measurements of a responsive health system. Waiting time for filing prescription can influence patient satisfaction on hospital pharmacy service. This study was conducted to analyze current condition of waiting time for filing precription and related parameters. This study was prospective cross-sectional study conducted for 10 days at a hospital pharmacy, in Indramayu, Indonesia. Data regarding distribution of patients flow was obtained. Statistical analysis was performed using Kolmogorov-Smirnov. We observed that this hospital uses single queue channel-single phase model in three counters, i.e., public health insurance (PHI), private/general, government insurance (GI). The rate of patients visit was (λ) 9.40 and the rate of service was (µ) 1.26 in PHI. In private/general counter, the rate of patients visit was (λ) 5.03 and the rate of service was (µ) 4.08. The rate of patients visit was (λ) 4.85 and the rate of service was (µ) 5.85 in GI. Data indicated that there was excessive work loads. Thus, several strategies should be performed to decrease waiting time, e.g., the use of computer-based queuing system and the improvement of quality and quantity of human resources in the hospital pharmacy. Keywords: waiting time, outpatient, queueing theory

G. Scoppettuolo, L. Dolcetti, A. Emoli et al.