bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Sciences Students’ Attitude, Perception, and Experience of Using Educational Simulation in Saudi Arabia: A Cross-Sectional Study
Authors: AlBalawi Ibrahim , Alqahtani Jaber S. , Al Ghamdi Shouq S. , Aldhahir Abdulelah M. , Alnasser Musallam , Alqahtani Abdullah S. , AlRabeeah Saad M. , Alkhathami Mohammed , Almaqati Thekra N. , AlDraiwiesh Ibrahim A. , Al Onezei Ameera K. , Jebakumar Arulanantham Zechariah , Alzahrani Yahya A. , Oyelade Tope , Alzahrani Eidan M.
Published: August 2022

Background: Simulation-based education (SBE) provides a safe, effective, and stimulating environment for training medical and healthcare students. This is especially valuable for skills that cannot be practiced on real patients due to ethical and practical reasons. We aimed to assess medical students’ attitude, perception, and experience of simulation-based medical education in Saudi Arabia. Method: A validated cross-sectional survey, using the KidSIM scale, was conducted to measure the level of perception and experience of students from different health sciences specialties toward integrating simulation as an educational tool. Participants responded to questions investigated the importance of simulation, opportunities for Inter-Professional Education (IPE), communication, roles and responsibilities, and situation awareness. Only students with previous experience of SBE were considered for participation. Result: This survey was completed by 246 participants, of whom 165 (67%) were male students and 228 (93%) were aged between the range of 18–30 years old. Of the respondents, 104 (67%) were respiratory care students, 90 (37%) were anesthesia technology students, and 45 (18%) were nursing students. Most of the participants had previous experience in IPE simulation activities (84%), and more than half of the students (54%) had a grade point average (GPA) ranging between 5.00 and 4.50. Overall, students had positive attitudes toward and beliefs about SBE, with a mean score of 129.76 ± 14.27, on the KidSIM scale, out of 150. Students’ GPA was significantly associated with a better perception to the relevance of simulation (p = 0.005), communication (p = 0.003), roles and responsibilities (p = 0.04), and situation awareness (p = 0.009). GPA is merely the sole predictor for positive attitude toward simulation with coefficient Beta value of 4.285 (p = 0.001). There were no significant correlations between other students’ characteristic variables (gender, specialty, study year, experience in IPE, and prior critical care experience). Conclusion: We found that health sciences students’ perception of SBE in Saudi Arabia is generally positive, and students’ performance is a significant determinant of the positive perception.
Taenia multiceps in Northern Tanzania: An Important but Preventable Disease Problem in Pastoral and Agropastoral Farming Systems
Authors: Kibona Tito , Buza Joram , Shirima Gabriel , Lankester Felix , Nzalawahe Jahashi , Lukambagire Abdul-Hamid , Kreppel Katharina , Hughes Ellen , Allan Kathryn J. , Cleaveland Sarah
Published: August 2022

Coenurosis due to Taenia multiceps has emerged as a major concern to small ruminant-owning communities in northern Tanzania. Although a high incidence of disease has been reported, gaps still remain in our knowledge of the disease problem across different agro-ecological settings. The study aimed to determine the prevalence of coenurosis in small ruminants and taeniid infection in dogs and identify risk factors for infection. Questionnaire surveys, postmortem examination of small ruminants, and coproscopic examination of dog faeces were used to collect data on reported coenurosis cases and taeniid infections, respectively. The twelve-month period prevalence of coenurosis in small ruminants was 8.4% (95% CI 8.2–8.6). The prevalence of taeniid infection in dogs was 12.5% (95% CI 9.1–17.4). The village-level prevalence of coenurosis in sheep and goats was significantly correlated with taeniid infection prevalence in dogs (r = 0.51, p = 0.029). Multivariable analysis indicated that home slaughter was significantly associated with the livestock owner-reported neurological syndrome due to coenurosis in sheep and goats (OR = 13.3, 95% CI 4.2–42.0, p < 0.001) and the practice of offering discarded brains to dogs was significantly associated with taeniid infection prevalence in dogs (OR = 2.80, 95% CI 0.98–7.98, p = 0.05). Coenurosis is a major disease problem in livestock-keeping communities of northern Tanzania, but there is little awareness of transmission risks associated with home slaughter and dog feeding practices. There is a need for veterinary and animal health services to engage more actively with communities to increase awareness of the transmission cycle of T. multiceps and the preventive measures that can be taken to reduce the impact of disease in livestock-dependent communities.
Microbiota Transplantation in Day-Old Broiler Chickens Ameliorates Necrotic Enteritis via Modulation of the Intestinal Microbiota and Host Immune Responses
Authors: Zaytsoff Sarah J. M. , Montina Tony , Boras Valerie F. , Brassard Julie , Moote Paul E. , Uwiera Richard R. E. , Inglis G. Douglas
Published: August 2022

A microbiota transplant (MT) originating from mature adult chicken ceca and propagated in bioreactors was administered to day-old broiler chicks to ascertain the degree to which, and how, the MT affects Clostridium perfringens (Cp)-incited necrotic enteritis (NE). Using a stress predisposition model of NE, birds administered the MT and challenged with Cp showed fewer necrotic lesions, and exhibited a substantially higher α- and β-diversity of bacteria in their jejunum and ceca. Birds challenged with Cp and not administered the MT showed decreased Lactobacillus and increased Clostridium sensu strico 1 in the jejunum. In ceca, Megamonas, a genus containing butyrate-producing bacteria, was only present in birds administered the MT, and densities of this genus were increased in birds challenged with Cp. Metabolite profiles in cecal digesta were altered in birds administered the MT and challenged with the pathogen; 59 metabolites were differentially abundant following MT treatment, and the relative levels of short chain fatty acids, butyrate, valerate, and propionate, were decreased in birds with NE. Birds administered the MT and challenged with Cp showed evidence of enhanced restoration of intestinal barrier functions, including elevated mRNA of MUC2B, MUC13, and TJP1. Likewise, birds administered the MT exhibited higher mRNA of IL2, IL17A, and IL22 at 2-days post-inoculation with Cp, indicating that these birds were better immunologically equipped to respond to pathogen challenge. Collectively, study findings demonstrated that administering a MT containing a diverse mixture of microorganisms to day-old birds ameliorated NE in broilers by increasing bacterial diversity and promoting positive immune responses.
Investigation of Rickettsia conorii in Patients Suspected of Having Crimean-Congo Hemorrhagic Fever
Authors: Baseri Neda , Salehi-Vaziri Mostafa , Mostafavi Ehsan , Bagheri Amiri Fahimeh , Latifian Mina , Stenos John , Esmaeili Saber
Published: August 2022

Rickettsia conorii is the causative agent of Mediterranean spotted fever (MSF). Misdiagnosis of MSF may occur with febrile syndromes associated with rash and thrombocytopenia, such as Crimean-Congo hemorrhagic fever (CCHF). This study aimed to determine the prevalence of R. conorii among serum samples obtained from 260 suspected CCHF patients with features of MSF in Iran (2018–2020). The quantitative polymerase chain reaction (qPCR) method detected three (1.15%) positive 16S rDNA Rickettsia spp. samples that were classified as R. conorii subsp. conorii, R. conorii subsp. Israelensis, and R. helvetica using the sequencing of gltA, ompA, and 17kDa genes. Furthermore, R. conorii IgM antibodies presented in 38 (14.62%) patients by the enzyme-linked immunosorbent assay (ELISA) method. Out of 97 MSF patients with available paired serum samples, IgM seroconversion and a four-fold increase were observed in 14 (14.43%) and 12 (12.37%) patients, respectively. We concluded that rickettsial agents are present in Iran and may be misdiagnosed with other febrile syndromes.
Demographics, Radiological Findings, and Clinical Outcomes of Klebsiella pneumonia vs. Non-Klebsiella pneumoniae Pyogenic Liver Abscess: A Systematic Review and Meta-Analysis with Trial Sequential Analysis
Authors: Chan Kai Siang , Chia Christopher Tze Wei , Shelat Vishal G.
Published: August 2022

Pyogenic liver abscess (PLA) is a common cause of hepatobiliary sepsis. Klebsiella pneumoniae (KP) is the most common organism causing PLA. Evidence is scarce on the demographics, radiological findings, and outcomes of KPPLA versus non-KPPLA (N-KPPLA). PubMed, Embase, The Cochrane Library, and Scopus were systematically searched until 14 May 2022 for studies comparing KPPLA and N-KPPLA. Exclusion criteria were single-arm studies. Primary outcomes were mortality (30-day/in-hospital) and metastatic complications. There were 16 studies, including 5127 patients (KPPLA n = 3305, N-KPPLA n = 1822). Patients with KPPLA were younger (mean difference: −2.04 years, p = 0.02). History of hepatobiliary disease (Odds ratio (OR) 0.30, 95% CI: 0.20, 0.46) and malignancy (OR 0.26, 95% CI: 0.16, 0.42) were less common in KPPLA. KPPLA was associated with lower incidence of multiple abscesses (OR 0.52, 95% CI: 0.35, 0.76, p < 0.001) and bilobar abscesses (OR 0.60, 95% CI: 0.49, 0.74, p < 0.001). KPPLA has higher overall metastatic complications (KPPLA 9.7% vs. N-KPPLA 4.8%, OR 3.16, 95% CI: 2.00, 4.99, p < 0.001), but lower mortality (KPPLA 3.9% vs. N-KPPLA 7.6%, OR 0.51, 95% CI: 0.34, 0.78, p < 0.001). Trial sequential analysis showed conclusive evidence that KPPLA has lower mortality than N-KPPLA. In conclusion, KPPLA has lower mortality than N-KPPLA.
Molecular Characterization of Methicillin-Sensitive Staphylococcus aureus from the Intestinal Tracts of Adult Patients in China
Authors: Li Yang , Tang Yuanyue , Jiang Zhongyi , Wang Zhenyu , Li Qiuchun , Jiao Xinan
Published: August 2022

Intestinal infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) have posed a great challenge for clinical treatments. In recent years, the intestinal carriage rates of MSSA have risen steadily in hospital settings in China. However, the epidemiology and molecular characteristics of MSSA from the intestinal tracts of Chinese adult patients remain unknown. In the present study, a total of 80 S. aureus isolates, including 64 MSSA and 16 methicillin-resistant Staphylococcus aureus (MRSA), were recovered from 466 fecal swabs in adult patients between 2019 and 2021 in China. The MSSA isolates exhibited high resistance to penicillin (92.2%) and erythromycin (45.3%). In addition, a higher proportion of MSSA isolates (14.1%) were multidrug-resistant (MDR) strains than that of MRSA isolates (1.3%). Among the 64 MSSA isolates, we identified 17 MLST types, of which ST398 and ST15 were the most predominant types. The most frequently detected resistance genes were blaZ (87.5%) and erm(C) (21.9%). The hemolysin genes (hla, hld, hlgA, hlgB, hlgC) were detected in all the MSSA isolates, but the Panton–Valentine leucocidin (pvl) gene was identified in 1.7% of the MSSA isolates. Our findings indicated that the prevalence and antimicrobial resistance of intestinal MSSA was a serious concern among adult patients in China.
Mycobacterium tuberculosis Rv2387 Facilitates Mycobacterial Survival by Silencing TLR2/p38/JNK Signaling
Authors: Li Wu , Deng Wanyan , Zhang Nan , Peng Huijuan , Xu Yi
Published: August 2022

Mycobacterium tuberculosis (Mtb) can evade antimicrobial immunity and persist within macrophages by interfering with multiple host cellular functions through its virulence factors, causing latent tuberculosis. The Rv2387 protein has been identified as a putative effector that potentially participates in Mtb pathogenicity. To explore the role of the Rv2387 protein in host–mycobacteria interactions, we established recombinant M. smegmatis strains and RAW264.7 cell lines that stably express the Rv2387 protein. We found that this protein suppresses mycobacteria infection-induced macrophage apoptosis by inactivating caspase-3/-8, thus facilitating the intracellular survival of mycobacteria. In addition, Rv2387 inhibits the production of inflammatory cytokines in macrophages by specifically suppressing TLR2-dependent stimulation of p38 and JNK MAPK pathways. Moreover, we further determined that the Rv2387 protein conferred a growth advantage over recombinant M. smegmatis and suppressed the inflammatory response in a mouse infection model. Overall, these data suggested that Rv2387 facilitates mycobacteria to escape host immunity and might be an essential virulence factor in Mtb.
Increased Levels of C5a in Gingival Crevicular Fluid and Saliva of Patients with Periodontal Disease
Authors: Bhalla Simran Preet , Shaju Ann Maria , Figueredo Carlos Marcelo da Silva , Miranda Leticia Algarves
Published: August 2022

C5a is a powerful complement effector molecule that is considered to be an important proinflammatory mediator in several systemic chronic inflammatory diseases. However, its levels in periodontal diseases are yet to be assessed. We aimed to analyse the secretion of C5a in gingival crevicular fluid (GCF) and saliva of patients with periodontal disease. Twenty-eight patients diagnosed with stage 3–4 periodontitis and 16 periodontally healthy subjects participated in this study. GCF was collected from sites with the deepest probing depth of each patient, and volume was measured using a Periotron 8000®. One mL of unstimulated saliva was also collected. Samples were analysed using a commercially available ELISA kit. The data were analysed using the Mann–Whitney U test, Pearson’s bivariate testing, and receiver operating characteristic curve. C5a was present in GCF from patients with periodontitis (1.06 ± 0.25 ng/mL) whilst it was undetected in controls. Saliva concentration was also significantly higher in periodontitis (1.82 ± 2.31 ng/mL) than controls (0.60 ± 0.72 ng/mL, p = 0.006). C5a levels were more pronounced in periodontitis in both oral fluids assessed by the present pilot study. These results suggest that the more pronounced levels of C5a in oral fluids from periodontitis patients indicate a potential role of this molecule in this disease pathogenesis, deserving to be better explored in subsequent studies.
Genotypic and Phenotypic Characteristics of Moraxella catarrhalis from Patients and Healthy Asymptomatic Participants among Preschool Children
Authors: Zhao Na , Ren Hongyu , Deng Jianping , Du Yinju , Li Qun , Zhou Pu , Zhou Haijian , Jiang Xiangkun , Qin Tian
Published: August 2022

(1) Background: M. catarrhalis can ascend into the middle ear, where it is a prevalent causative agent of otitis media in children, or enter the lower respiratory tract, where it is associated with community-acquired pneumonia (CAP). In this study, we aimed to provide an overview of the prevalence of M. catarrhalis in preschool children. (2) Methods: M. catarrhalis strains were isolated from samples. All isolates were characterized in terms of serotypes (STs), virulence genes, multilocus sequence type, and antibiotic susceptibility. (3) Results: The percentages of strains expressing lipooligosaccharides (LOSs), serotype A, B, C, or unknown were 67.61%, 15.71%, 4.28%, and 12.38%, respectively. Among the strains, 185 (88.10%) carried ompB2, 207 (98.57%) carried ompE, and 151 (71.90%) carried ompCD. The most frequently identified STs were ST449 (n = 13), ST64 (n = 11), and ST215 (n = 10). The resistance rates to the antibiotics cefuroxime, azithromycin, and erythromycin were 43.33%, 28.10%, and 39.05%, respectively. (4) Conclusions: High prevalence of some-specific ST types and high rates of antibiotic resistance indicate the necessity for an increased vigilance of resistant strains, a rational use of antibiotics in preschool children, and most importantly, the surveillance of healthy asymptomatic participants preschool children with M. catarrhalis. Our findings provide a platform for the development of novel M. catarrhalis vaccines.
Pulmonary Fibrosis and Hypereosinophilia in TLR9-/- Mice Infected by Cryptococcus gattii
Authors: da Silva-Junior Elias Barbosa , Diniz-Lima Israel , Silva Amanda Couto , Guimarães-de-Oliveira Joyce Cristina , Morrot Alexandre , Freire-de-Lima Leonardo , da Fonseca Leonardo Marques , de Brito-Gitirana Lycia , Decote-Ricardo Debora , de Matos Guedes Herbert Leonel , Freire-de-Lima Celio Geraldo
Published: August 2022

Cryptococcus gattii is a worldwide-distributed basidiomycetous yeast that can infect immunocompetent hosts. However, little is known about the mechanisms involved in the disease. The innate immune response is essential to the control of infections by microorganisms. Toll-like receptor 9 (TLR9) is an innate immune receptor, classically described as a non-methylated DNA recognizer and associated with bacteria, protozoa and opportunistic mycosis infection models. Previously, our group showed that TLR9-/- mice were more susceptible to C. gattii after 21 days of infection. However, some questions about the innate immunity involving TLR9 response against C. gattii remain unknown. In order to investigate the systemic cryptococcal infection, we evaluated C57BL/6 mice and C57BL/6 TLR9-/- after intratracheal infection with 104C. gattii yeasts for 21 days. Our data evidenced that TLR9-/- was more susceptible to C. gattii. TLR9-/- mice had hypereosinophilia in pulmonary mixed cellular infiltrate, severe bronchiolitis and vasculitis and type 2 alveolar cell hyperplasia. In addition, TLR9-/- mice developed severe pulmonary fibrosis and areas with strongly birefringent fibers. Together, our results corroborate the hypothesis that TLR9 is important to support the Th1/Th17 response against C. gattii infection in the murine experimental model.
Activity of a Pediatric Emergency Department of a Tertiary Center in Bologna, Italy, during SARS-CoV-2 Pandemic
Authors: Zama Daniele , Leardini Davide , Biscardi Lorenzo , Corsini Ilaria , Pierantoni Luca , Andreozzi Laura , Lanari Marcello
Published: August 2022

During the SARS-CoV-2 pandemic, the pediatric emergency department (ED) of Bologna, Emilia-Romagna, Italy faced a reorganization to better deal with the new clinical needs. We herein describe the main changes in the organization and in the attendances to our pediatric ED. From the 1 March 2020 to the 31 January 2022, 796 children positive for SARS-CoV-2 presented to our pediatric ED, but only 26 required hospitalizations, of which only 9 for COVID-19 related reasons. During this period, we also registered a temporal correlation between multisystem inflammatory syndrome in children (MIS-C) admissions and the peaks of SARS-CoV-2 infection in the Italian population. Respiratory syncytial virus (RSV) remained during last year the viral infection with the highest hospitalization rate. The analysis and description of the changes in the activity of the pediatric ED during the SARS-CoV-2 pandemic may help to better understand the routinary activity and be prepared for any possible new challenge.
Glucoraphanin Triggers Rapid Antidepressant Responses in a Rat Model of Beta Amyloid-Induced Depressive-like Behaviour
Authors: Tucci Paolo , Bove Maria , Sikora Vladyslav , Dimonte Stefania , Morgese Maria Grazia , Schiavone Stefania , Di Cesare Mannelli Lorenzo , Ghelardini Carla , Trabace Luigia
Published: August 2022

Glucoraphanin (GRA) is a natural compound that has shown beneficial effects in chronic diseases and in central nervous system disorders. Moreover, GRA displayed antidepressant activity in preclinical models. We have previously demonstrated that a single intracerebroventricular administration of soluble amyloid-beta 1-42 (sAβ 1-42) in rat evokes a depressive-like phenotype by increasing immobility frequency in the forced swimming test (FST). The aim of this work was to investigate the effect of GRA in naïve and in sAβ-1-42-treated rats by using the FST. Behavioural analyses were accompanied by neurochemical and biochemical measurements in the prefrontal cortex (PFC), such as serotonin (5-HT), noradrenaline (NA), kynurenine (KYN), tryptophan (TRP), reactive oxygen species (ROS) and the transcription nuclear factor kappa B (NF-kB) levels. We reported that GRA administration in naïve rats at the dose of 50 mg/kg reduced the immobility frequency in the FST and increased 5-HT and NA levels in the PFC compared to controls. At the same dose, GRA reverted depressive-like effects of sAβ 1-42 administration, restored the 5-HT levels and reduced NF-kB, KYN and ROS levels in PFC. In conclusion, GRA rapidly reverting depressive-like behaviour, together with biochemical and neurochemical alterations, might represent a safe and natural candidate for the treatment of depression.
Gypenoside XLIX Ameliorate High-Fat Diet-Induced Atherosclerosis via Regulating Intestinal Microbiota, Alleviating Inflammatory Response and Restraining Oxidative Stress in ApoE−/− Mice
Authors: Gao Ming , Heng Xing , Jin Jing , Chu Weihua
Published: August 2022

A high-fat choline diet (HFCD)-induced atherosclerosis model in ApoE−/− mice was established to explore the anti-atherosclerotic effects of gypenoside XLIX (GPE). It was found that HFCD-induced atherosclerotic index such as dyslipidemia, atherosclerotic plaque, inflammation, and gut microbiota dysfunction could be reduced by GPE treatment. GPE treatment could decrease Verrucomicrobia, Proteobacteria, and Actinobacteria abundance, and increase Firmicutes and Bacteroidetes population. Moreover, the Firmicutes/Bacteroidetes ratio increased significantly after treatment with GPE. After treatment with GPE, the relative abundance of trimethylamine-producing intestinal bacteria Clostridioides and Desulfovibrionaceae decreased while butyrate-producing bacteria such as Eubacterium, Roseburia, Bifidobacterium, Lactobacillus, and Prevotella increased significantly. The GPE group demonstrated higher SCFAs concentrations in the fecal sample, such as Acetic Acid, Propionic Acid, and Butyric Acid. Further pathway analysis showed that 29 metabolic pathways were appreciably disturbed during GPE treatment, including citrate cycle (TCA cycle); galactose and glycero-lipid-metabolism biosynthesis of unsaturated fatty acids, fatty acid biosynthesis. This study suggests that the anti-atherosclerotic effect of GPE is related to the substantial changes in intestinal microbiota and anti-inflammatory activity.
Zinc Oxide Nanoparticles as Potential Delivery Carrier: Green Synthesis by Aspergillus niger Endophytic Fungus, Characterization, and In Vitro/In Vivo Antibacterial Activity
Authors: Abdelkader Dalia H. , Negm Walaa A. , Elekhnawy Engy , Eliwa Duaa , Aldosari Basmah N. , Almurshedi Alanood S.
Published: August 2022

We aimed to synthesize zinc oxide nanoparticles (ZnO NPs) using the endophytic fungal extract of Aspergillus niger. The prepared ZnO NPs were characterized, and their in vitro and in vivo antibacterial activity was investigated. Isolated endophytic fungus identification was carried out using 18S rRNA. A. niger endophytic fungal extract was employed for the green synthesis of ZnO NPs. The in vitro antibacterial activity of the prepared ZnO NPs was elucidated against Staphylococcus aureus using the broth microdilution method and quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the in vivo antibacterial activity was elucidated using a systemic infection model in mice. The biosynthesized ZnO NPs showed a maximum optical density at 380 nm with characteristic peaks on the Fourier-transform infrared spectrum. The X-ray diffraction pattern was highly matched with a standard platform of zinc oxide crystals. Energy-dispersive X-ray analysis confirmed that the main composition of nanoparticles was zinc and oxygen atoms. Scanning and transmission electron microscopies showed spherical geometry with a smooth surface. Zeta potential measurements (26.6 ± 0.56 mV) verified the adequate stability of ZnO NPs. Minimum inhibitory concentrations of ZnO NPs against S. aureus isolates ranged from 8 to 128 µg/mL. Additionally, ZnO NPs revealed antibiofilm activity, resulting in the downregulation of the tested biofilm genes in 29.17% of S. aureus isolates. Regarding the in vivo experiment, ZnO NPs reduced congestion and fibrosis in liver and spleen tissues. They also improved liver function, increased the survival rate, and significantly decreased inflammatory markers (p < 0.05). ZnO NPs synthesized by A. niger endophytic fungus revealed a promising in vivo and in vitro antibacterial action against S. aureus isolates.
Self-Emulsifying Drug Delivery Systems (SEDDS): Measuring Energy Dynamics to Determine Thermodynamic and Kinetic Stability
Authors: Rehman Fiza Ur , Farid Arshad , Shah Shefaat Ullah , Dar Muhammad Junaid , Rehman Asim Ur , Ahmed Naveed , Rashid Sheikh Abdur , Shaukat Irfan , Shah Muddaser , Albadrani Ghadeer M. , Kamel Mohamed , Altyar Ahmed E. , Abdel-Daim Mohamed M. , Shah Kifayat Ullah
Published: August 2022

This research was designed to identify thermodynamically and kinetically stable lipidic self-emulsifying formulations through simple energy dynamics in addition to highlighting and clarifying common ambiguities in the literature in this regard. Proposing a model study, this research shows how most of the professed energetically stable systems are actually energetically unstable, subjected to indiscriminate and false characterization, leading to significant effects for their pharmaceutical applications. A self-emulsifying drug delivery system (SEDDS) was developed and then solidified (S-SEDDS) using a model drug finasteride. Physical nature of SEDDS was identified by measuring simple dynamics which showed that the developed dispersion was thermodynamically unstable. An in vivo study of albino rats showed a three-fold enhanced bioavailability of model drug with SEDDS as compared to the commercial tablets. The study concluded that measuring simple energy dynamics through inherent properties can distinguish between thermodynamically stable and unstable lipidic systems. It might lead to correct identification of a specific lipidic formulation and the application of appropriate characterization techniques accordingly. Future research strategies include improving their pharmaceutical applications and understanding the basic differences in their natures.
Real-World Use of Molnupiravir in the Treatment of Outpatients with SARS-CoV-2 Infection—A Patient Profile Based on the Experience of a Tertiary Infectious Disease Center
Authors: Streinu-Cercel Anca , Miron Victor Daniel , Oană Alina Alexandra , Irimia Mădălina , Popescu Ramona Ștefania , Dărămuș Ioana Andreea , Moțoi Maria Magdalena , Ceapraga Gabriela Jana , Săndulescu Oana
Published: August 2022

During the current pandemic, the gap between fundamental research and clinical practice has been narrowing at a faster pace than ever before. While clinical trials play the main role of confirming the safety and efficacy of new drugs, a drug’s introduction into clinical practice creates the need for further research in order to best position the use of the novel drug in terms of when, to whom, and how it would be best administered to achieve the best possible outcome under feasible clinical circumstances. We briefly present the results of a retrospective analysis of the characteristics of outpatients treated with molnupiravir in a tertiary care infectious disease hospital in Bucharest, Romania, between February and March 2022, when Romania was experiencing its fifth wave of COVID-19. A total of 46 outpatients received molnupiravir treatment and had complete clinical data available; of them, 56.5% (n = 20) were males and the median age was 48.5 years (IQR: 37.8, 67.0 years). A total of 54.2% (n = 26) of patients had at least one chronic condition. Of the 45 patients who underwent lung CT imaging evaluation, 13 (28.9%) showed changes suggestive of COVID-19 pneumonia. COVID-19 vaccination status was strongly protective for pneumonia (p = 0.002). All patients were symptomatic, and molnupiravir was initiated at a mean time from onset of symptoms of 3.5 (±1.5) days. At phone follow-up 5 days after the initial evaluation and initiation of molnupiravir treatment, all patients, except for one, confirmed a favorable course under treatment, with no worsening of COVID-19 severity and improvement in symptoms; none of them progressed to respiratory failure or required hospitalization. In conclusion, treatment was well tolerated and associated a favorable outcome of COVID-19 in routine practice in a clinical population that was slightly older and had a smaller burden of comorbidities and a higher rate of COVID-19 vaccination compared to that from the pivotal trial.
Carboxyl Group-Modified Myoglobin Induces TNF-α-Mediated Apoptosis in Leukemia Cells
Authors: Lee Yuan-Chin , Chiou Jing-Ting , Wang Liang-Jun , Shi Yi-Jun , Chen Ying-Jung , Chang Long-Sen
Published: August 2022

Previous studies have shown that chemical modification may increase the activity of proteins or confer novel activity to proteins. Some studies have indicated that myoglobin (Mb) is cytotoxic; however, the underlying mechanisms remain unclear. In this study, we investigated whether chemical modification of the carboxyl group by semicarbazide could promote the Mb cytotoxicity in human leukemia U937 cells and the underlying mechanism of semicarbazide-modified myoglobin (SEM-Mb)-induced U937 cell death. The semicarbazide-modified Mb (SEM-Mb) induced U937 cell apoptosis via the production of cleaved caspase-8 and t-Bid, while silencing of FADD abolished this effect. These findings suggest that SEM-Mb can induce U937 cell death by activating the death receptor-mediated pathway. The SEM-Mb inhibited miR-99a expression, leading to increased NOX4 mRNA and protein expression, which promoted SIRT3 degradation, and, in turn, induced ROS-mediated p38 MAPK phosphorylation. Activated p38 MAPK stimulated miR-29a-dependent tristetraprolin (TTP) mRNA decay. Downregulation of TTP slowed TNF-α mRNA turnover, thereby increasing TNF-α protein expression. The SEM-Mb-induced decrease in cell viability and TNF-α upregulation were alleviated by abrogating the NOX4/SIRT3/ROS/p38 MAPK axis or ectopic expression of TTP. Taken together, our results demonstrated that the NOX4/SIRT3/p38 MAPK/TTP axis induces TNF-α-mediated apoptosis in U937 cells following SEM-Mb treatment. A pathway regulating p38 MAPK-mediated TNF-α expression also explains the cytotoxicity of SEM-Mb in the human leukemia cell lines HL-60, THP-1, K562, Jurkat, and ABT-199-resistant U937. Furthermore, these findings suggest that the carboxyl group-modified Mb is a potential structural template for the generation of tumoricidal proteins.
Antioxidant, Antibacterial, Enzyme Inhibitory, and Anticancer Activities and Chemical Composition of Alpinia galanga Flower Essential Oil
Authors: Tian Yufeng , Jia Xiaoyan , Wang Qinqin , Lu Tingya , Deng Guodong , Tian Minyi , Zhou Ying
Published: August 2022

Alpinia galanga is widely cultivated for its essential oil (EO), which has been used in cosmetics and perfumes. Previous studies of A. galanga focussed mostly on the rhizome but seldom on the flower. Therefore, this study was designed to identify the chemical composition of A. galanga flower EO and firstly estimate its antioxidant, antibacterial, enzyme inhibitory, and anticancer activities. According to the results of the gas chromatography with flame ionization or mass selective detection (GC-FID/MS) analysis, the most abundant component of the EO was farnesene (64.3%), followed by farnesyl acetate (3.6%), aceteugenol (3.2%), eugenol (3.1%), E-nerolidol (2.9%), decyl acetate (2.4%), octyl acetate (2.0%), sesquirosefuran (1.9%), (E)-β-farnesene (1.7%), and germacrene D (1.5%). For the bioactivities, the EO exhibited moderate DPPH and ABTS radical scavenging effects with IC50 values of 138.62 ± 3.07 μg/mL and 40.48 ± 0.49 μg/mL, respectively. Moreover, the EO showed strong-to-moderate antibacterial activities with various diameter of inhibition zone (DIZ) (8.79–14.32 mm), minimal inhibitory concentration (MIC) (3.13–6.25 mg/mL), and minimal bactericidal concentration (MBC) (6.25–12.50 mg/mL) values against Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli, and Proteus vulgaris. Interestingly, the EO possessed remarkable α-glucosidase inhibition (IC50 = 0.16 ± 0.03 mg/mL), which was equivalent to that of the positive control acarbose (IC50 = 0.15 ± 0.01 mg/mL) (p > 0.05). It showed moderate tyrosinase inhibition (IC50 = 0.62 ± 0.09 mg/mL) and weak inhibitory activity on acetylcholinesterase (AChE) (IC50 = 2.49 ± 0.24 mg/mL) and butyrylcholinesterase (BChE) (IC50 = 10.14 ± 0.59 mg/mL). Furthermore, the EO exhibited considerable selective cytotoxicity to K562 cells (IC50 = 41.55 ± 2.28 μg/mL) and lower cytotoxicity to non-cancerous L929 cells (IC50 = 120.54 ± 8.37 μg/mL), and it induced K562 cell apoptosis in a dose-dependent manner. Hence, A. galanga flower EO could be regarded as a bioactive natural product with great application potential in the pharmaceutical field.
Farnesiferol C Exerts Antiproliferative Effects on Hepatocellular Carcinoma HepG2 Cells by Instigating ROS-Dependent Apoptotic Pathway
Authors: Alafnan Ahmed , Alamri Abdulwahab , Alanazi Jowaher , Hussain Talib
Published: August 2022

Farnesiferol C (Far-C) is a coumarin commonly extracted from Ferula asafetida and is popularly used as a traditional source of natural remedy. Liver cancer or hepatocellular carcinoma (HCC) has emerged as a major cause behind cancer burden, and limited therapeutic interventions have further aggravated the clinical management of HCC. In the present study, the authors tested the hypothesis that Far-C-instigated oxidative stress resulted in anti-proliferation and apoptosis instigation within human liver cancer HepG2 cells. The observations reported herewith indicated that Far-C exerted considerable cytotoxic effects on HepG2 cells by reducing the cell viability (p < 0.001) in a dose-dependent manner. Far-C exposure also resulted in enhanced ROS production (p < 0.01) which subsequently led to loss of mitochondrial membrane potential. Far-C-instigated oxidative stress also led to enhanced nuclear fragmentation and condensation as revealed through Hoechst-33342. These molecular changes post-Far-C exposure also incited apoptotic cell death which concomitantly led to significant activation of caspase-3 (p < 0.001). Furthermore, Far-C exhibited its competence in altering the expression of genes involved in apoptosis regulation (Bax, Bad, and Bcl2) along with genes exerting regulatory effects on cell cycle (cyclinD1) and its progression (p21Cip1 and CDK4). The evidence thus clearly shows the preclinical efficacy of Far-C against HepG2 cells. However, further mechanistic investigations deciphering the alteration of different pathways post-Far-C exposure will be highly beneficial.
Concept of Hybrid Drugs and Recent Advancements in Anticancer Hybrids
Authors: Singh Ankit Kumar , Kumar Adarsh , Singh Harshwardhan , Sonawane Pankaj , Paliwal Harshali , Thareja Suresh , Pathak Prateek , Grishina Maria , Jaremko Mariusz , Emwas Abdul-Hamid , Yadav Jagat Pal , Verma Amita , Khalilullah Habibullah , Kumar Pradeep
Published: August 2022

Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011–2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.
Alzheimer’s Disease Severity Is Associated with an Imbalance in Serum Levels of Enzymes Regulating Plasmin Synthesis
Authors: Angelucci Francesco , Veverova Katerina , Katonová Alžbeta , Piendel Lydia , Vyhnalek Martin , Hort Jakub
Published: August 2022

Alzheimer’s disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions, and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of beta amyloid (Aβ) and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated the levels of tPA and PAI-1 in serum from 40 AD and 40 amnestic mild cognitively impaired (aMCI) patients compared to 10 cognitively healthy controls. Moreover, we also examined the PAI-1/tPA ratio in these patient groups. Venous blood was collected and the PAI-1 and tPA serum concentrations were quantified using sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive performance measured using the Mini-Mental Status Exam (MMSE). Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting cognitive decline in AD.
Assembly of Celastrol to Zeolitic Imidazolate Framework-8 by Coordination as a Novel Drug Delivery Strategy for Cancer Therapy
Authors: Wang Na , Li Yifan , He Fei , Liu Susu , Liu Yuan , Peng Jinting , Liu Jiahui , Yu Changyuan , Wang Shihui
Published: August 2022

Celastrol (Cel), a compound derived from traditional Chinese medicine Tripterygium wilfordii Hook. F, has attracted considerable attention as an anticancer drug. However, its clinical application is limited due to its low bioavailability and potential toxicity. With the advancement of nanoscale metal organic frameworks (MOF), the nano-delivery of drugs can effectively improve those disadvantages. Nevertheless, hydrophobic drugs apparently cannot be encapsulated by the hydrophilic channels of MOF-based drug delivery systems. To address these issues, a new assembly strategy for hydrophobic Cel was developed by coordinating the deprotonated Cel to zeolitic imidazolate framework-8 (ZIF-8) with the assistance of triethylamine (Cel-ZIF-8). This strategy greatly elevates the assembly efficiency of Cel from less than 1% to ca. 80%. The resulted Cel-ZIF-8 remains stable in the physiological condition while dissociating and releasing Cel after a 45-minute incubation in an acidic tumor microenvironment (pH 5.5). Furthermore, Cel-ZIF-8 is proved to be easily taken up by cancer cells and exhibits a better therapeutic effect on tumor cells than free Cel. Overall, the Cel-ZIF-8 provides a novel assembly strategy for hydrophobic drugs, and the findings are envisaged to facilitate the application of Cel in cancer therapies.
Factors and Practices Associated with Self-Medicating Children among Mexican Parents
Authors: Alonso-Castro Angel Josabad , Ruiz-Noa Yeniley , Martínez-de la Cruz Gissela Cristel , Ramírez-Morales Marco Antonio , Deveze-Álvarez Martha Alicia , Escutia-Gutiérrez Raymundo , Carranza-Álvarez Candy , Domínguez Fabiola , Maldonado-Miranda Juan José , Ruiz-Padilla Alan Joel
Published: August 2022

Background: Pediatric self-medication is based on the subjective interpretation of symptoms in children by the mother or an adult, the decision to self-medicate is made by a third party. The objective of this work is to provide information on the factors and practices associated with the self-medication of children among parents in Mexico. Methods: A cross-sectional and descriptive study was conducted between June 2020 and December 2021 on Mexican parents with children under 12 years of age. Online questionnaires were completed with sections on sociodemographic characteristics, use of medicines or medicinal plants and their treated symptoms, sources of collection, and their recommendation. Results: A total of 9905 online surveys were completed with representation from the 32 states of Mexico, and the prevalence of self-medication was 49.6% (n = 4908). Associated factors were age, having two or more children, children with chronic illnesses, medium educational level, unemployment or employment unrelated to health, medium and high socioeconomic level, and lack of medical security. Respondents self-medicated their children on the recommendation of a family member or friend (55.8%), and own initiative (28%). The most used medication was VapoRub (61.3%), followed by paracetamol (56.9%) and chamomile (33.1%), and the most prevalent symptoms were flu/flow (47.7%) followed by cough (34.2%). The main reasons were perceiving symptoms as not serious (69.9%) and reusing medications (51.9%). Conclusions: There is a high prevalence of self-medication in children in Mexico, mainly associated with children with chronic diseases and families with three or more children.
Anti-Inflammatory Therapy for Temporomandibular Joint Osteoarthritis Using mRNA Medicine Encoding Interleukin-1 Receptor Antagonist
Authors: Deng Jia , Fukushima Yuta , Nozaki Kosuke , Nakanishi Hideyuki , Yada Erica , Terai Yuki , Fueki Kenji , Itaka Keiji
Published: August 2022

Messenger RNA (mRNA) is an emerging drug modality for protein replacement therapy. As mRNA efficiently provides protein expression in post-mitotic cells without the risk of insertional mutagenesis, direct delivery of mRNA can be applied, not only as an alternative to gene therapy, but also for various common diseases such as osteoarthritis (OA). In this study, using an mRNA-encoding interleukin-1 receptor antagonist (IL-1Ra), we attempted anti-inflammatory therapy in a rat model of the temporomandibular joint (TMJ) OA, which causes long-lasting joint pain with chronic inflammation. For the intra-articular injection of mRNA, a polyplex nanomicelle, our original polymer-based carrier, was used to offer the advantage of excellent tissue penetration with few immunogenic responses. While the protein expression was transient, a single administration of IL-1Ra mRNA provided sustained pain relief and an inhibitory effect on OA progression for 4 weeks. The mRNA-loaded nanomicelles provided the encoded protein diffusely in the disc and articular cartilage without upregulation of the expression levels of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α (TNF-α). This proof-of-concept study demonstrates how anti-inflammatory proteins delivered by mRNA delivery using a polyplex nanomicelle could act to alleviate OA, stimulating the development of mRNA therapeutics.
Editorial on the “Special Issue in Honor of Dr. Michael Weber’s 70th Birthday: Photodynamic Therapy: Rising Star in Pharmaceutical Applications”
Authors: Preis Eduard , Wojcik Matthias , Litscher Gerhard , Bakowsky Udo
Published: August 2022

Thousands of years ago, phototherapy or heliotherapy was performed by ancient Egyptians, Greeks, and Romans [...]
Novel αO-conotoxin GeXIVA[1,2] Nonaddictive Analgesic with Pharmacokinetic Modelling-Based Mechanistic Assessment
Authors: Zhu Xiaoyu , Yuan Mei , Wang Huanbai , Zhangsun Dongting , Yu Gang , Che Jinjing , Luo Sulan
Published: August 2022

αO-conotoxin GeXIVA[1,2] was isolated in our laboratory from Conus generalis, a snail native to the South China Sea, and is a novel, nonaddictive, intramuscularly administered analgesic targeting the α9α10 nicotinic acetylcholine receptor (nAChR) with an IC50 of 4.61 nM. However, its pharmacokinetics and related mechanisms underlying the analgesic effect remain unknown. Herein, pharmacokinetics and multiscale pharmacokinetic modelling in animals were subjected systematically to mechanistic assessment for αO-conotoxin GeXIVA[1,2]. The intramuscular bioavailability in rats and dogs was 11.47% and 13.37%, respectively. The plasma exposure of GeXIVA[1,2] increased proportionally with the experimental dose. The plasma protein binding of GeXIVA[1,2] differed between the tested animal species. The one-compartment model with the first-order absorption population pharmacokinetics model predicted doses for humans with bodyweight as the covariant. The pharmacokinetics-pharmacodynamics relationships were characterized using an inhibitory loss indirect response model with an effect compartment. Model simulations have provided potential mechanistic insights into the analgesic effects of GeXIVA[1,2] by inhibiting certain endogenous substances, which may be a key biomarker. This report is the first concerning the pharmacokinetics of GeXIVA[1,2] and its potential analgesic mechanisms based on a top-down modelling approach.
RETRACTED: Amitriptyline-Based Biodegradable PEG-PLGA Self-Assembled Nanoparticles Accelerate Cutaneous Wound Healing in Diabetic Rats
Authors: Asfour Hani , Alhakamy Nabil , Ahmed Osama , Fahmy Usama , El-moselhy Mohamed , Rizg Waleed , Alghaith Adel , Eid Basma , Abdel-Naim Ashraf
Published: August 2022

The aim of this work was to study the healing activity of amitriptyline (Amitrip) in rat diabetic wounds. A nanoformula of the drug was prepared as Amitrip-based biodegradable PEG-PLGA self-assembled nanoparticles (Amitrip-NPs) with a mean particle size of 67.4 nm. An in vivo investigation was conducted to evaluate the wound-healing process of Amitrip-NPs in streptozotocin-induced diabetic rats. Wound contraction was accelerated in rats treated with Amitrip-NPs. Histological examinations confirmed these findings, with expedited remodeling and collagen deposition in the NPs-treated animals. The formula showed anti-inflammatory activities as demonstrated by inhibition of interleukin-6 (IL-6) expression and tumor necrosis factor-α (TNF-α) expression, as well as enhanced expression of interleukin-10 (IL-10). In addition, Amitrip-NPs protected against malondialdehyde (MDA) buildup and superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymatic exhaustion. The pro-collagen activity of Amitrip-NPs was confirmed by the observed enhancement of hydroxyproline wounded skin content, upregulation of Col 1A1 mRNA expression and immune expression of collagen type IV expression. Further, Amitrip-NPs significantly increased expression transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-B (PDGF-B) and cluster of differentiation 31 (CD31). In conclusion, the developed Amitrip-NPs expedited wound healing in diabetic rats. This involves anti-inflammatory, antioxidant, pro-collagen and angiogenic activities of the prepared NPs. This opens the gate for evaluating the usefulness of other structurally related tricyclic antidepressants in diabetic wounds.