bluuebunny/crossref_metadata_2025_split huggingface dataset:
Keap1-targeting microRNA-941 protects endometrial cells from oxygen and glucose deprivation-re-oxygenation by activating Nrf2 signaling
Authors: Li Shu-ping , Cheng Wei-nan , Li Ya , Xu Hong-bin , Li Ping , Zhang Deng-Xia , Han Hui 
Published: November 2019

Abstract
Background: Mimicking ischemia-reperfusion injury, oxygen and glucose deprivation (OGD)-re-oxygenation (OGDR) stimulation to endometrial cells induces significant oxidative stress and programmed necrosis, which can be inhibited by nuclear-factor-E2-related factor 2 (Nrf2) signaling activation. MicroRNA (miRNA)-induced silencing of the Nrf2 suppressor protein Keap1 is novel strategy to activate Nrf2 cascade. Methods: microRNA-941 (miR-941) expression was exogenously altered in HESC cells and primary human endometrial cells, and cells treated with OGDR. Nrf2 pathway genes were examined by Western blotting assay and real-time quantitative PCR analysis. Endometrial cell programmed necrosis and apoptosis were tested. Results: miR-941 is a novel Keap1-targeting miRNA, regulates Nrf2 signaling activation. In T-HESC cells and primary human endometrial cells, ectopic overexpression of miR-941 suppressed Keap1 3’-UTR (untranslated region) activity and downregulated its mRNA/protein expression, leading to Nrf2 cascade activation. Conversely, Keap1’s 3’-UTR activity and expression were elevated in endometrial cells with miR-941 inhibition, whereas Nrf2 activation was inhibited. miR-941 overexpression in endometrial cells largely attenuated OGDR-induced oxidative stress and programmed necrosis, both were intensified with miR-941 inhibition. Further studies show that Keap1-Nrf2 cascade activation is absolutely required for miR-941-induced endometrial cell protection. MiR-941 overexpression and inhibition were completely ineffective in Keap1-/Nrf2-KO T-HESC cells (using CRISPR/Cas9 strategy). Restoring Keap1 expression, by an UTR-depleted Keap1 construct, abolished miR-941-induced anti-OGDR activity in T-HESC cells. Conclusions: Targeting Keap1 by miR-941 activates Nrf2 cascade to protect human endometrial cells from OGDR-induced oxidative stress and programmed necrosis.
Recovery and stable persistence of chloroquine sensitivity in Plasmodium falciparum parasites after its discontinued use in Northern Uganda.
Authors: Balikagala Betty , Yatsushiro Miki Sakurai , Tachibana Shin-Ichiro , Ikeda Mie , Yamauchi Masato , Katuro Osbert T. , Ntege Edward Hosea , Sekihara Makoto , Fukuda Naoyuki , Takahashi Nobuyuki , Yatsushiro Shouki , Mori Toshiyuki , Hirai Makoto , Opio Walter , Obwoya Paul S. , Anywar Denis Arony , Auma Mary Alai , Palacpac Nirianne Marie Querijero , Tsuboi Takafumi , Odongo-Aginya Emmanuel Igwaro , Kimura Eisaku , Ogwang Martin David , Horii Toshihiro , Mita Toshihiro 
Published: November 2019

Abstract
Background Usage of chloroquine was discontinued from the treatment of Plasmodium falciparum infection in almost all endemic regions because of global spread of resistant parasites. Since the first report in Malawi, numerous epidemiological studies have demonstrated that the discontinuance led to re-emergence of chloroquine-susceptible P. falciparum parasites, suggesting a possible role in future malaria control. However, most studies were cross-sectional, with few studies looking at the persistence of chloroquine recovery in long term. This study fills the gap by providing, for a period of at least 6 years, proof of persistent re-emergence/stable recovery of susceptible parasite populations using both molecular and phenotypic methods Methods Ex vivo drug-susceptibility assays to chloroquine (n = 319) and lumefantrine (n = 335) were performed from 2013 to 2018 in Gulu, Northern Uganda where chloroquine had been removed from the official malaria treatment regimen since 2006. Genotyping of pfcrt and pfmdr1 was also performed. Results Chloroquine resistance (³100 nM) was observed in only 3 (1.3%) samples. Average IC50 values for chloroquine were persistently low throughout the study period (17.4–24.9 nM). Parasites harboring pfcrt K76 alleles showed significantly lower IC50s to chloroquine than the parasites harboring K76T alleles (21.4 nM vs 43.1 nM, p-value= 3.9×10-8). Prevalence of K76 alleles gradually increased from 71% in 2013 to 100% in 2018. Conclusion This study found evidence of stable persistence of chloroquine susceptibility with the fixation of pfcrt K76 in Northern Uganda after discontinuation of chloroquine in the region. Accumulation of similar evidence in other endemic areas in Uganda could open channels for possible future re-use of chloroquine as an option for malaria treatment or prevention.
Molecular surveillance of the Pfmdr1 N86Y allele in P. falciparum isolates from Brazzaville, Republic of Congo
Authors: Dossou-Yovo Louis Regis , Ntoumi Francine , Koukouikila-Koussounda Felix , Vouvoungui Jeannhey Christevy , Adedoja Ayodele , Nderu David , Velavan Thirumalaisamy P , Lenga Arsene 
Published: November 2019

Abstract
Background: Regular surveillance of artemisinin−based combination therapy tolerance or resistance molecular makers is vital for effective malaria treatment, control and eradication programmes. P. falciparum multiple drug resistance-1 gene (Pfmdr1) N86Y mutation is associated with reduced susceptibility to lumefantrine. This study assessed the prevalence of Pfmdr1 N86Y in Brazzaville, Republic of Congo. Methods: A total 1001 of P. falciparum−infected blood samples obtained from asymptomatic malaria pregnant women having a normal child delivery at the Madibou Integrated Health Center were analysed.Pfmdr1 N86Y genotyping was conducted using PCR-Restriction fragment length polymorphism (RFLP). Results: The wild type Pfmdr1 N86 allele was predominant (>68 %) in this study whereas a few isolates carrying the either the mutant allele (Pfmdr1 86Y) alone or both alleles (mixed genotype). The dominance of the wildtype allele (pfmdr1 N86) indicates the plausible decline P. falciparum susceptibility to lumefantrine. Conclusion: This study gives an update on the prevalence of Pfmdr1 N86Y alleles in Brazzaville, Republic of Congo. It also raises concern on the imminent emergence of resistance against artemether−lumefantrine in this setting. Our study underscores the importance to regular artemether−lumefantrine efficacy monitoring to inform malaria control programme of the Republic of Congo.
Cucuk Lampah: Cooperative Principles Violations to Create Laughter at Wedding Ceremony in Magetan
Authors: Mubarokah Qoniatul , Djatmika Djatmika , Sumarlam Sumarlam 
Published: November 2019

This research aimed at describing the violations of cooperative principles and the factors that created humor of Cucuk Lampah in the wedding ceremony in Magetan regency. This was descriptive qualitative research. The subjects of this research were all humor discourse conducted by Cucuk Lampah. Meanwhile, the objects were the data that contained the violation of the cooperative principle. The data collection used observation method with the tapping technique, then SBLC or Free Participant Observation technique, note-taking technique, and video recording technique. It used a pragmatic identity method based on utterances by heuristic technique to analyze data. The result shows that in creating humor, Cucuk Lampahmostly violates quantity maxim. It means that Cucuk Lampah prefers less and more information or contribution to the interaction. Cucuk Lampah is free to lie, using taboo, speaking indirectly with pambiwara, and singers. Cucuk Lampah also uses language play by mentioning the unexpected in the utterances to build up taboo words. The violations of the quality maxim, relevance maxim, and manner maxim are also done in less number compare to quantity maxim violations. The nonobservance of the maxims mostly is violating a maxim, flouting a maxim, infringing a maxim, suspending a maxim, and the last is opting out of a maxim
Firms` Participation in Tax Amnesty Program Engaged in Financial Reporting Manipulation: An Empirical Evidence from Listed Companies in Indonesia
Authors: Soepriyanto Gatot , Indra Yanto , The Olivia , Zudana Arfian 
Published: November 2019

The research investigated the relation between firms participated in tax amnesty programs and their tendency to manipulate financial statements. The research explored some unique research settings during Indonesia’s tax amnesty period in 2016-2017. To examine the association, the researchers employed Beneish’s M-Score model to categorize the firm’s tendency to manipulate its financial statements. As the test variable, it classified the firm’s participation in the tax amnesty program with a dummy variable, 1 if the firm participated, and 0 otherwise. To control the variations in financial statements manipulation, it also included firm size, leverage, and profitability in our empirical model. Based on the sample of 796 firm-year observations in the Indonesian Stock Exchange (IDX) from the 2012-2017 period, it is found some evidence that firms participate in tax amnesty programs do not engage in financial statements manipulation. Further analysis of the corporate tax avoidance measures shows that those firms do not engage in tax avoidance activities either. The results suggest that firms participate in the tax amnesty programs are not necessary ‘bad firms’, and they just participate as a ‘symbolic’ gesture to get some indirect benefits of the program.
Green Synthesis, Biological Activity Evaluation, and Molecular Docking Studies of Aryl Alkylidene 2, 4-thiazolidinedione and Rhodanine Derivatives as Antimicrobial Agents
Authors: Akhavan Malihe , Foroughifar Naser , Pasdar Hoda , Bekhradnia Ahmadreza 
Published: November 2019

Aim and Objective:
The magic scaffolds rhodanine and thiazolidine are very important
heterocyclic compounds in drug design and discovery. Those are important heterocyclic
compounds that have attracted a great deal of attention due to the fact that they exhibit a variety of
bioactivities including antibacterial, antifungal, antiviral, antimalarial, and anti-inflammatory
activities. These agents often exhibit selective toxicity. The goal of this study was molecular
docking, green and solvent-free efficient synthesis of a new series of hetero/aromatic substituted
rhodanine and thiazolidine analogues and then investigation of their antimicrobial activity.

Materials and Methods:
To a mixture of TZD or rhodanine (1 mmol) in the presence of ionic
liquid ChCl/urea, various aldehyde (1 mmol) was added. After completion of the reaction, obtained
crude compound was collected by filtration and products were recrystallized from ethanol. The
binding-free energy between all synthesized compounds with 3EEJ protein (C. glabrata enzyme)
were obtained by molecular docking studies. These compounds were evaluated using microdilution
method against (ATCC 6538) and (ATCC 12228) Gram-negative, (ATCC 8739) and (ATCC 9027)
as Gram-positive and (ATCC 1012), (ATCC 339), C. (ATCC 1057), (ATCC 503), (ATCC 340)
and (ATCC 194) as fungi.

Results:
All of the acceptable products were determined by 1H NMR, 13C NMR, Mas and FT-IR
spectroscopy. The binding-free energy between compounds 10a and 10b with 3EEJ protein were
found to be -8.08 kcal/mol and -8.15 kcal/mol, respectively. These compounds having a
heteroaromatic ring attached to the TZD or rhodanine core showed excellent antimicrobial activity
with MIC values of 0.25-8 μg/mL (compound 10a) and 0.5-16 μg/mL (compound 10b) against the
most tested fungi strains, Gram-positive and Gram-negative bacteria.

Conclusion:
A convenient and rapid method has been developed for the synthesis of rhodanine and
thiazolidine-2,4-dione (TZD) derivatives as efficient antimicrobial agents using a Deep Eutectic
Ionic Liquids (DEILs) choline chloride urea under solvent-free condition. Among the newly
synthesized compounds, (Z)-5-((quinoxalin-3-yl) methylene) thiazolidine-2, 4-dione (10a) and (Z)-
5- ((quinoxalin-3-yl) methylene)-2-thioxothiazolidin-one (10b) exerted the promising effect and
these compounds can be considered to be further probed as inhibitors of cgDHFR enzyme.
Potential Therapeutic Applications of C-Phycocyanin
Authors: Bannu Saira M. , Lomada Dakshayani , Gulla Surendra , Chandrasekhar Thummala , Reddanna Pallu , Reddy Madhava C. 
Published: November 2019

Background:Cancer and other disorders such as inflammation, autoimmune diseases and diabetes are the major health problems observed all over the world. Therefore, identifying a therapeutic target molecule for the treatment of these diseases is urgently needed to benefit public health. C-Phycocyanin (C-PC) is an important light yielding pigment intermittently systematized in the cyanobacterial species along with other algal species. It has numerous applications in the field of biotechnology and drug industry and also possesses antioxidant, anticancer, antiinflammatory, enhanced immune function, including liver and kidney protection properties. The molecular mechanism of action of C-PC for its anticancer activity could be the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells.Objectives:The current review summarizes an update on therapeutic applications of C-PC, its mechanism of action and mainly focuses on the recent development in the field of C-PC as a drug that exhibits beneficial effects against various human diseases including cancer and inflammation.Conclusion:he data from various studies suggest the therapeutic applications of C-PC such as anti-cancer activity, anti-inflammation, anti-angiogenic activity and healing capacity of certain autoimmune disorders. Mechanism of action of C-PC for its anticancer activity is the blockage of cell cycle progression, inducing apoptosis and autophagy in cancer cells. The future perspective of C-PC is to identify and define the molecular mechanism of its anti-cancer, anti-inflammatory and antioxidant activities, which would shed light on our knowledge on therapeutic applications of C-PC and may contribute significant benefits to global public health.
Molecular Mechanism of Resistance to Chemotherapy in Gastric Cancers, the Role of Autophagy
Authors: Spirina Liudmila V. , Avgustinovich Alexandra V. , Afanas’ev Sergey G. , Cheremisina Olga V. , Volkov Maxim Yu. , Choynzonov Evgeny L. , Gorbunov Alexey K. , Usynin Evgeny A. 
Published: November 2019

:
Gastric cancer (GC) is biologically and genetically heterogeneous with complex carcinogenesis
at the molecular level. Despite the application of multiple approaches in the GC treatment, its
5-year survival is poor. A major limitation of anti-cancer drugs application is intrinsic or acquired resistance,
especially to chemotherapeutical agents. It is known that the effectiveness of chemotherapy
remains debatable and varies according to the molecular type of GC. Chemotherapy has an established
role in the management of GC. Perioperative chemotherapy or postoperative chemotherapy is applied
for localized ones. Most of the advanced GC patients have a poor response to treatment and unfavorable
outcomes with standard therapies.

:
Resistance substantially limits the depth and duration of clinical responses to targeted anticancer therapies.
Through the use of complementary experimental approaches, investigators have revealed that
cancer cells can achieve resistance through adaptation or selection driven by specific genetic, epigenetic,
or microenvironmental alterations. Ultimately, these diverse alterations often lead to the activation
of MAPK, AKT/mTOR, and Wnt/β-catenin signaling pathways that, when co-opted, enable cancer
cells to survive drug treatments. We have summarized the mechanisms of resistance development
to cisplatin, 5-fluorouracil, and multidrug resistance in the GC management. The complexity of molecular
targets and components of signaling cascades altered in the resistance development results in
the absence of significant benefits in GC treatment, and its efficacy remains low. The universal process
responsible for the failure in the multimodal approach in GC treatment is autophagy. Its dual role
in oncogenesis is the most unexplored issue. We have discussed the possible mechanism of autophagy
regulation upon the action of endogenous factors and drugs. The experimental data obtained in the cultured
GC cells need further verification. To overcome the cancer resistance and to prevent autophagy
as the main reason of ineffective treatment, it is suggested the concept of the direct influence of autophagy
molecular markers followed by the standard chemotherapy. Dozen of studies have focused on
finding the rationale for the benefits of such complex therapy. The perspectives in the molecular-based
management of GC are associated with the development of molecular markers predicting the protective
autophagy initiation and search for novel targets of effective anticancer therapy.
The Posterior Perforated Substance: A Brain Mystery Wrapped in an Enigma
Authors: Nikolenko Vladimir N. , Gridin Leonid A. , Oganesyan Marine V. , Rizaeva Negoriya A. , Podolskiy Yury S. , Kudryashova Valentina A. , Kochurova Ekaterina V. , Kostin Roman K. , Tyagunova Ekaterina E. , Mikhaleva Liudmila M. , Avila-Rodriguez Marco , Somasundaram Siva G. , Kirkland Cecil E. , Aliev Gjumrakch 
Published: November 2019

Background:
There is a dearth of published information on the posterior perforated substance
as compared to the anterior perforated substance. We managed to glean facts about the posterior perforated
substance that can serve as a landmark for surgical operations in the adjacent regions of the midbrain
and the vessels passing through it. Moreover, the posterior perforated substance contains the interpeduncular
nucleus responsible for the mental state of the individual.

Objectives:
1) To describe the topography of the blood vessels supplying the posterior perforated substance
area from the surgical point of view; 2) to investigate the functions of the interpeduncular nucleus.

Methods:
We assembled and analyzed results from source databases by Elsevier, NCBI MedLine, Scopus,
Scholar. Google and Embase. Each article was studied in detail for practically useful information
about the posterior perforated substance.

Results:
The P1-segment perforating branches of the posterior cerebral artery supply the posterior perforated
substance. This area is especially vulnerable in the case of vascular pathologies. The posterior
communicating artery can block the surgeon’s view and impede maneuverability of the tool in the area
of the posterior perforated substance, which may be addressed using the separation technique, which can
lead to positive results. In addition, the medial habenula-interpeduncular nucleus in the posterior perforated
substance is associated with various addictions and psychiatric conditions.

Conclusions:
The posterior perforated substance area is of great interest for surgical interventions. Future
studies of the interpeduncular nucleus anticipate the development of drugs to affect different types of
dependencies and some mental diseases.
Presynaptic Release-regulating Metabotropic Glutamate Receptors: An Update
Authors: Olivero Guendalina , Vergassola Matteo , Cisani Francesca , Roggeri Alessandra , Pittaluga Anna 
Published: November 2019

:
Metabotropic glutamate (mGlu) receptors represent the largest family of glutamate receptors in
mammals and act as fine tuners of the chemical transmission in central nervous system (CNS).

:
In the last decade, results concerning the expression and the subcellular localization of mGlu receptors
further clarified their role in physio-pathological conditions. Concomitantly, their pharmacological
characterization largely improved thanks to the identification of new compounds (chemical ligands
and antibodies recognizing epitopic sequences of the receptor proteins) that allowed to decipher the
protein compositions of the naive receptors.

:
mGlu receptors are expressed at the presynaptic site of chemical synapses. Here, they modulate
intraterminal enzymatic pathways controlling the migration and the fusion of vesicles to synaptic
membranes as well as the phosphorylation of colocalized receptors. Both the control of transmitter
exocytosis and the phosphorylation of colocalized receptors elicited by mGlu receptors are relevant
events that dictate the plasticity of nerve terminals, and account for the main role of presynaptic
mGlu receptors as modulators of neuronal signalling.

:
The role of the presynaptic mGlu receptors in the CNS has been the matter of several studies and
this review aims at briefly summarizing the recent observations obtained with isolated nerve endings
(we refer to as synaptosomes). We focus on the pharmacological characterization of these receptors
and on their receptor-receptor interaction / oligo-dimerization in nerve endings that could be
relevant to the development of new therapeutic approaches for the cure of central pathologies.
Survey of Pretreatment HIV Drug Resistance and Genetic Transmission Network Analysis Among HIV Patients in a High Drug-Use Area of Southwest China
Authors: Liu Lei , Dong Aobo , Liao Lingjie , Feng Yi , Shao Yiming , Liang Shu , Ruan Yuhua , Xing Hui 
Published: November 2019

Background:
Pretreatment drug resistance (PDR) poses an increasing threat to the success
of antiretroviral treatment (ART) programs in China. We aimed to conduct a survey of PDR
among HIV patients in an area in Southwest China with extensive drug trafficking.

Methods:
Consecutive cross-sectional surveys were conducted in Liangshan Prefecture of Sichuan
Province from 2009 to 2018 based on the WHO-recommended method. PDR was identified by testing
pol region sequences with the Stanford HIVdb algorithm (version 7.0). PDR prevalence and related
factors were assessed by multivariable logistic regression. The transmission of HIV drug resistance
was analyzed using a genetic transmission network.

Results:
HIV-1 pol genes from 1889 patients were successfully amplified. The distribution of HIV-
1 genotypes was as follows: CRF07_BC (94.0%), CRF08_BC (2.3%), CRF01_AE (2.0%) and others
(1.4%). Of the participants, 6.9% (95% CI: 4.1-8.1%) had pretreatment resistance to 12 antiretroviral
drugs recommended by the WHO, and nucleoside reverse transcriptase inhibitor (NRTI),
non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitors (PI) resistance were
identified among 1.4% (95% CI: 0.7-3.4%), 5.8% (95% CI: 1.2-8.7%) and 0.4% (95% CI: 0.1-
3.0%) of the patients, respectively. In the multivariate logistic model, the prevalence of PDR was
1.52-fold higher among intravenous drug users (IDUs) than among patients infected by heterosexual
transmission (95% CI: 1.07-2.38; P=0.049), and the prevalence of PDR among patients diagnosed
from 2017-2018 was 2.03-fold higher than that among patients diagnosed from 2009-2016 (95% CI:
1.18-5.76; P=0.018). A total of 26 clusters containing PDR and a rapidly growing drug resistancerelated
cluster containing the E138Q and V179D mutations were identified by genetic transmission
network analysis.

Conclusions:
The results show a moderate overall level of PDR prevalence and rapidly growing
drug resistance over time. Preventive intervention should be focused on controlling the HIV epidemic
among drug users, and surveillance is urgently needed to monitor the trend of PDR.