bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minocycline Promotes Functional Recovery in Ischemic Stroke by Modulating Microglia Polarization Through STAT1/STAT6 Pathways
Authors: Lu Yunnan , Zhou Mingming , Li Yun , Li Yan , Hua Ye , Fan Yi 
Published: January 2021

Abstract

BackgroundIncreasing evidence suggests that microglia experience two distinct phenotypes after acute ischemic stroke (AIS): a deleterious M1 phenotype and a neuroprotective M2 phenotype. Promoting the phenotype shift of M1 microglia to M2 microglia is thought to improve functional recovery after AIS. Minocycline, a tetracycline antibiotic, can improve functional recovery after cerebral ischemia in pre-clinical and clinical research. However, the role and mechanisms of minocycline in microglia polarization is unclear.MethodsUsing the transient middle cerebral artery occlusion - reperfusion (MCAO/R) model, we treated mice with saline or different minocycline concentration (10, 25, or 50 mg/kg, i.p., daily for 2 wk) at 24 h after reperfusion. Neurobehavioral evaluation, rotarod test, and corner turning test were carried out on day 14 after reperfusion. Then, neuronal injury, reactive gliosis, and microglia polarization were performed on day 7 following MCAO/R. Finally, we treated primary microglial cultures with LPS (Lipopolysaccharide; 100 ng/mL) plus IFN-γ (20 ng/mL) 24 h to induce M1 phenotype and observed the effects of minocycline on the M1/M2-related mRNAs and the STAT1/STAT6 pathway.ResultsWe found that a 14-day treatment with minocycline increased the survival rate and promoted functional outcomes evaluated with neurobehavioral evaluation, rotarod test, and corner turning test. Meanwhile, minocycline reduced the brain infarct volume, alleviated neuronal injury, and suppressed reactive gliosis on day 7 following MCAO/R. Moreover, we observed an additive effect of minocycline on microglia polarization to the M1 and M2 phenotypes in vivo and in vitro. In the primary microglia, we further found that minocycline prevented neurons from OGD/R-induced cell death in neuron-microglia co-cultures via regulating M1/M2 microglia polarization through the STAT1/STAT6 pathway. ConclusionMinocycline promoted microglial M2 polarization and inhibited M1 polarization, leading to neuronal survival and neurological functional recovery. The findings deepen our understanding of the mechanisms underlying minocycline-mediated neuroprotection in AIS.
Modulatory Effects of Caffeine and Pentoxifylline on Aromatic Antibiotics: A Role for Heterocomplex Formation
Authors: Woziwodzka Anna , Krychowiak-Maśnicka Marta , Gołuński Grzegorz , Felberg Anna , Borowik Agnieszka , Wyrzykowski Dariusz , Piosik Jacek 
Published: January 2021

Abstract
Antimicrobial resistance is a major healthcare threat globally. Xanthines, including caffeine and pentoxifylline, are attractive candidates for drug repurposing, given their well-established safety and pharmacological profiles. This study aimed to analyze potential interactions between xanthines and aromatic antibiotics (i.e., tetracycline and ciprofloxacin), and their impact on antibacterial activity. UV-vis spectroscopy, statistical-thermodynamical modeling, and isothermal titration calorimetry were used to quantitatively evaluate xanthine-antibiotic interactions. The antibacterial profiles of xanthines and xanthine-antibiotic mixtures towards important human pathogens Staphylococcus aureus, Enterococcus faecium, Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, and Enterobacter cloacae were examined. Caffeine and pentoxifylline directly interact with ciprofloxacin and tetracycline, with neighborhood association constant values of 15.8–45.6 M− 1 and enthalpy change values up to -4 kJ M− 1. Caffeine showed antibacterial activity (minimum inhibitory concentration, 4–8 mg/mL) toward Gram-negative bacteria. Caffeine enhanced the antibacterial activity of the tested antibiotics in most pathogens tested. Antagonistic effects of caffeine were observed only with ciprofloxacin toward Gram-positive pathogens. Xanthines interact with aromatic antibiotics at the molecular and in vitro antibacterial activity level. Given considerable exposure to caffeine and pentoxifylline, these interactions are relevant for the effectiveness of antibacterial pharmacotherapy, and may help to identify optimal treatment regimens in the era of multidrug resistance.
Performance enhancement of in-network probabilistic aggregation (PEPA) for vehicular ad-hoc networks
Authors: Kumar Rajeev , Kumar Dilip , Kumar Dinesh 
Published: January 2021

Abstract
In the current scenario of vehicular communication, it is very difficult to believe that the aggregated packet of information is not malicious. The algorithm is developed to allocate probability to the packet transmitted by the cluster head depending upon, the number of vehicles involved in creating a clustered information. The aggregated packet with the highest value of probabilistic correctness is considered by the receiving-end cluster head when multiple packets of similar information with related timestamps are received. The performance of the technique is tested under varying vehicular densities and data-sending rates. This scheme provides robust aggregation performance in comparison to the existing state-of-the-art structured and structure-free aggregation techniques.
INCÓGNITAS ESTRATÉGICAS
Authors: McGoey Linsey 
Published: January 2021

Ao desenvolver uma agenda para o estudo social da ignorância, este artigo apresenta a sociologia das incógnitas estratégicas: a investigação das formas multifacetadas pelas quais a ignorância pode ser aproveitada como um recurso, permitindo que o conhecimento seja defletido, obscurecido, escondido ou ampliado de uma maneira que amplia a extensão do que permanece ininteligível. Em contraste com as preocupações teóricas que fundamentam o estudo da acumulação de conhecimento, o foco na importância de incógnitas estratégicas resiste à tendência de valorizar o conhecimento ao invés da ignorância, ou pressupor que a aquisição de mais conhecimento está relacionado de forma automática ou linear à obtenção de mais poder social ou político. Ao refinar e desafiar a suposição de que as sociedades liberais modernas inevitavelmente prosperam no acúmulo de informações sobre as personas públicas, psiques privadas, hábitos de consumo ou tendências políticas dos cidadãos, os artigos nesta edição especial exploram como o cultivo de incógnitas estratégicas continuam a ser um recurso - talvez o maior recurso - para aqueles em uma posição de poder e para aqueles sujeitos a ele.
Palavras-chave: sociologia da ignorância; incógnitas estratégicas; ambiguidade; risco; incerteza.
Malaria-induced Alterations of Drug Kinetics and Metabolism in Rodents and Humans
Authors: De-Oliveira Ana C.A.X. , Paumgartten Francisco J.R. 
Published: January 2021

Background::
Infections and inflammation lead to a downregulation of drug metabolism and kinetics
in experimental animals. These changes in the expression and activities of drug-metabolizing enzymes may affect
the effectiveness and safety of pharmacotherapy of infections and inflammatory conditions.

Objective::
In this review, we addressed the available evidence on the effects of malaria on drug metabolism activity
and kinetics in rodents and humans.

Results::
An extensive literature review indicated that infection by Plasmodium spp consistently decreased the
activity of hepatic Cytochrome P450s and phase-2 enzymes as well as the clearance of a variety of drugs in
mice (lethal and non-lethal) and rat models of malaria. Malaria-induced CYP2A5 activity in the mouse liver
was an exception. Except for paracetamol, pharmacokinetic trials in patients during acute malaria and in convalescence
corroborated rodent findings. Trials showed that, in acute malaria, clearance of quinine, primaquine,
caffeine, metoprolol, omeprazole, and antipyrine is slower and that AUCs are greater than in convalescent individuals.

Conclusion::
Notwithstanding the differences between rodent models and human malaria, studies in P. falciparum
and P. vivax patients confirmed rodent data showing that CYP-mediated clearance of antimalarials and
other drugs is depressed during the symptomatic disease when rises in levels of acute-phase proteins and inflammatory
cytokines occur. Evidence suggests that inflammatory cytokines and the interplay between malaria-activated
NF-kB-signaling and cell pathways controlling phase 1/2 enzyme genes transcription mediate drug
metabolism changes. The malaria-induced decrease in drug clearance may exacerbate drug-drug interactions,
and the occurrence of adverse drug events, particularly when patients are treated with narrow-margin-of-safety
medicines.
In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring
Authors: Ferreira Abigail , Martins Helena , Oliveira José C. , Lapa Rui , Vale Nuno 
Published: January 2021

Background::
Vancomycin has been in clinical use for nearly 50 years and remains the first-line treatment
option for Gram-positive infections, including methicillin-resistant Staphylococcus aureus (MRSA).
There are multiple strategies to monitor therapy and adjust the dose of this antibiotic. AUC24/MIC ratio has
been demonstrated to be the best parameter to predict the effectiveness and safety of vancomycin, and a target
ratio of ≥400 is recommended. Still, trough and peak serum levels at steady-state conditions have been used in
clinical settings as an accurate and practical method to monitor vancomycin.

Methods::
In this work, we collected and analyzed clinical information of patients being treated in a hospital
center in Porto (Portugal) and studied the pharmacokinetics of vancomycin in silico, developing several physiologically
based pharmacokinetic (PBPK) models using simulation software GastroPlus™. Different dosages
and treatment regimens were studied, and the influence of patients’ age, weight and renal function was evaluated;
a simulation population was also performed.

Results::
A linear effect of dose and a significant influence of weight and renal function in plasmatic levels of
vancomycin was observed.

Conclusion::
The results of this work corroborate the accumulation of vancomycin in plasma and identify some
parameters that influence the pharmacokinetics of this antibiotic. The importance of therapeutic monitoring of
vancomycin is highlighted, and the usefulness of in silico tools, namely PBPK modeling, is demonstrated.
Rapid Profiling and Identification of Vitexin Metabolites in Rat Urine, Plasma and Faeces after Oral Administration Using a UHPLC-Q-Exactive Orbitrap Mass Spectrometer Coupled with Multiple Data-mining Methods
Authors: Dong Pingping , Shi Lei , Wang Shaoping , Jiang Shan , Li Haoran , Dong Fan , Xu Jing , Dai Long , Zhang Jiayu 
Published: January 2021

Background::
Vitexin is a natural flavonoid compound with multiple pharmacological activities and
is extracted from the leaves and seeds of Vitex negundo L. var. cannabifolia (Sieb. et Zucc.) Hand.-Mazz. However,
the metabolite characterization of this component remains insufficient.

Objective::
To establish a rapid profiling and identification method for vitexin metabolites in rat urine, plasma
and faeces after oral administration using a UHPLC-Q-Exactive orbitrap mass spectrometer were coupled with
multiple data-mining methods.

Methods::
In this study a simple and rapid systematic strategy for the detection and identification of constituents
was proposed based on UHPLC-Q-Exactive Orbitrap mass spectrometry in parallel reaction monitoring mode
combining diagnostic fragment ion filtering techniques.

Results::
A total of 49 metabolites were fully or partially characterized based on their accurate mass, characteristic
fragment ions, retention times, corresponding ClogP values, and so on. It is obvious that C-glycosyl
flavonoids often display an [M+H-120]+ ion that represents the loss of C4H8O4. As a result, these metabolites
were presumed to be generated through glucuronidation, sulfation, deglucosylation, dehydrogenation, methylation,
hydrogenation, hydroxylation, ring cleavage and their composite reactions. Moreover, the characteristic
fragmentation pathways of flavonoids, chalcones and dihydrochalcones were summarized for the subsequent
metabolite identification.

Conclusion::
The current study provided an overall metabolic profile of vitexin which will be of great help in
predicting the in vivo pharmacokinetic profiles and understanding the action mechanism of this active ingredient.
Different Inductive Effects of Praziquantel Racemate and its Enantiomers on the Enzyme CYP3A4 Mediated by Pregnane X Receptor and its Variants
Authors: Meng Ran , Zhang Xueli , Wang Haina , Zhang Danlu , Zhao Xin 
Published: January 2021

Background::
Praziquantel (PZQ), which possesses an asymmetric center, is classified as a pyrazinoisoquinoline
and has been the mainstay in the treatment of schistosomiasis since 1980. PZQ undergoes a pronounced
first-pass metabolism in the liver through the CYP450 system which could be mediated by nuclear receptors.

Objective::
The purpose of this study was to investigate the possible different induction effects of CYP3A4 by
PZQ racemate and enantiomers via the pregnane X receptor (PXR) and the effect of PXR polymorphism on the
induction potency of PZQs.

Methods::
The dual-luciferase reporter gene systems constructed in HepG2 cells were used to measure the abilities
of PZQs to induce CYP3A4 expression mediated by PXR. The mRNA and protein levels of CYP3A4 were
evaluated by polymerase chain reaction (PCR) and western blotting, respectively.

Results::
In HepG2 cells transfected with PXRwt, PXR158, PXR163, PXR370 or PXR403 expression plasmids,
PZQ racemate and its enantiomers up-regulated the luciferase activity in a concentration-dependent manner,
while reaching saturation after transfected with PXR379 expression plasmids. The mRNA and protein expression
of CYP3A4 was effectively activated in PXR-transfected HepG2 cells. The induction ability of CYP3A4
mediated by PXR activation by PZQ racemate and its enantiomers were statistically different between the same
PXR group and different PXR groups.

Conclusion::
The enantioselective induction effects of PZQs on CYP3A4 were related to the enantioselective activations
of PXR by PZQs and were influenced by the PXR gene polymorphism. These findings provide a basis
for further understanding the enantiomeric metabolism and the variable efficacy of PZQs.
Serum Interleukin-33 is a Predictor of Depression in Patients with Acute Ischemic Stroke
Authors: Chen Zhenlei , Zhang Rongrong , Wu Yanping , Fu Qing , Qin Xinyue 
Published: January 2021

Objective::
The study aimed to investigate the relationship between serum interleukin-33
(IL-33) concentrations and poststroke depression (PSD) in patients with acute ischemic stroke
(AIS).

Methods::
Serum IL-33 concentrations were determined using an enzyme-linked immunosorbent assay.
Patients were assigned to the PSD group after a six-month follow-up if their score on the 17-
item Hamilton Rating Scale for Depression was ≥7 or to the non-PSD group if their score was <7.
IL-33 was used to predict the risk of PSD using multivariate logistic regression analysis, while a receiver
operating characteristic (ROC) curve was used to analyze the accuracy of PSD prediction. In
addition, the modified Rankin scale (mRS) was used for follow-up scoring six months after disease
onset.

Results::
A total of 151 AIS patients and 40 healthy controls were included in this study. ROC
curve results showed that the area under the curve was 0.684 (95% confidence interval:
0.594-0.774,Ρ=0.001) for IL-33 as a predictor of PSD. When the IL-33 concentration was ≤71.85
ng/L, prediction sensitivity and specificity were 77.5% and 57.3%, respectively. Multivariate logistic
regression analysis showed that IL-33 concentration of ≤71.85 ng/L was an independent predictor
of PSD (95% CI: 1.129-7.515, P=0.027). The follow-up mRS data showed that serum IL-33 is
a protective prognosis factor in patients with AIS (95% CI: 0.954-0.997, P=0.024).

Conclusions::
Serum IL-33 is an independent predictor of PSD and a protective prognosis factor in
patients with AIS.
Assessing the Effectiveness of a Telemedicine Initiative in Clinical Management of Children Living with HIV/AIDS in Maharashtra, India
Authors: Manglani Mamta , Gabhale Yashwant , Lala Mamatha Murad , Balakrishnan Sudha , Bhuyan Khanindra , Rewari Bharat Bhushan , Setia Maninder Singh 
Published: January 2021

Aims:To evaluate the effectiveness of telemedicine in the clinical management of children living with HIV/AIDS in resource-limited settingsBackground:Telemedicine is an important mechanism for service delivery in health care settings, both in resource-rich and resource-poor settings. Such service delivery mechanisms have shown to be associated with virologic suppression and higher CD4 counts. These services are also associated with improved access, shorter visiting times, and higher patient satisfaction.Objective:We designed the present two-group comparison study to compare the clinical evaluation and management of children in the anti-retroviral therapy (ART) centres linked to telemedicine facility with those who are not linked to this facility in Maharashtra, India.Methods:We analysed clinical records from six ART centres in Maharashtra; of these, 250 children were in the linked ART centres and 301 were in the non-linked ART centres. The outcomes were classified according to investigations, management, and monitoring. For management, we evaluated: 1) Initiation of cotrimoxazole prophylaxis; 2) Children not initiated on ART when required; 3) ART regime after appropriate investigations; and 4) Change of regime (if immunologically indicated). For monitoring, we assessed the haematological monitoring of children on ART.Result:The mean (SD) ages of children in linked and non-linked ART centres were 10.8 (4.6) and 10.9 (4.6) years, respectively (p=0.80). After adjusting for individual and structural level variables, physical examination (OR: 2.0, 95% CI; 1.2, 3.2), screening for tuberculosis (OR: 12.9, 95% CI: 2.0, 82.9) and cotrimoxazole prophylaxis were significantly more likely in the linked centres compared with non-linked centres (OR: 1.8, 95% CI: 1.4, 2.2). A higher proportion of children eligible for ART were not initiated on treatment in the non-linked centres compared with linked centres (26% vs. 8%, p=0.06). Children were less likely to be initiated on zidovudine-based regimens without baseline haemoglobin or with baseline haemoglobin of less than 9 gm% in linked centres (OR: 0.7, 95% CI: 0.6, 0.8). Similarly, children in the linked centres were less likely to have been started on nevirapine-based regimens without baseline liver enzymes (OR: 0.8, 95% CI: 0.7, 0.9).Conclusions:Thus, the overall clinical management of Children Living with HIV/ AIDS (CLHA) was better in ART centres linked with the telemedicine initiative compared with those who were not linked. Children in the linked ART centres were more likely to have a complete baseline assessment (physical, hematological, radiological, and screening for TB); the presence of a pediatrician in the centres was helpful.
Diagnosis of Inflammatory Bowel Disease by Abdominal Ultrasound and Color Doppler Techniques
Authors: Ahmed Rehab , Debian Hossam , Fawzi Mohamed , Elsergany Heba Fadl , Soliman Moataz Yousry , Mohmed Ahmed Abdel Haleem , Kandil Alaa , Elmaghraby Mostafa Bedair , Abd-Elsalam Sherief , Abo-Amer Yousry Esam-Eldin 
Published: January 2021

Background & Aims:
The utility of ultrasound and color Doppler in the diagnosis and
evaluation of inflammatory bowel diseases (IBD) has not been studied enough. Therefore, the aim
of the current study was to evaluate the importance of conventional abdominal ultrasound and color
Doppler in diagnosing IBD and assessing disease activity.

Methods:
The study was conducted at the National Hepatology and Tropical Medicine Research Institute
(NHTMRI) between July 2018 and January 2019, in which 150 patients were suffering from
diarrhea, dysentery, tenesmus, or rectal bleeding were evaluated by colonoscopy, high-resolution
ultrasound, and color Doppler scans.

Results:
The present study was conducted on 150 patients; 84 (56%) had ulcerative colitis (UC),
16 (10.7%) had Crohn's disease (CD), and 50 (33.3%) had normal colonoscopy results with a mean
age 37.2 ± 9.059. The superior mesenteric Artery Peak Systolic Velocity (SMA-PSV) and End Diastolic
Velocity (EDV) were significantly higher in both UC and CD than in the control group;
however, pulsatility index (PI) was significantly higher in the control group than both UC and CD.
However, there was no significant difference between UC and CD. The inferior mesenteric artery
PSV and EDV were significantly higher in both UC and CD than in the control group.

Conclusions:
Doppler ultrasound findings of SMA and IMA correlate with the incidence of inflammatory
bowel disease, the site of disease, and its activity.
90Y-DOTA-Nimotuzumab: Synthesis of a Promising β− Radiopharmaceutical
Authors: Scotognella Teresa , Maccora Daria , Bruno Isabella , Chinol Marco , Castagnola Massimo , Collamati Francesco , Mancini-Terraciano Carlo , Morganti Silvio , Bocci Valerio , Camillocci Elena Solfaroli , Rotili Dante , Cartoni Antonella , Fratoddi Ilaria , Marini Federica , Venditti Iole , Faccini Riccardo , Giordano Alessandro 
Published: January 2021

Background::
Nimotuzumab is a humanized anti-epidermal growth factor receptor (EGFR) monoclonal
antibody, nowadays used for tumour immunochemotherapy. This study aimed to label the conjugate DOTA-nimotuzumab
with yttrium-90, in order to provide a β- emitting radioimmunoconjugate (90Y-DOTA-nimotuzumab) potentially useful to
assess the feasibility of a new radio-guided surgery approach.

Methods::
The synthesis of 90Y-DOTA-nimotuzumab was performed in two days. Nimotuzumab was conjugated with a 50
fold excess of DOTA and then labelled with 90Y3+. The 90Y-DOTA-nimotuzumab preparation was optimized considering
several parameters such as pH, temperature and reaction volume. Moreover, the 90Y-DOTA-nimotuzumab stability was
evaluated in human plasma.

Results::
The radioimmunoconjugate 90Y-DOTA-nimotuzumab was obtained with a radiochemical purity greater than
96%, and showed a good stability at 20°C as well as at 37°C in human plasma.

Conclusions::
The optimized conditions for a mild and easy preparation of 90Y-DOTA-nimotuzumab joined to a promising
stability under physiological conditions suggest to propose this radioimmunoconjugate as a potential diagnostic
radiopharmaceutical for β- radio-guided surgery.