bluuebunny/crossref_metadata_2025_split huggingface dataset:
L’engagement Sociétal des Entreprises et Politique Commerciale: Cas des Entreprises Marocaines Labellisées RSE
Authors: Jihane Dinia 
Published: August 2022

La thématique de RSE occupe l’intérêt des milieux académiques depuis plusieurs années et connait un grand essor dans la pratique des entreprises. Toutefois, les recherches antérieures ont porté plus sur les fondements théoriques, l’évolution des acceptions, l’analyse des implications sociétales et organisationnelles, voire, les effets de la RSE sur la performance de l’entreprise. Alors, peu d’intérêt a été accordé aux motivations des entreprises à l’engagement sociétal, en l’occurrence, les motivations commerciales, d’où la perspective du présent travail. Il s’agit de contribuer à l’analyse de la RSE comme instrument de la politique commerciale des entreprises, à travers une étude empirique auprès des entreprises marocaines labellisées RSE de la CGEM.
Pour ce faire, nous optons pour un positionnement « positiviste aménagé » avec une démarche « hypothético-déductive », et une méthodologie d’étude quantitative. Sur le plan théorique, nous essayons d'établir un cadre d’analyse de l’approche instrumentale des motivations à l’engagement RSE. En s’appuyant sur ce développement, nous construisons nos hypothèses à vérifier qui sont testées selon l’approche PLS et traitées en utilisant le langage R. Au niveau des résultats, l’étude empirique permet de conclure que l’engagement RSE contribue bien à atteindre les objectifs de la politique commerciale de l’entreprise.
The CSR’s thematic has been of interest to the academic community for several years and is experiencing a tremendous appeal in business practice. However, previous research focused more on the theoretical foundations, the evolution of acceptances, the analysis of the societal and organizational implications, and even the effects of CSR on the company’s performance. Consequently, little attention was paid to the reasons behind the adoption of the CSR approaches, in this case, the business motives, hence the perspective of this work. The aim is to contribute to the analysis of CSR as an instrument of the company’s commercial policy through an empirical survey study of CSR labeled Moroccan companies in the General Confederation of Moroccan Companies.
To do this, we opt for a "positivist" positioning with an hypothetico-deductive method and a quantitative study methodology. On the theoretical level, we are trying to establish a framework for the theoretical analysis of the instrumental approach to the motivations for CSR engagement. Based on this development, we are building our hypotheses to be verified which are tested according to the PLS approach and processed using the R language.
At the level of results, the empirical study concludes that societal commitment contributes well to achieving the objectives of the company's commercial policy.
miR-490-3p Alleviates Cardiomyocyte Injury via Targeting FOXO1
Authors: Jiang Jin , Xu Jian , Tang Huifang 
Published: August 2022

Background:
MicroRNA-490-3p (miR-490-3p) plays a role in the pathogeneses of a
variety of cardiovascular diseases. Bioinformatic analysis showed that miR-490-3p was downregulated
in the myocardial tissues of mice with myocardial infarction (MI). Nevertheless, the
functions and mechanisms of miR-490-3p in MI remain unclear.

Methods:
This study used an in-vitro model to investigate the role of miR-490-3p in MI. Human
cardiac myocytes (HCMs) were cultured in a hypoxic environment. 3-(4,5)-Dimethylthiahiazo (-zy1)-
3,5-di-phenytetrazoliumromide (MTT) assay and flow cytometry were used to detect cell
viability and apoptosis. The expression levels of forkhead box O1 (FOXO1) and miR-490-3p were
detected by quantitative real-time PCR and Western blot. The levels of interleukin-6 (IL-6), tumor
necrosis factor-α (TNF-α), interleukin-1β (IL-1β), lactate dehydrogenase (LDH), cardiac troponin I
(cTnI), and creatine kinase MB (CK-MB) were detected by enzyme-linked immunosorbent assay
(ELISA). The targeted relationship between miR-490-3p and FOXO1 3’UTR was determined by a
dual-luciferase reporter gene assay.

Results:
miR-490-3p was significantly down-regulated in hypoxia-induced HCM cells, while
FOXO1 was markedly up-regulated. miR-490-3p overexpression inhibited HCM cell inflammatory
responses and injury after hypoxia treatment. FOXO1 was validated to be a direct target of miR-
490-3p, and its overexpression weakened the effects of miR-490-3p on cell viability, apoptosis, as
well as inflammatory responses.

Conclusion:
miR-490-3p alleviates cardiomyocyte injury via targeting FOXO1 in MI.
Phosphorylation Regulation of a Histone-like HU Protein from
Deinococcus radiodurans
Authors: Hou Jinfeng , Dai Jingli , Chen Zijing , Wang Yudong , Cao Jiajia , Hu Jing , Ye Shumai , Hua Yuejin , Zhao Ye 
Published: August 2022

Background:
Histone-like proteins are small molecular weight DNA-binding proteins
that are widely distributed in prokaryotes. These proteins have multiple functions in cellular
structures and processes, including the morphological stability of the nucleoid, DNA compactness,
DNA replication, and DNA repair. Deinococcus radiodurans, an extremophilic microorganism, has
extraordinary DNA repair capability and encodes an essential histone-like protein, DrHU.

Objective:
We aim to investigate the phosphorylation regulation role of a histone-like HU protein
from Deinococcus radiodurans.

Methods:
LC-MS/MS analysis was used to determine the phosphorylation site of endogenous
DrHU. The predicted structure of DrHU-DNA was obtained from homology modeling (Swissmodel)
using Staphylococcus aureus HU-DNA structure (PDB ID: 4QJU) as the starting model.
Two types of mutant proteins T37E and T37A were generated to explore their DNA binding
affinity. Complemented-knockout strategy was used to generate the ΔDrHU/pk-T37A and
ΔDrHU/pk-T37E strains for growth curves and phenotypical analyses.

Results and Discussion:
The phosphorylation site Thr37, which is present in most bacterial HU
proteins, is located at the putative protein-DNA interaction interface of DrHU. Compared to the
wild-type protein, one in which this threonine is replaced by glutamate to mimic a permanent state
of phosphorylation (T37E) showed enhanced double-stranded DNA binding but a weakened
protective effect against hydroxyl radical cleavage. Complementation of T37E in a DrHU-knockout
strain caused growth defects and sensitized the cells to UV radiation and oxidative stress.

Conclusions:
Phosphorylation modulates the DNA-binding capabilities of the histone-like HU
protein from D. radiodurans, which contributes to the environmental adaptation of this organism.
MicroRNA-137 Inhibits Esophageal Squamous Cell Carcinoma by Downregulating
DAAM1
Authors: Li Weina , Bai Xiangdong , Guo Ruyuan , Xing Xiaolong , Zhang Huanhu , Gao Xuezhen 
Published: August 2022

Background:
A growing body of evidence demonstrates that miR-137 acts against
cancers; however, the biological function of miR-137 in esophageal squamous cell carcinoma
(ESCC) remains to be fully understood.

Objective:
The aim of this study is to explore the role of miR-137 in ESCC.

Method:
miR-137 expression was detected by reverse-transcription quantitative polymerase chain
reaction (RT-qPCR), and target protein expression was detected by western blot. Cell counting,
colony formation and flow cytometry were employed to determine the effects of miR-137 on the
growth of ESCC cells. Dual-luciferase reporter assay was performed to validate the binding of miR-
137 with a dishevelled-associated activator of morphogenesis 1 (DAAM1) 3’-UTR.

Results:
miR-137 was shown to be down-regulated in ESCC. miR-137 expression was inversely
correlated with the 5-year survival rate of ESCC patients. Up-regulated miR-137 attenuated ESCC
proliferation and promoted ESCC cell apoptosis. Meanwhile, to further reveal how miR-137
regulated the malignant behaviors of ESCC, the downstream mRNA binding targets of miR-137
were explored. miR-137 was demonstrated to bind DAAM1 3’-UTR and repressed the expression
of DAAM1. The expression of DAAM1 and miR-137 in ESCC was inversely correlated.
Additionally, the reintroduction of DAAM1 had the capacity to reverse the negative role of miR-
137 in ESCC cell growth.

Conclusions:
These findings have uncovered the new function of miR-137 in ESCC via negatively
regulating DAAM1, suggesting miR-137 as a potent therapeutic candidate for ESCC treatment.
Advances in the Discovery of Novel Inhaled PI3Kδ Inhibitors for the
Treatment of Asthma
Authors: Wei Jun , Gu Dongyan , Yuan Leer , Sheng Rong 
Published: August 2022

Abstract:
Bronchial asthma is the most common chronic respiratory illness, the incidence
of which continues to increase annually. Currently, effective treatments for CS-resistant
asthma and severe asthma are still lacking, and new therapeutic regimens are urgently
required. PI3Kδ is a key enzyme in hematopoietic cells and represents a major target
for oncology and inflammatory disease (particularly respiratory disease, asthma and
COPD). In the case of respiratory disease, the ability to inhibit PI3Kδ in the lungs shows
a higher safety and therapeutic index relative to systemic inhibition. In recent years,
paradigm shifts have occurred in inhalation therapeutics for systemic and topical drug delivery
due to the favorable properties of lungs, including their large surface area and high
permeability. Pulmonary drug delivery possesses many advantages, including a non-invasive
route of administration, low metabolic activity, a controlled environment for systemic
absorption and the ability to avoid first bypassing metabolism. In this review, we
focus on the discovery and development of inhaled drugs targeting PI3Kδ for asthma by
focusing on their activity and selectivity, in addition to their potential in drug design
strategies using inhaled administration.
Application of Machine Learning Technology in the Prediction of ADME-
Related Pharmacokinetic Parameters
Authors: Wang Ying , Zhan Yonghua , Liu Changhu , Zhan Wenhua 
Published: August 2022

Background::
As an important determinant in drug discovery, the accurate
analysis and acquisition of pharmacokinetic parameters are very important for the clinical
application of drugs. At present, the research and development of new drugs mainly
obtain their pharmacokinetic parameters through data analysis, physiological model construction
and other methods, but the results are often quite different from the actual situation,
needing more manpower and material resources.

Objective::
We mainly discuss the application of machine learning technology in the prediction
of pharmacokinetic parameters, which are mainly related to the quantitative study
of drug absorption, distribution, metabolism and excretion in the human body, such as
bioavailability, clearance, apparent volume of distribution and so on.

Method::
This paper first introduces the pharmacokinetic parameters, the relationship between
the quantitative structure-activity relationship model and machine learning, then
discusses the application of machine learning technology in different prediction models,
and finally discusses the limitations, prospects and future development of the machine
learning model in predicting pharmacokinetic parameters.

Results::
Unlike traditional pharmacokinetic analysis, machine learning technology can
use computers and algorithms to speed up the acquisition of pharmacokinetic parameters
to varying degrees. It provides a new idea to speed up and shorten the cycle of drug development,
and has been successfully applied in drug design and development.

Conclusion::
The use of machine learning technology has great potential in predicting
pharmacokinetic parameters. It also provides more choices and opportunities for the design
and development of clinical drugs in the future.
Selective Cytotoxicity and Changes in Protein Expression of T24 Bladder
Carcinoma Permanent Cell Line after Treatment with Hemocyanins
Authors: Dolashki Aleksandar , Antonova Olga , Velkova Lyudmila , Kaynarov Dimitar , Voelter Wolfgang , Dolashka Pavlina 
Published: August 2022

Background:
Some molluscan hemocyanins (Hcs) have significant immunological and antitumor potential, enabling their application in oncology. The antitumor activity of Hcs from marine snails Rapana venosa (RvH), giant keyhole limpet Megathura crenulata (KLH) and garden snails Helix lucorum (HlH), as well as their different derivatives, were studied in vitro on a permanent T24 cell line of bladder cancer and normal urothelial cell line HL 10/29 compared to doxorubicin.

Methods:
The antiproliferative activity of the tested Hcs was determined using WST-1 assay and BrdU ELISA assay. Morphological changes in both urothelial cell lines were confirmed by fluorescence microscopy. The proteomic analysis of a cell line of bladder cancer before and after treatment with functional unit (FU) βc-HlH-h using two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and mass spectrometry revealed differences in the expression of some proteins.

Results:
Studies prove that the T24 tumor cell line is dose- and time-dependent, sensitive to the action of the tested isoforms and the glycosylated FU of these hemocyanins. Selective inhibition of T24 cell growth was observed after incubation with structural subunits (βc-HlH, RvHI and RvHII) and FUs (βc-HlH-h and RvHII-e). Fluorescent microphotographs did not show apoptotic or necrotic alterations in the normal urothelial cell line HL 10/29. The FU βc-HlH-h demonstrated the highest antiproliferative effect (similarly to doxorubicin), in which predominantly apoptotic and less late apoptotic or necrotic changes in the tumor cells were observed. Several down- and up-regulated proteins identified by proteome analysis may be associated with the apoptosis pathway.

Conclusions:
The present study illustrated the selectivity of the cytotoxic effect of Hcs against the Т24 cancer cell line. This is the first report of protein expression in T24 human bladder cancer cells under the influence of FU βc-HlH-h. That is probably due to the specific oligosaccharide structures rich in methylated hexoses exposed on the surface of βc-HlH-h.
Observation and Analysis of Clinical Efficacy of Zhuang Medicine Lotus
Acupuncture Cupping Stasis Therapy on Patients with Postherpetic
Neuralgia
Authors: Lai Jingjing , Li Meikang , Li Jie , Han Haitao , Huang Jinming , Qin Hongling , Li Xiujuan , Tan Lei , Xu Jing , Peng Jinxiu 
Published: August 2022

Objective:
To explore the clinical efficacy of Zhuang Medicine Lotus Acupuncture
Cupping Stasis Therapy on patients with postherpetic neuralgia (PHN) and its action mechanism.

Methods:
36 patients are randomly divided into Lotus Acupuncture Cupping Stasis Therapy group,
pure cupping group and gabapentin group, with a total of five observation points for the first, fifth,
tenth, fifteenth, and twentieth sessions of therapy (one session every three days). At each observation
point, the venous blood of the patients is taken, and the contents of and changes in WNT3a,
Frizzled8, β-catenin, IL-18, TNF-α, NR2B, NK-1 and SP are tested by ELISA, RT-PCR and WesternBlot,
respectively. The VAS scores and safety of the patients in the three groups are compared.

Results:
With increased time spent in therapy, the VAS scores of patients in each group decreased
gradually and there was a significant reduction in pain in patients in the Lotus Acupuncture Cupping
Stasis Therapy group compared to the gabapentin and pure cupping groups (P<0.05). The levels
of IL-18, TNF-α, NK-1, SP, WNT3a, Frizzled 8 and β-catenin in the serum of all patients experienced
a constant decline over time (P<0.05); the levels of the aforesaid factors in the serum of patients in
the Lotus Acupuncture Cupping Stasis Therapy group dropped remarkably after the tenth session of
therapy compared to those in gabapentin and pure cupping groups (P<0.05).

Conclusions:
Zhuang Medicine Lotus Acupuncture Cupping Stasis Therapy can significantly reduce
the pain of PHN patients, with a good therapeutic effect, and it is worthy of clinical use.
ASF1B, as an Independent Prognostic Biomarker, Correlates with
Immune Infiltrates in Hepatocellular Carcinoma
Authors: Li Renzhi , Cui Xiaohan , Sun Weijun , Yang Zhen , Shen Xingyuan , Zhu Chunfu 
Published: August 2022

Background:
Hepatocellular carcinoma (HCC) is one of the fastest-growing malignancies globally. The impact of surgical treatment is limited, and molecular targeted therapy has not yielded a consistent efficacy. This warrants for identification of novel molecular targets. The anti-silencing function of 1B histone chaperone (ASF1B) previously studied in numerous cancers. However, the understanding of its role in HCC is limited.

Methods:
The TIMER database used to analyze the ASF1B expression in pan-cancer and para-carcinoma tissues. ASF1B expression in HCC confirmed by using the HCCDB database, Quantitative real-time PCR (q-PCR), and Western blot (WB) assays. The relationship between clinicopathological parameters and ASF1B expression analyzed by using UALCAN, whereas the prognostic value of ASF1B was evaluated using the GEPIA database. Linkedomics and cBioportal databases used to validate the ASF1B co-expression associated with immune infiltration by the TIMER database. Moreover, cell proliferation after ASF1B-knockdown was determined through CCK8 and clone formation assays.

Results:
ASF1B was highly expressed in HCC tissues and the expression levels were linked to tumor grade, race, and disease stage. Univariate and multivariate Cox models showed that ASF1B is an independent prognostic factor in HCC. CCK8 and clone formation assays demonstrated that ASF1B promotes cell proliferation. Gene co-expression analysis in Linkedomics demonstrated that HJURP, KIF2C, KIF4A, KIF18B, and KIFC1 expression were intimately associated with ASF1B and immune infiltrate cells.

Conclusion:
This study shows that ASF1B promotes the proliferation of HCC. Besides, ASF1B could be a potential prognostic biomarker for HCC patients.
An Update On Proficiency of Voltage-gated Ion Channel Blockers in the
Treatment of Inflammation-associated Diseases
Authors: Godad Angel Pavalu , Kelkar Siddesh , Nailwal Namrata , Bhatia Nirav Yogesh , Doshi Gaurav , Sathaye Sadhana 
Published: August 2022

Abstract:
Inflammation is the body’s mechanism to trigger the immune system, thereby preventing bacteria and viruses from manifesting their toxic effect. Inflammation plays a vital role in regulating inflammatory mediator levels to initiate the wound healing process depending on the nature of the stimuli. This process occurs due to chemical release from white blood cells by elevating blood flow to the site of action, leading to redness and increased body temperature. Currently, there are numer-ous Non-steroidal anti-inflammatory drugs (NSAIDs) available, but these drugs are reported with adverse effects such as gastric bleeding, progressive kidney damage, and increased risk of heart at-tacks when prolonged use. For such instances, alternative options need to be adopted. The introduc-tion of voltage-gated ion channel blockers can be a substantial alternative to mask the side effects of these currently available drugs. Chronic inflammatory disorders such as rheumatoid and osteoarthri-tis, cancer and migraine, etc., can cause dreadful pain, which is often debilitating for the patient. The underlying mechanism for both acute and chronic inflammation involves various complex re-ceptors, different types of cells, receptors, and proteins. The working of voltage-gated sodium and calcium channels is closely linked to both inflammatory and neuropathic pain. Certain drugs such as carbamazepine and gabapentin, which are ion channel blockers, have greater pharmacotherapeutic activity for sodium and calcium channel blockers for the treatment of chronic inflammatory pain states. This review intends to provide brief information on the mechanism of action, latest clinical trials, and applications of these blockers in treating inflammatory conditions.
Diabetic Nephropathy: Pathogenesis to Cure
Authors: Gupta Jeena , Kushwaha Kriti , Kabra Uma , Dubey Rupal 
Published: August 2022

Abstract:
Diabetic nephropathy (DN) is a leading cause of end-stage renal disorder (ESRD). It is defined as the increase in urinary albumin excretion (UAE) when no other renal disease is present. DN is categorized into microalbuminuria and macroalbuminuria. Factors like high blood pressure, high blood sugar levels, genetics, oxidative stress, hemodynamic and metabolic changes affect DN. Hyperglycemia causes renal damage through activating protein kinase C (PKC), producing advanced end glycation products (AGEs) and reactive oxygen species (ROS). Growth factors, chemokines, cell adhesion molecules, inflammatory cytokines are found to be elevated in the renal tissues of the diabetic patient. Many different and new diagnostic methods and treatment options are available due to the increase in research efforts and progression in medical science. However, until now no permanent cure is available. This article aims to explore the mechanism, diagnosis, and therapeutic strategies in current use for increasing the understanding of DN
Anti-Tubercular Activity of Pyrazinamide Conjugates: Synthesis and Structure-Activity Relationship Studies
Authors: Wahan Simranpreet K. , Sharma Sangeeta , Chawla Pooja A. 
Published: August 2022

Abstract:Tuberculosis (TB) is an airborne infection caused by the bacteria Mycobacterium Tuberculosis (MTB). It mainly affects the lungs and causes severe coughing, fever, and chest pains. With the rising prevalence of drug-resistant and inactive Tuberculosis (TB), there is an essential need to discover more effective molecules capable of combating this heinous illness. Pyrazinamide is a first-line tuberculosis therapy that shortens prophylactic duration from twelve to six months. The majority of presently used tuberculosis medications were found by a mix of serendipity and innovative chemical alterations of an existing lead drug. Given that the majority of these discoveries occurred years ago, there is a definite need to use fresh methodologies and technology for discovery to meet the grave danger posed by tuberculosis and the rise of treatment resistance strains. Although current research has provided significant insight into TB transmission, diagnosis, and treatment in the last four years, much more progress is needed to successfully reduce tuberculosis prevalence and eventually eradicate it. The disease continues to be a public health concern, second only to HIV/AIDS in high fatality rates. This review focuses on current efforts to translate the antitubercular activity of all known pyrazinamide analogues and proposes a novel approach for developing new anti-tubercular drugs based on the fusion of pyrazinamide with various heterocyclic rings that shorten treatment for drug-sensitive and multidrug-resistant tuberculosis.