bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quinolone Congeners As Mammalian Topoisomerase-11 Inhibitors
Authors: Radl Stanislav , Daxt Scott 
Published: February 2022

Abstract:
The development of the quinolone antibacterials has clearly demonstrated that inhibition of topoisomerase activity can constitute an effective means by which to induce selective pathogen cell death. These agents disrupt normal bacterial gyrase protein-DNA substrate interactions and lead to the formation of a ternary "cleavable complex" which results in a bactericidp.l therapeutic mode of action. However, certain structural 'subsets'
of quinolones have been shown to be toxic to mammalian cells as a result of competing inhibition of mammalian topoisomerase II activity. The investigation of these congeners has revealed that rather simple molecular modifications to the basic quinolone pharmacophore can potentiate activity against mammalian proteins. Structure-activity relationships have been elucidated in an attempt to selectively target the action of mammalian topoisomerase as a means for anticancer chemotherapy.
Inhibitors of Cyclooxygenase and 5-Lipoxygenase
Authors: Mantri Padmaja , Witiak Donald T. 
Published: February 2022

Abstract:
Prostaglandin H synthase (PGH synthase) and 5-Lipoxygenase (5-LO) are important enzymes that catalyze the formation of putative intermediates involved in the inflammatory process. The mechanism by which PGH synthase and 5-LO convert their common substrate arachidonic acid (AA) into prostaglandins, thromboxanes and leukotrienes is discussed. Recent advances on competitive, mechanism-based and reversible non­ competitive inhibitors of PGH synthase are described. Further discussed are
classes of compounds which inhibit 5-LO, including compounds structurally related to 5-LO substrate or product, agents acting on 5-LO activating protein (FLAP), iron chelators and antioxidants.
β-Aianyi-L-histidinato Zinc: A Potent Activator in Bone Formation
Authors: Yamaguchit Masayoshi 
Published: February 2022

Abstract:
It is known that zinc is essential for the growth of human and many animals. Bone has one of the highest zinc concentrations of all tissues. Bone growth retardation is a common finding in various conditions associated with zinc deficiency, seggesting a physiological role of zinc in the growth and calcification of bone tissue. Bone zinc content is decreased by development with aging, skeletal unloading and postmenopausal conditions. Thus zinc deficiency may play a pathophysiological role in the deterioration of bone metabolism. In fact, zinc has been demonstrated to
have a stimulatory effect on bone formation and mineralization due to promoting bone cellular protein synthesis. AHZ is a new zinc compand, in which zinc is chelated to -alanyi-L­ histidine (L-carnosine). This compound can stimulate bone formation and mineralization in weanling and aged rats, and it has a direct anabolic effect in culture system of bone tissue and bone-forming cells (osteoblastic cells). The stimulatory effect of AHZ on bone formation was more intensive than that of zinc sulfate, showing that the mode of AHZ action differs from that of zinc sulfate. AHZ has a stimulating effect on proliferation and differentiation in osteoblastic cells due to a newly synthesized protein components. It is confirmed that bone-forming effect of AHZ is a greater than that of various bone-regulating hormones and other factors. The oral administration of AHZ has a fine restorative effect on osteopenia with various pathophysiological conditions. AHZ may be new drug in therapy of osteoporosis. Clinical studies are in progress.
Glyceride Conjugates as Drug Carriers
Authors: Lambert D. M. , Scriba G. K.  E. , Gallez B. , Poupaert J.  H. , Dumont P. 
Published: February 2022

Abstract:
Drug-lipid conjugates have been prepared in order to confer the attached drugs to the metabolic pathways of natural lipids. The drug can be covalently bound either to a fatty acid or to a glyceride. In glycerides, one or two fatty acid moieties have been replaced by a drug realizing pseudoglycerides. These pseudoglycerides exhibited some physicochemi­
cal properties and absorption characteristics similar to those of natural triglycerides resulting in a different pharmacokinetic and/or pharmacodynamic profile compared that of the parent drug. Non-steroidal anti-inflammatory drugs such as aspirin, indomethacin, ibuprofen, naproxen and aclofenac were covalently bound to diglycerides in order to reduce the ulcerogenicity of the compounds. Employing the absorption process of dietary fat, pseudoglycerides have been used for the targeting of the lymphatic route in order to avoid the first-pass metabolism of a drug (L-DOPA) and I or to target the lymphatic system for the treatment of lymphatic metastasis (chlorambucil, melphalan) or filiariasis (melphalan and GABA). Pseudoglycerides and other glyceride-like structures have been evaluated in order to increase the intestinal absorption of poorly water-soluble drugs such as phenytoin. An improvement of the blood-brain barrier penetration of GABA covalently bound to glycerides has been reported in the 80's, A similar approach was followed for L-dopa, glycine, valproate, and the enkephalinase inhibitor thiorphan including amide bio-isosteres of glycerides. Radioiodinated agents containing fluoride and nitroxyl moieties were coupled to glycerides and fatty acids as potential hepatographic agents in
nuclear medicine, 19F- and 1H-nuclear magnetic resonance imaging, respectively. A variety of phospholipid-linked cytotoxic nucleosides and nucleoside analogues such as ara-C, AZT and acyclovir have been prepared. Compared to the parent drugs the phospholipid analogs exhibited increased antineoplastic activity in vitro and in vivo. The conjugates were also active against tumors and viruses that were resistant against the drug itself.
Sanguinarine Represses the Growth and Metastasis of Non-small Cell Lung Cancer
by Facilitating Ferroptosis
Authors: Xu Rongzhong , Wu Jianchun , Luo Yingbin , Wang Yuli , Tian Jianhui , Teng Wenjing , Zhang Bo , Fang Zhihong , Li Yan 
Published: February 2022

Aim of the study:
Ethnopharmacological relevance: Sanguinarine (SAG), a natural benzophenanthridine
alkaloid derived from the root of Sanguinaria canadensis Linn. (Bloodroot), possesses a potential anticancer
activity. Lung carcinoma is the chief cause of malignancy-related mortality in China. Non-small cell lung carcinoma
(NSCLC) is the main subtype of lung carcinoma and accounts for about eighty-five percent of this disease.
Current treatment in controlling and curing NSCLC remains deficient.

Aim:
The role and underlying mechanism of SAG in repressing the growth and metastasis of NSCLC were
explored.

Materials and Methods:
The role of SAG in regulating the proliferation and invasion of NSCLC cells was
evaluated in vitro and in a xenograft model. After treatment with SAG, Fe2+ concentration, reactive oxygen species
(ROS) levels, malondialdehyde (MDA), and glutathione (GSH) content in NSCLC cells were assessed to
evaluate the effect of SAG on facilitating ferroptosis.

Results:
SAG exhibited a dose- and time-dependent cytotoxicity in A549 and H3122 cells. SAG treatment
effectively repressed the growth and metastasis of NSCLC in a xenograft model. We, for the first time, verified
that SAG triggered ferroptosis of NSCLC cells, as evidenced by increased Fe2+ concentration, ROS level, and
MDA content, and decreased GSH content. Mechanistically, SAG decreased the protein stability of glutathione
peroxide 4 (GPX4) through E3 ligase STUB1-mediated ubiquitination and degradation of endogenous GPX4.
GPX4 overexpression restored the proliferation and invasion of NSCLC cells treated with SAG through inhibiting
ferroptosis.

Conclusions:
SAG inhibits the growth and metastasis of NSCLC by regulating STUB1/GPX4-dependent
ferroptosis.
Venous Thromboembolism Following Major Abdominal Surgery for Cancer: A
Guide for the Surgical Intern
Authors: Theochari Christina A. , Theochari Nikoletta A. , Mylonas Konstantinos S. , Papaconstantinou Dimitrios , Giannakodimos Ilias , Spartalis Eleftherios , Patelis Nikolaos , Schizas Dimitrios 
Published: February 2022

Background:
Venous thromboembolism (VTE) is a term used to compositely describe deep vein
thrombosis (DVT) and pulmonary embolism (PE). Overall, the incidence of VTE after major abdominal and
pelvic surgery has been reported to be between 10% and 40%.

Objective:
The aim of this study is to estimate the incidence of post-operative VTE in patients undergoing major
abdominal surgery for cancer, to identify risk factors associated with VTE, and to assess available thromboprophylaxis
tools.

Methods:
A Medline and Cochrane literature search from database inception until February 1st, 2021 was performed
according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses)
guidelines.

Results:
Thirty-one studies met our eligibility criteria and were included in the current review. In total, 435,492
patients were identified and the overall incidence of VTE was 2.19% (95% CI: 1.82-2.38). Τhe following risk
factors were associated with VTE: smoking, advanced age (>70 years), a history of diabetes mellitus, American
Society of Anesthesiologists’ (ASA) classification of Physical Health class III or IV, a history of cardiovascular
or pulmonary disease, a history of DVT or PE, elevated plasma fibrinogen level, c-reactive protein (CRP) level,
cancer stage III or IV, postoperative acute respiratory distress syndrome (ARDS), prolonged postoperative hospital
stay, previous steroid use, history of Inflammatory Bowel Disease (IBD), heart failure and neoadjuvant
and adjuvant chemotherapy.

Conclusion:
VTE remains an important complication after major abdominal surgery for cancer and seems to
increase mortality rates.
Transcription Factors and Regulators Pathway-focused Genes Expression
Analysis in Patients with Different Forms of Thyroid Pathology
Authors: Kamyshna Iryna , Kamyshnyi Aleksandr 
Published: February 2022

Background:
Autoimmune thyroiditis (AIT), a T cell-mediated organ-specific disorder,
and transcription factors have a critical role in the regulation of immune responses, especially in the
fate of T-helper cells.

Objective:
This study aims to investigate changes in the gene expression profile of transcription
factors and regulators in patients with different forms of thyroid pathology.

Methods:
We used the pathway-specific real-time PCR array (Neurotrophins and Receptors RT2
Profiler PCR Array, QIAGEN, Germany) to identify and verify transcription factors and regulators
pathway-focused genes expression in peripheral white blood cells of patients with postoperative
hypothyroidism, hypothyroidism as a result of AIT and AIT with elevated serum and antithyroglobulin
(anti-Tg) and anti-thyroid peroxidase (anti-TPO) antibodies.

Results:
It was shown that in patients with postoperative hypothyroidism FOS, NR1I2, STAT4, and
TP53 significantly increased their expression, whereas the expression of STAT1, STAT2, and
STAT3 decreased. In patients with hypothyroidism as a result of AIT, we have found increased expression
of NR1I2, STAT2, and STAT3. In contrast, the expression of STAT1 and TP53 decreased.
FOS and STAT4 mRNAs did not change their expression. In patients with AIT and elevated serum
anti-Tg and anti-TPO antibodies, the expression of FOS and NR1I2 reduced, whereas the mRNA
level of STAT3 increased. STAT1, STAT2, and STAT4 mRNAs did not change their expression.
MYC did not change its expression in all groups of patients.

Conclusions:
The results of this study demonstrate that autoimmune thyroiditis and hypothyroidism
affect the mRNA-level expression of transcription factors and regulators genes in a gene-specific
manner and that these changes to genes expression can be one of the triggers of autoimmune
inflammation progression in the thyroid gland.
Cancer Immunotherapy: An Overview of Small Molecules as Inhibitors of the Immune Checkpoint PD-1/PD-L1 (2015-2021)
Authors: Taliani Sabrina , Baglini Emma , Salerno Silvia , Barresi Elisabetta , Marzo Tiziano , Settimo Federico Da 
Published: February 2022

Abstract:
In 2018, James Allison and Tasuku Honjo received the Nobel Prize in physiology or medicine to discover tumor therapy by inhibition of negative immune regulation. Immunotherapy stimulates T-cells to fight cancer cells by blocking different immune checkpoint pathways. The interaction between programmed cell death 1 (PD-1) and its ligand PD-L1 (Programmed cell death ligand 1) is one of the main pathways. Of note, interfering with this pathway is already exploited in clinical cancer therapy, demonstrating that it is one of the key factors involved in the immune escape mechanism of cancer. The development of monoclonal antibodies (mAbs) that possess the ability to inhibit the interactions between PD-1/PD-L1 has radically made the difference in cancer immunotherapy. Yet, due to the many drawbacks of this therapy, the research shifted its efforts towards the development of novel small molecules. This may constitute hope and an arduous challenge in fighting cancer. This paper reviews the recent primary literature concerning the development of novel small molecules able to block the interaction between PD-1 and its ligand PD-L1.
Developments in the Antitumor Activity, Mechanisms of Action, Structural Modifications, and Structure-Activity Relationships of Steroidal Saponins
Authors: Huang Xuefeng , An Renfeng , Zhang Wenjin 
Published: February 2022

Abstract:
Steroidal saponins, a class of natural products formed by the combination of spirosteranes with sugars, are widely distributed in plants and have various biological activities, such as antitumor, anti-inflammatory, anti-bacterial, anti-Alzheimer's, anti-oxidation, etc. Particularly, extensive research on the antitumor property of steroidal saponins has been conducted. Steroidal sapogenins, the aglycones of steroidal saponins, also have attracted much attention due to a vast range of pharmacological activities similar to steroidal saponins. In the past few years, structural modifications on the aglycones and sugar chains of steroidal saponins have been carried out and some achievements have been made. In this mini-review, the antitumor activity, action mechanisms, and structural modifications, along with the structure-activity relationships of steroidal saponins and their derivatives, are summarized.
In vitro Delivery of HIV-1 Nef-Vpr DNA Construct Using the Human
Antimicrobial Peptide LL-37
Authors: Bolhassani Azam , Rouhollah Fatemeh , Nikyar Arash , Heshmati Masoumeh 
Published: February 2022

Background and Objectives:
DNA-based therapeutic vaccines have been proposed as a
promising strategy for the treatment of established HIV infections. However, these vaccines are often
associated with certain shortcomings, such as poor immunogenicity and low transfection efficiency. In
this study, we investigated the ability of LL-37 to deliver a potential immunogenic fusion construct
comprising HIV-1 nef and vpr genes into a mammalian cell line.

Methods:
First, the pEGFP-N1 eukaryotic expression vector harboring the HIV-1 nef-vpr fusion was
produced free of endotoxin on a large scale. Then, DNA/LL-37 complexes were prepared by coincubation
of pEGFP-nef-vpr with LL-37 for 45 minutes at different nitrogen to phosphate (N/P) ratios.
The formation of DNA/peptide complexes was investigated by gel retardation assay. Next, the stability
and morphological characteristics of the nanoparticles were evaluated. The toxicity of LL-37 and the
nanoparticles in HEK-293T cells were assessed by MTT assay. The transfection efficiency of the
DNA/LL-37 complexes was studied by fluorescence microscopy, flow cytometry, and western blot
analysis.

Results:
LL-37 formed stable complexes with pEGFP-nef-vpr (diameter of 150-200 nm) while providing
good protection against nucleolytic and proteolytic degradation. The peptide significantly affected
cell viability even at low concentrations. However, the LL-37/DNA complexes had no significant cytotoxic
effect. Treatment of cells with pEGFP-N1/LL-37 and pEGFP-nef-vpr/LL-37 resulted in transfection
of 36.32% ± 1.13 and 25.55% ± 2.07 of cells, respectively.

Conclusion:
Given these findings and the important immunomodulatory and antiviral activities of LL-
37, the use of this peptide can be further exploited in the development of novel gene delivery strategies
and vaccine design.
A Literature Review of Pulmonary Arterial Hypertension (PAH)
Authors: Panchal Ashima , Panchal Jigar , Jain Sonika , Dwivedi Jaya 
Published: February 2022

Abstract:
In 1891, German doctor E. Romberg was the first to report PAH. It is widespread throughout the world, but it is particularly problematic in India and other developing countries. Pulmonary arterial hypertension (PAH) is characterised by an increase in pulmonary arterial pres-sure as well as the emergence of progressive symptoms, such as a loss of functional ability, short-ness of breath, and fatigue.
Blood flows from the right side of the heart to the lungs through the pulmonary arteries. Pulmonary arterial pressure refers to the pressure in the arteries of the lungs (PAH). It necessitates immediate treatment because high blood pressure in the lungs causes the right side of the heart to work much harder, increasing the risk of heart failure. This article aimed to provide brief information about the prevalence, pathology, classification, and different therapies of PAH.
Fangchinoline Inhibited Proliferation of Neoplastic B-lymphoid Cells and
Alleviated Sjögren’s Syndrome-like Responses in NOD/Ltj Mice via the
Akt/mTOR Pathway
Authors: Shao Yanxiong , Yu Chuangqi , Fu Jiayao , Zhan Tianle , Ye Lei 
Published: February 2022

Backgound:
Fangchinoline is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra S. Moore that is conventionally used as an analgesic, antirheumatic, and antihypertensive drug in China. However, the application of Fanchinoline in Sjögren syndrome (SS) remains unreported.

Objective:
This study aimed to identify the potential role of Fangchinoline in the treatment of SS via altering Akt/mTOR signaling.

Methods:
First, we examined levels of p-Akt and p-mTOR in infiltrating lymphocytes of labial glands from SS patients by immunohistochemistry. Then, the effects of Fangchinoline on Raji cells and Daudi cells were investigated using the CCK-8 assay, propidium iodide (PI)/RNase, and Annexin V/PI staining. Western blotting was used to identify the levels of Akt, p-Akt(ser473), mTOR, and p-mTOR. For in vivo analyses, NOD/Ltj and wild-type ICR mice were treated with a Fangchinoline solution, an LY294002 solution (an inhibitor of the PI3K/Akt/mTOR pathway), or their solvent for 28 days. Then, salivary flow assays and hematoxylin and eosin staining of submandibular glands were performed to determine the severity of SS-like responses in the mice.

Results:
Immunohistochemical staining of labial glands from SS patients showed that activation of p-Akt and p-mTOR in infiltrating lymphocytes might be correlated with SS development. In vitro, Fangchino-line and LY294002 inhibited proliferation, induced cell cycle arrest, and promoted apoptosis in Raji and Daudi cells by altering Akt/mTOR signaling. In vivo, Fangchinoline and LY294002 significantly im-proved the salivary secretion by NOD/Ltj mice and reduced the number of lymphocytic foci in the sub-mandibular glands.

Conclusion:
These results indicated that Fangchinoline could effectively inhibit the proliferation of neo-plastic B-lymphoid cells and reduce SS-like responses in NOD/Ltj mice. Our study highlights the poten-tial value of the clinical application of Fangchinoline for SS treatment.
Highly Efficient, Reusable, Functionalized Pyridinium Salts as a Catalyst for the Simple and Cost-effective Preparation of Tetrahydro [b] Benzopyran Derivatives
Authors: Khiri-Meribout Naima , Benzerka Saida , Redouane Mohamed Abdenour , Debache Abdelmadjid 
Published: February 2022

Background:In this work, a series of pyridinium-based ionic liquids (PBILs) were synthesized.Methods:Pyridinium-based ionic liquids (PBILs) were synthesized through a simple method, which was initially evaluated as catalysts for the synthesis of tetrahydro[b]benzopyran derivatives via a one-pot three-component reaction involving aldehydes, malononitrile, and dimedone.Results:The PBILs perform well in this condensation reaction, especially 1-methylpyridin-1-ium dimethyl phosphate (MPDMP).Conclusion:The advantages of this procedure are good yields, short reaction time, simplicity of implementation, and inexpensive starting materials.
The Relation of Attitude Toward Technology and Mastery Experience After an App-Guided Physical Exercise Intervention: Randomized Crossover Trial
Authors: Sassenberg Kai , Roesel Inka , Sudeck Gorden , Bernecker Katharina , Durst Jennifer , Krauss Inga 
Published: February 2022

Background
Physical exercise has been found to assert a positive impact on many muscular conditions. Exercise under face-to-face supervision is the gold standard, but access to it is limited, for instance, for economic reasons. App-guided therapy is an intervention that is more affordable and easily accessible. However, attitude toward technology is a key predictor for media adoption and is therefore expected to shape user experience during app-guided therapy. This might be of particular importance for mastery experience, which is crucial for promoting exercise-related self-efficacy and perceived usefulness of the interaction. Both should empower patients to continuously exercise.

Objective
This study sought to test whether attitudes toward technology predict mastery experience and perceived usefulness of the interaction after an app- versus a physiotherapist-guided treatment. We expect that attitudes toward technology positively predict both outcomes in case of the app-guided but not in case of the physiotherapist-guided treatment.

Methods
Patients (n=54) with clinically diagnosed hip osteoarthritis participated in 2 training sessions with the same exercise intervention, once guided by an app on a tablet computer and once guided by a physiotherapist in a German university hospital. The order of the sessions was randomized. Attitude toward technology was assessed as predictor before the first session, while mastery experience and the global perceived usefulness of interaction as self-reported outcomes after each session.

Results
In line with our hypotheses, attitude toward technology predicted mastery experience (b=0.16, standard error=0.07, P=.02) and usefulness of interaction (b=0.17, standard error=0.06, P=.01) after the app-based training but not after the training delivered by a physiotherapist (P>.3 in all cases). Mastery experience was lower for the app-based training but reached a very similar level as the physiotherapist-guided training for those holding a very positive attitude toward technology.

Conclusions
The attitude toward technology predicts the extent of mastery experience after app-guided exercise therapy. As mastery experience is highly important for self-efficacy and future exercise behavior, attitudes toward technology should be considered when delivering app-guided exercise treatments.

Trial Registration
German Clinical Trials Register DRKS00015759; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015759