bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lepidine B from Lepidium sativum Seeds as Multi-Functional Anti- Alzheimer’s Disease Agent: In Vitro and In Silico Studies
Authors: Talia Serseg , Benarous Khedidja , Lamrani Meriem , Yousfi Mohamed 
Published: March 2020

Objective:
The present study is carried out to screen the anticholinesterase effect of the
total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B & E to inhibit
AChE, BuChE, BACE, and MAGL. Hence, determining the main interactions in the inhibitorenzyme
complex.

Methods:
Inhibitory effect of Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus extracts
on acetylcholinesterase using the Ellman method was investigated with Donepezil as the
positive control. A molecular docking study is achieved using Autodock Vina. The structures of
target molecules Lepidine B & E and the four enzymes were obtained from the PubChem database
and Protein databank.

Results:
Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea
and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of
0.59 ± 0.04, 0.57 ± 0.00 and 0.49 ± 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as a
positive control. The major components of alkaloids of L. sativum, Lepidine B & E bind tightly to
AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a noncompetitive
inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent
the HuAChE-induced Aβ aggregation. All the complexes of Lepidine B & E with the four enzymes
show significant, several and different interactions.

Conclusion:
Our current study indicates that Lepidine B & E are promising anti-AD drugs and
might become drug candidates to prevent Alzheimer's disease due to their multiple roles as potent
inhibitors for AChE, BuChE, BACE, and MAGL. Indeed, they could inhibit Aβ fibrillogenesis. No
previous results about the inhibitory effect of Lepidine B & E on the AChE, BuChE, β secretase,
and monoacylglycerol lipase were reported.
Is Intraoperative Opioids Avoidance A Utopia? A Matched Study in Laparoscopic Hysterectomy
Authors: Forget Patrice , De Kock Marc , Lovqvist Linda , Lois Fernande 
Published: March 2020

Background:
Opioid-sparing strategies are recommended, and Opioid-Free Anaesthesia
(OFA) is proposed in the literature. But few data exist about the feasibility of OFA in the routine
practice. From a larger series of 21,463 patients receiving OFA, this work investigates the postoperative
pain and related outcomes in patients undergoing laparoscopic hysterectomy.

Materials and Methods:
This matched retrospective study concerned 521 patients scheduled for a
laparoscopic hysterectomy between 2010 and 2015 (118 receiving OFA and 403 receiving anaesthesia
with opioids, AO). Primary outcome was pain in the Post-Anaesthetic Care Unit (PACU).

Results:
Among the 521 included patients, 403 received sufentanil (mean±SD: 0.1±0.05 mcg/kg),
the only synthetic opioid used to balance anaesthesia. Concerning the 118 patients receiving OFA,
most of them received an association of clonidine (97%) and ketamine (95%). Most of the patients
in both groups received non-steroidal anti-inflammatory drugs. No difference in pain scores was
observed between AO and OFA (median [IQR], respectively: 4 [0-5] vs. 4.5 [0-6], P=0.74). A difference
in the perioperative morphine equivalent use was observed (mean±SD: 0.18±0.06 mg/kg vs.
0.09±0.06 mg/kg, P<0.001). No difference was observed regarding the nausea/vomiting incidences,
use of anti-emetics, sedation scores, or time spent at the PACU.

Conclusions:
Coming from an extensive daily practice, these data show that OFA is feasible and not
associated with higher pain scores or longer PACU stay, suggesting the absence of specific immediate
complications.
Feasibility of Repurposing Clioquinol for Cancer Therapy
Authors: Khan Raheel , Khan Harras , Abdullah Yassen , Dou Q. Ping 
Published: March 2020

Background:
Cancer is a prevalent disease in the world and is becoming more widespread as
time goes on. Advanced and more effective chemotherapeutics need to be developed for the treatment
of cancer to keep up with this prevalence. Repurposing drugs is an alternative to discover new chemotherapeutics.
Clioquinol is currently being studied for reposition as an anti-cancer drug.

Objective:
This study aimed to summarize the anti-cancer effects of clioquinol and its derivatives
through a detailed literature and patent review and to review their potential re-uses in cancer treatment.

Methods:
Research articles were collected through a PubMed database search using the keywords
“Clioquinol” and “Cancer.” The keywords “Clioquinol Derivatives” and “Clioquinol Analogues” were
also used on a PubMed database search to gather research articles on clioquinol derivatives. Patents
were gathered through a Google Patents database search using the keywords “Clioquinol” and “Cancer.”

Results:
Clioquinol acts as a copper and zinc ionophore, a proteasome inhibitor, an anti-angiogenesis
agent, and is an inhibitor of key signal transduction pathways responsible for its growth-inhibitory activity
and cytotoxicity in cancer cells preclinically. A clinical trial conducted by Schimmer et al., resulted
in poor outcomes that prompted studies on alternative clioquinol-based applications, such as new
combinations, new delivery methods, or new clioquinol-derived analogues. In addition, numerous patents
claim alternative uses of clioquinol for cancer therapy.

Conclusion:
Clioquinol exhibits anti-cancer activities in many cancer types, preclinically. Low therapeutic
efficacy in a clinical trial has prompted new studies that aim to discover more effective clioquinol-
based cancer therapies.
Increased NID1 Expression among Breast Cancer Lung Metastatic Women; A Comparative Analysis between Naive and Treated Cases
Authors: Urooj Tabinda , Wasim Bushra , Mushtaq Shamim , Haider Ghulam , Shah Syed N.N. , Ghani Rubina , Qureshi Muhammad F.H. 
Published: March 2020

Background:Lungs are the second most common reported site of distant metastasis in Breast cancer after bone. Mostly the studies were conducted in cell lines and animal model. To date, there is no blood biomarker reported that could determine the breast cancer progression in terms of lung metastasis.Objective:The aim of this study is to determine Nidogen-1 (NID1)’s mRNA and protein expressions in non-invasive blood samples of breast cancer, in early (II) and lung metastasis advanced stages (III & IV) of naive and treated groups. To determine the functional association of NID1, we employed an in silico analysis, STRING database version 11.Methods:A total of n = 175 cases of breast cancer were recruited in our study. Real time quantitative PCR and ELISA were performed to analyze the mRNA and protein expressions of NID1 respectively. An in silico method is also used to assess NID1’s interactome. Some significant patents related to this topic were also studied and discussed in this research paper.Results:The results show high levels of NID1’s mRNA in the naive group (Group A) as compared to treated group (Group B). Similar trend of increased NID1’s protein expressions was also observed among naive and treated groups, respectively. Our results also show the significant impact of treatment on NID1’s gene and protein expressions. In silico analysis has revealed the functional association of NID1 with its different interactome protein partners.Conclusions:The increased expression of NID1 in early to advanced naive as compared to the treated groups with lung metastasis makes it a promising marker which has pro-metastatic role in breast cancer.
Beta-Caryophyllene Suppresses Ovarian Cancer Proliferation by Inducing Cell Cycle Arrest and Apoptosis
Authors: Arul Santhosh , Rajagopalan Harinee , Ravi Jivitesh , Dayalan Haripriya 
Published: March 2020

Background:
Ovarian cancer is the fifth most common cause of cancer deaths among women with
lesser prognostics. Current treatment options are chemotherapy with platinum and taxane based chemotherapy.
β-Caryophyllene (BCP) an essential oil found in many plant species is known to possess an anti-proliferative
effect.

Objective:
We aimed to investigate the antiproliferative, cytotoxic, and apoptotic role of BCP against ovarian
cancer cells PA-1 and OAW 42.

Methods:
The antiproliferative effect of BCP was determined by MTT assay and cell viability by trypan blue
exclusion assay. Cell cycle and live/dead cell analyses were performed by flow cytometry to determine cell
cycle distribution and apoptosis, respectively.

Results:
Results of MTT assay proved the anti-proliferative effect of BCP in a dose and time-dependent manner
in ovarian cancer cells. Cell cycle analysis showed that BCP induced S Phase arrest in OAW 42 cells. Results of
apoptosis assay confirmed the apoptosis inducing potential of BCP in ovarian cancer cells. The apoptosis is
mediated by caspase-3 activation and PARP cleavage.

Conclusion:
The results of our present study prove that BCP exerts its action partly by inducing cell cycle arrest
and apoptosis in ovarian cancer. We conclude that BCP is a potential anti-cancer agent.
Hybrids of Quinoline and Anilinopyrimidine: Novel EGFRT790M Inhibitors with Antiproliferative Activity against Non-Small Cell Lung Cancer Cell Lines
Authors: Han Chun , Ren Jiahong , Su Feng , Hu Xiaoqin , Li Mengyao , Wang Zhijun , Wu Lintao 
Published: March 2020

Background:
The third-generation irreversible Epidermal Growth Factor Receptor (EGFR) Tyrosine
Kinase Inhibitors (TKIs) inhibit the T790M mutation while sparing EGFRWT. However, the C797S point mutation
confers resistance to existing irreversible EGFRT790M inhibitors.

Objective:
Novel EGFRT790M inhibitors were designed through hybridization of quinoline and anilinopyrimidine,
and biologically evaluated their antiproliferative activity against Non-Small Cell Lung Cancer (NSCLC) cell
lines.

Methods:
The target compounds 11a-h were synthesized and structurally characterized with 1H, 13C Nuclear
Magnetic Resonance (NMR) spectroscopy and High-Resolution Mass Spectrometry (HRMS). Their inhibitory
effects on tumor cell proliferation and EGFR kinase were biologically evaluated. Additionally, molecular docking
studies were also performed on the representative typical EGFRT790M inhibitor.

Results:
Most of the evaluated compounds displayed moderate antiproliferative activity on H1975 cells with
EGFRL858R/T790M. However, compound 11a (IC50 = 2.235 ± 0.565μM) showed stronger inhibition than gefitinib
(IC50 = 8.830 ± 0.495μM) in concentration- and time-dependent manner. Moreover, compound 11a exhibited
weaker inhibitory activities on cells with EGFRWT. Specifically, compound 11a strongly suppressed
EGFRL858R/T790M (IC50 = 0.515 ± 0.011μM) relative to EGFRWT (IC50 = 0.913 ± 0.068μM). Furthermore, molecular
docking studies demonstrated its strong binding contacts with the EGFRT790M enzyme through hydrogen
bonds and other non-bonded interactions.

Conclusion:
Taken together, these results indicate that the hybrid of quinoline and anilinopyrimidine 11a, could
be a potential inhibitor of EGFRT790M in NSCLC, which warrants further in-depth studies.
VALIDATED KINETIC SPECTROPHOTOMETRIC DETERMINATION OF PITAVASTATIN CALCIUM USING ACIDIC PERMANGANATE OXIDATION
Authors: JAMAL MARWA K. A. L. 
Published: March 2020

Objective: Development and validation of a sensitive, indirect spectrophotometric kinetic method, based on oxidation-reduction reaction, using potassium permanganate, for the quantitative assay of pitavastatin calcium, a cardiovascular drug used for the treatment of hyperlipidemia.
Methods: The developed spectrophotometric kinetic method is based on the ability of potassium permanganate to oxidize Pitavastatin, where, the drug solution is treated with a fixed concentration of permanganate in acidic medium, and after a specified time, the unreacted permanganate is measured at 525 nm. All variables affecting the color development have been investigated and the conditions were optimized. Different kinetic methods, including initial rate, rate constant, fixed time and fixed concentration, were applied for the determination Pitavastatin.
Results: During the course of the reaction, the absorbance values, at 525 nm, related to KMnO4, decreased linearly with increasing the concentration of the drug. The reaction rate obeyed was found to be pseudo-first-order and the kinetic method used was the fixed-time method. The assay of PITA in the concentration range of 16-80 μg/ml, using the fixed time method was successfully determined with a correlation coefficient value of 0.9999. The applicability of the developed method was also demonstrated by the determination of pitavastatin in its pure form and in its pharmaceutical formulation, where, the effect of excipients has also been studied and found to have no effect.
Conclusion: The developed indirect spectrophotometric kinetic method, using the fixed time method, was used for the determination of Pitavastatin in pharmaceutical tablets. This method was simple, accurate and easy to apply for routine assay and in quality control laboratories.
CYTOTOXIC METABOLITES OF ALTERNARIA ALTERNATA, AN ENDOPHYTE OF THE MEDICINAL PLANT BIDENS BIPINNATA
Authors: ABDOU RANDA , DAWOUD MOHAMED 
Published: March 2020

Objective: Endophytes are widely spread in the plant kingdom and represent a very promising source of biologically active natural products. The medicinal plant Bidens bipinnata Lin. (Asteraceae) which is known for its anti-inflammatory, antifungal and antitumor effects has been chosen for the investigation of its endophyte to search for bioactive metabolites.
Methods: An endophytic Alternaria alternata species was isolated from the leaves of the plant B. bipinnata Lin. To investigate the metabolic profile of this endophytic fungus it was cultivated in several culture media as static and shaken culture. The antimicrobial and cytotoxic activities of the ethyl acetate extracts of the fungus were examined. Extracts exhibiting highest antimicrobial activities in agar diffusion assay and cytotoxicity against HeLa cancer cell line were subjected to activity-guided chromatographic fractionation for the identification of bioactive metabolites. A cytotoxic assay was performed on the isolated compounds against HeLa cancer cell lines as well as cytostatic activity tests against HUVEC and K-562 cell lines.
Results: Chromatographic fractionation resulted in the isolation and identification of alternariol and tentoxin from the extract of the fungus cultivated in medium M5 while sterigmatocystin was isolated in addition to alternariol and tentoxin from the extract of the fungus grown in medium M25. Both alternariol and sterigmatocystin proved to be of moderate cytotoxicity and weak cytostatic activity with alternariol showing higher cytotoxic activity than sterigmatocystin. Highest cytotoxicity against HeLa cell lines was observed for tentoxin with a CC50 of 22.5 µg/ml.
Conclusion: This study presents the isolation and identification of the bioactive metabolites alternariol, sterigmatocystin and tentoxin from the endophyte A. alternata in addition to the antifungal activity of the strain extract as well as the cytotoxic and cytostatic activities of the isolated metabolites against HeLa, HUVEC and K-562 cell lines, respectively.
HAART THERAPY IN GHANA: COMPARATIVE ASSESSMENT OF THE EFFECTIVENESS OF DIFFERENT HAART COMBINATIONS AT KOMFO ANOKYE TEACHING HOSPITAL
Authors: GYAMFI PAA KOFI TAWIAH ADU , MENSAH KWESI BOADU , ARHIN STEPHEN MENSAH , MOOMIN ALIU 
Published: March 2020

Objective: Although all marketed antiretrovirals (ARVs) have proven efficacy, genetic differences can result in varied effectiveness. This study was conducted to determine the effectiveness of different Highly Active Antiretroviral Therapy (HAART) combinations among patients attending HIV clinic at a Major Teaching Hospital in Ghana.
Methods: The study was a retrospective study involving 500 patients at an HIV clinic in the Ashanti Region of Ghana.
Results: Twelve major antiretroviral combinations for HAART were prescribed at the study center. The most prescribed drug combinations were AZT+3TC+EFV and AZT+3TC+NVP. The study identified that HAART, irrespective of the kind of drug combination used, was effective at increasing CD4 count within the first 6 mo of therapy initiation in the study population. However, the magnitude of the increases differed from combination to combination. All HAART combinations with zidovudine as one of the drugs resulted in higher CD4 counts compared with combinations containing stavudine. HAART with nevirapine also resulted in a higher CD4 count than those with efavirenz. However, efavirenz-based combinations appeared to be more effective in critically ill patients and patients with mean CD4+T helper cells count below 100 cell/mm3. More importantly, efavirenz was common among all HAART combinations that resulted in treatment failure.
Conclusion: There was significant variation in response to different HAART combination among Ghanaian HIV patients. However, there was no statistically significant difference in mean CD4 count between the two most predominately used HAART i. e AZT+3TC+EFV and AZT+3TC+NVP.
Análise da atenção farmacêutica prestada aos clientes idosos hipertensos atendidos em uma drogaria na Cidade do Recife
Authors: Vieira dos Santos Josiane , Sousa Da Silva José Orlando , Apolinário Filho Maurilucio , Pontes de Oliveira Barros Danilo , De Oliveira Filho João José , Torres Santos Manuella Alexandre , Moura Boaviagem Karinna , Calazans Silva de Amorim Ray 
Published: March 2020

Introdução: A Hipertensão Arterial Sistêmica (HAS) constitui um grave problema de saúde pública de alta prevalência e de causas multifatoriais. Em 95% dos casos, não possui uma causa identificável. Os indivíduos que apresentam a doença são frequentemente assintomáticos, o que a define como uma patologia de característica silenciosa e perigosa. Desta forma, é caracterizada como fator de risco para o desenvolvimento de doenças cardiovasculares. Atualmente, a HAS é responsável por 9,4 milhões de óbitos no mundo, chegando a 30% em adultos brasileiros. Os idosos são os mais diagnosticados com HAS, correspondendo a 50% dos casos no Brasil. Objetivo: O interesse da pesquisa é analisar o serviço de atenção farmacêutica oferecida, através do consultório farmacêutico aos idosos hipertensos atendidos em uma drogaria na cidade do Recife. Metodologia: Trata-se de um estudo descritivo com abordagem quantitativa, na qual se propôs a avaliar o serviço de atenção farmacêutica. O estudo utilizou dados secundários dos clientes idosos hipertensos com 60 anos ou mais atendidos no consultório farmacêutico, no período de fevereiro a abril de 2018. Resultados: O trabalho teve sua importância, pois, quando não tratada, a hipertensão arterial sistêmica pode levar a complicações como infarto agudo do miocárdio, acidente vascular encefálico, insuficiência renal, maiores taxas de hospitalização e mortalidade. Esta pesquisa mostrou que: dos 200 idosos avaliados, 136 (68%) são do sexo feminino; em relação aos anti-hipertensivos mais utilizados, a losartana potássica teve o maior percentual com 64%; demonstrou ainda que 80,5% não praticam atividades físicas regularmente; e o consumo de bebidas alcóolicas está presente em 13% dos idosos. Um dos maiores desafios está relacionado ao seguimento da terapia prescrita, pois, apesar de possuírem conhecimento sobre a patologia, 119 (59%) não fazem acompanhamento contínuo no serviço de atenção farmacêutica. Conclusão: Os achados indicam a necessidade de controle da HAS através da mudança no estilo de vida com práticas regulares de atividades físicas e aderência ao tratamento prescrito. Portanto, o serviço de atenção farmacêutica ofertado em drogarias se faz de suma importância, uma vez que o profissional farmacêutico poderá fornecer subsídios, por meio de ações educativas e orientações sobre o regime terapêutico, através do acompanhamento e incentivo, quanto aos hábitos saudáveis e ao uso correto dos medicamentos prescritos pelo profissional médico.
Fatores de risco para o desenvolvimento de infecções fúngicas sistêmicas em pacientes internados em Unidade de Terapia Intensiva
Authors: Mares Brasileiro Pessoa Stela , Cintra de Queiroz Medeiros Carolina , Porto Almeida Jamile , Mistro Sóstenes 
Published: March 2020

Introdução: As infecções fúngicas invasivas (IFI’s) em pacientes de unidade de terapia intensiva (UTI) representam um importante fator de mortalidade e estão associados à presença de fatores de risco. Esses fatores podem ser uso de antibiótico de amplo-espectro, corticosteroides, imunossupressores, intubação orotraqueal (IOT), cateter venoso central (CVC), hemodiálise, cirurgia abdominal, infecção pelo vírus HIV, entre outros. A alta taxa de mortalidade está relacionada principalmente a dificuldade na realização do diagnóstico precoce e a identificação dos fatores de risco pode guiar o início da terapia antifúngica, o que pode reduzir os danos causados aos pacientes. Objetivo: O objetivo deste estudo foi avaliar a relação entre a presença de fatores de risco para IFI’s e o início da terapia antifúngica em pacientes internados na UTI. Metodologia: Trata-se de uma coorte baseada em dados retrospectivos em um Hospital Público localizado no interior da Bahia. Foram avaliados todos os pacientes adultos internados na UTI entre janeiro de 2014 a setembro de 2015. A associação entre a presença dos fatores de risco e a introdução do antifúngico foi analisada no modelo bivariado com determinação do risco relativo. As variáveis com associação positiva (p<0,05) foram inseridas em um modelo multivariado, com regressão de Poisson a fim de identificar a força da associação de cada um deles com o desfecho avaliado. Resultados: Foram internados 572 pacientes na UTI durante o período do estudo, dos quais 447 preencheram os critérios de inclusão. Desse total, 59 (13,2%) utilizaram terapia antifúngica em algum momento durante a internação. Foram identificados 9 fatores de risco na população estudada. Desses, o uso de antibioticoterapia de amplo-espectro, realização de cirurgia abdominal, hemodiálise, infecção pelo vírus HIV e uso de nutrição parenteral apresentaram associ ação estatisticamente significante com a indicação da terapia antifúngica. Conclusão: No presente estudo, foi identificada uma forte associação entre a presença de fatores de risco para o desenvolvimento IFI’s e a introdução da terapia antifúngica. A associação observada se deve principalmente ao uso de antibióticos de amplo-espectro, realização de hemodiálise, ter sido submetido recentemente a cirurgia abdominal ou infecção pelo vírus HIV.
El carnaval en la obra El público de Lorca
Authors: Mendoza Zazueta Juan Enrique 
Published: March 2020

La meta del presente trabajo es distinguir los diferentes niveles dramáticos que componen El público de Federico García Lorca. Para ello se utilizará la edición prologada por el doctor Huerta Calvo (2006). A la par de los comentarios sobre los niveles dramáticos, se intentará relacionar con el sentido transgresor carnavalesco y la estructura del texto dramático. Para ello nos valdremos de autores como Julio Huélamo Kosma (1996) para la interpretación y de José Luis García Barrientos (2012) para el análisis de los niveles dramáticos del texto, que nos ayuden a relacionarla con el tema propuesto por el autor.