bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Functional, Protective or Damaging Responses Associated
with Different Redox Imbalance Intensities: A Comprehensive
Review
Authors: del Campo Andrea , Valenzuela Rodrigo , Videla Luis Alberto , Zúñiga-Hernandez Jessica 
Published: December 2022

Abstract:
Reactive species (RS) are produced in aerobic and anaerobic cells at different
concentrations and exposure times, which may trigger diverse responses depending on
the cellular antioxidant potential and defensive devices. Study searches were carried out
using the PubMed database of the National Library of Medicine-National Institutes of
Health. Cellular RS include reactive oxygen (ROS), nitrogen (RNS), lipid (RLS) and
electrophilic species that determine either cell homeostasis or dysfunctional biomolecules.
The complexity of redox signalling is associated with the variety of RS produced,
the reactivity of the target biomolecules with RS, the multiplicity of the counteracting
processes available, and the exposure time. The continuous distortion in the prooxidant/
antioxidant balance favoring the former is defined as oxidative stress, whose intensity
determines (i) the basal not harmful unbalance (oxidative eustress) at RS levels in
the pM to nM range that supports physiological processes (e.g., immune function, thyroid
function, insulin action) and beneficial responses to external interventions via redox
signalling; or (ii) the excessive, toxic distortion (oxidative distress) at RS levels exceeding
those in the oxidative eustress zone, leading to the unspecific oxidation of biomolecules
and loss of their functions causing cell death with associated pathological
states. The cellular redox imbalance is a complex phenomenon whose underlying mechanisms
are beginning to be understood, although how RS initiates cell signalling is a matter
of debate. Knowledge of this aspect will provide a better understanding of how RS
triggers the pathogenesis and progression of the disease and uncover future therapeutic
measures.
Identification of the Key Active Pharmaceutical Ingredients of Yishen
Qutong Granule, A Chinese Medicine Formula, In The Treatment of Primary
Lung Cancer
Authors: Chen Jiayang , Feng Li , Jin Wei , Chang Jinyuan , Li Jie , Li Hao 
Published: December 2022

Background:
Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Traditional Chinese medicine (TCM) reportedly has potential therapeutic effects against LC.

Objective:
This study aimed to investigate the antitumor efficacy of Yishen Qutong granule (YSQTG) in primary LC treatment, to identify its key active pharmaceutical ingredients (APIs), and to explore its possible mechanism of action.

Methods:
The antitumor role of YSQTG was validated via cell function assays and a xenograft tumor model. Then, high-performance liquid chromatography-mass spectrometry (HPLC–MS) was performed to determine the objective precipitation components of YSQTG, followed by target prediction through reference to databases. Subsequently, the proportion of the predicted targets that underwent actual changes was identified via RNA-sequencing. Enrichment analysis was performed to explore the possible mechanisms of action. Hub genes were screened, and western blotting was used to verify their protein expression levels to identify the core target. Molecular docking between the active compounds and the verified core target was performed, combined with an evaluation of the potential efficacy of candidate compounds using meta-analysis to screen the candidate key APIs.

Results:
Experiments confirmed that YSQTG could inhibit LC cell proliferation, induce apoptosis in vitro, and inhibit lung tumor growth in vivo. HPLC-MS, RNA-seq, and enrichment analysis showed that oxidative stress-related pathways were the possible mechanism of YSQTG in primary LC treatment. Western blot verification indicated that heme oxygenase 1 (HMOX1, HO-1) could be the core target. Molecular docking and meta-analysis suggested that genistein and quercetin were the candidate key APIs.

Conclusion:
YSQTG and its active ingredients, genistein and quercetin, may have therapeutic effects against LC through their action on the downregulation of oxidative stress-related HMOX1 protein expression.
Influence of Zhuanggu Guanjie Pill on Seven Cytochrome P450 Enzymes Based on
Probe Cocktail and Pharmacokinetics Approaches
Authors: Chai Yuan-Yuan , Xu Yun-Xia , Xia Zi-Yin , Li An-Qin , Huang Xin , Zhang Lu-Yong , Jiang Zhen-Zhou 
Published: December 2022

Background:
The use of herbal medicines has tremendously increased over the past few decades. Case
reports and controlled clinical investigations of herbal-drug interactions have been reported. Since Cytochrome P450
(CYP) enzymes play an important role in drug interactions. The evaluation of the influence of herbal medicines on
the activities of CYPs is beneficial to promote scientific and rational clinical use of herbal medicines.

Objective:
Herein, we aimed to develop and validate a method to simultaneously quantify seven CYP cocktail probe
drugs consisting of phenacetin (PNC), bupropion (BPP), losartan potassium (LK), omeprazole (OMP), dextromethorphan
(DM), chlorzoxazone (CZZ) and midazolam (MDZ) and their respective metabolites in a single acquisition
run and use this method to evaluate the influence of Zhuanggu Guanjie Pill (ZGGJP) on seven CYPs.

Methods:
A cost-effective and simple UHPLC-(±)ESI-MS/MS method for simultaneous determination of seven
probe drugs and metabolites in rat plasma was developed and validated. Male and female rats were randomly divided
into three groups and treated with 1.2 g/kg/d ZGGJP, 5 g/kg/d ZGGJP and 0.5% CMC-Na for 14 consecutive days.
After 24 h of the last administration, all rats were administrated orally with probe drugs. The influence of ZGGJP on
the CYPs was carried out by comparing the metabolic ratio (Cmax, AUC0-t) of metabolites/probe drugs in rats.

Results:
The calibration curves were linear, with correlation coefficient > 0.99 for seven probe drugs and their corresponding
metabolites. Intra- and inter-day precisions were not greater than 15% RSD and the accuracies were within
±15% of nominal concentrations. The ZGGJP showed significant inductive effect on CYP1A2, CYP2B6, CYP2C9
and CYP3A in male and female rats.

Conclusion:
ZGGJP had inductive effects on CYP1A2, CYP2B6, CYP2C9 and CYP3A in male and female rats.
Acid-sensing Ion Channels: Implications for Intervertebral Disc
Degeneration
Authors: Zhang Hai-hong , Ran Rui , Wu Yi 
Published: December 2022

Abstract:
Intervertebral disc degeneration (IDD) is the leading cause of lower back pain and seriously
affects the quality of life of patients. The intervertebral disc (IVD) is an environment of hypoxia,
ischemia, acidity, and hypertonicity. Matrix acidity potentially negatively affects gene expression,
activity, proliferation, and apoptosis of IVD cells. Acid-sensing ion channels (ASICs) are
a group of proton-gated ion channels that play important roles in physiological and pathological
conditions. The distribution of ASICs in the nucleus pulposus (NP), annulus fibrosus, cartilage endplate,
and nucleus pulposus mesenchymal stem cells (NP-MSCs), as well as the special functions of
ASIC1a and ASIC3, show that ASICs play an important role in IDD. In this review, we comprehensively
discuss the roles of ASICs in the development and basic pathology of IDD and their potential
relevance as therapeutic targets. A deeper understanding of the roles of ASICs in these processes
may provide novel therapeutic targets for IDD prevention and treatment.
Epigenetic Regulator ASXL2: Structure, Function and its Predictive Value
in Diseases
Authors: Dong Chunming , Li Mengru , Xu Lijun , Zhang Rui 
Published: December 2022

Abstract:
ASXL2, as a transcription regulator, is a research hotspot for tumor detection. The aberrant expression of ASXL2 protein has been mainly implicated in malignant hematological and heart diseases. To further explore the predictive value of ASXL2 in diseases, we reviewed the structure and function of ASXL2 protein, the post-translational modification mechanism, and the expression of ASXL2 protein in the pathogenesis of different diseases to provide a theoretical basis and support for the development of future treatments.
The Roles of IGF-1 and MGF on Nerve Regeneration under Hypoxia-
Ischemia, Inflammation, Oxidative Stress, and Physical Trauma
Authors: Sha Yongqiang , Wang Chunli , Chen Liping , Xu Chunming , Zhang Beibei , Hong Huhai 
Published: December 2022

Abstract:
Nerve injuries and lesions often lead to the loss of neural control, reducing the patients’ quality of life. Nerve self-repair is difficult due to the low regeneration capacity, insufficient secretion of neurotrophic factors, secondary complications, and adverse microenvironmental conditions such as severe hypoxia-ischemia, inflammation, and oxidative stress. Effective therapies that can accelerate nerve regeneration have been explored. Cytokine therapy can significantly improve neural survival and myelin regeneration during nerve repair. Insulin-like growth factor-1 (IGF-1) and its isoforms (IGF-1Ea and IGF-1Eb/Ec [also known as MGF]) represent a promising therapeutic approach regarding nerve repair, given their well-described proliferative and anti-apoptotic capacities on neurons withstanding the adverse environmental conditions. This review summarizes the research progress regarding the effects of IGF-1 and its isoforms on nerve repair after nerve injury, hypoxic-ischemic insult, inflammation, and oxidative stress. We provide a theoretical basis for the clinical treatment of nerve injuries.
Superoxide Dismutase Inhibitors against Malaria, Leishmaniasis, and
Chagas Disease: Systematic Review
Authors: dos Santos Junior Manoelito Coelho , Carneiro Araújo Janay Stefany , de Mattos Oliveira Larissa , de Andrade Kaio Vinícius Freitas , Guimarães Benevides Raquel , Andrade Leite Franco Henrique 
Published: December 2022

Introduction:
Diseases caused by protozoa are one of the leading causes of death world-wide, especially in tropical regions such as Brazil. Chagas disease, leishmaniasis, and malaria are responsible for around 234 million cases and more than 400,000 deaths worldwide. Despite this scenario, drugs for these diseases have several limitations, which justifies the search for new treat-ments. Iron superoxide dismutase is a promising target for the drug design to treat patients with these diseases. It is a validated target and protects against oxidative stress.

Aim:
Thus, this systematic review aimed to synthesize evidence on the importance of superoxide dismutase in the drug design to treat patients with this protozoosis.

Method:
A search was performed for in vitro and in vivo studies, without publication and language restrictions, in MEDLINE (PubMed), LILACS (BVS), Science Direct, and EMBASE (Elsevier). Studies that pointed to the relationship between the reduction or increase in superoxide dismutase activity and the diseases were included. 23 studies were selected for the qualitative synthesis.

Result:
The results showed that the inhibition or reduction of the enzyme activity decreases the de-gree of infection and reinfection and improves the results in treating these diseases. In contrast, the increase in activity caused a high degree of survival and resistance of the parasites.

Conclusion:
However, the overall quality of evidence is low and more studies with methodological rigor are provided.
US-FDA Approved Drugs in 2020 and 2021: A Review
Authors: Passi Indu , Salwan Sushant , Kumar Bhupinder 
Published: December 2022

Introduction:
Throughout the years, the disruption caused by COVID-19 continues to pose
an excess of challenges for the pharmaceutical industry. Throughout the entire year, questions were
raised that does COVID-19 have a negative impact on new drug approvals. However, the answer to
those questions was a ‘big no’.

Methods:
We propose a compilation and analysis of around 100 medications, including small new
molecular entities (NMEs), approved by the US Food and Drug Administration for the years 2020 and
2021. Novel drug discovery is crucial for pharmaceutical research and development as well as patient
care. The only possible way to achieve this crucial goal is to repurpose current medications that may
have anticipated effects as possible candidates. The availability of new drugs and biological products
often means new treatment options for patients and advances in health care

Results:
Around 40% of the drugs were approved for various types of cancers. Other major therapeutic
areas that were focused on were neurological products (around 17%), infectious diseases (13-15%),
and cardiovascular disorders (7-8%). Various new products were approved for rare diseases (58-60%).
This study aimed to discover a pattern in FDA medicine approvals during the last two decades.

Conclusion:
This data shows that anticancer medicines and biologics are receiving increased attention
in research. With a bigger number of biologically derived medications being produced, the price could
rise much higher. FDA should embrace innovative techniques that will stimulate the industry to enhance
research and development of novel compounds or medications that can deliver considerable
improvements over existing ones. To put it briefly, FDA had to update our approach to regulation as a
whole in order to effectively develop the types of technologies that are becoming available. Modernizing
medical product review programmes is a part of this. These initiatives are part of the Medical Innovation
Access Plan.
Geiparvarin Inhibits the Progression of Osteosarcoma by Down-regulating
COX2 Expression
Authors: Chen Shu , Zou Hua , Wang Bin , Du Jia , Zhang Zhiming , Huang Ping 
Published: December 2022

Background:
Geiparvarin (GN) is a natural compound isolated from the leaves of Geijera parviflora and exhibits anticancer activity. Nevertheless, little is known about its anticancer mechanism and anti-osteosarcoma (OS) effects.

Aim:
This study explored whether GN effectively inhibits the growth and metastasis of osteosarcoma (OS) through a series of in vitro and in vivo experiments.

Methods:
Cell proliferation was measured by colony formation and MTT assays, and cell invasion was detected by Transwell assay. Flow cytometry and caspase-3 activity assays were carried out to examine cell apoptosis, and western blot analysis was performed to assess protein expression. In the animal experiments, the changes in relevant indexes were determined by immunohistochemistry and tumor vessel imaging.

Results:
Animal experiments showed that GN treatment significantly inhibited the growth and lung metastasis of OS, accompanied by increased apoptosis. In addition, GN treatment notably diminished COX2 expression and angiogenesis in OS. Moreover, COX2 overexpression nullified GN-induced decline in angiogenesis, growth, and lung metastasis and increased apoptosis in OS. Of note, the body weight of mice was enhanced after GN treatment, and the pathological examination manifested that GN treatment did not cause any damage to major organs.

Conclusion:
Our data indicated that GN might depress the growth, metastasis, and angiogenesis of OS by decreasing COX2 expression, suggesting GN is a favorable candidate drug for OS treatment without side effects. Hence, it can be concluded that geiparvarin inhibits OS progression by reducing COX2 expression.
Review on the Developments of Benzothiazole-containing Antimicrobial Agents
Authors: Haroun Michelyne 
Published: December 2022

Abstract:The infectious diseases caused by bacterial resistance to antibiotics constitute an increasing threat to human health on a global scale. An increasing number of infections, including tuberculosis, pneumonia, salmonellosis and gonorrhea, are becoming progressively challenging to cure owing to the ineffectiveness of current clinically used antibiotics and presents a serious health threat worldwide in medical community. The major concern of this global health threat is the ability of microorganisms to develop one or several mechanisms of resistance to antibiotics, making them inefficient to therapeutic treatment. The quest for discovering novel scaffold with antimicrobial property is particularly in great need to face future challenges in hospital and healthcare settings. Hence, the development of benzothiazoles is of considerable interest to medicinal chemists. Benzothiazole, being part of an important class of heterocyclic scaffold retains a wide spectrum of various attractive pharmacological activities. Antibiotic resistance represents an increasing burden comprising medical cost, hospital stay and mortality. Several derivatives containing a benzothiazole scaffold, reported in the literature, were found to display remarkable potencies towards diverse Gram-positive and Gram-negative bacterial pathogens. The principal focus concerns the antibacterial potential of benzothiazole-based derivatives as antimicrobial agents interacting with targets in bacterial pathogens. In this review, we also disclose the significance of the benzothiazole moiety in the discovery of new antibacterial compounds, the potential of benzothiazole-based derivatives in the case of resistant bacterial strains, optimization of their antibacterial activity, and their future perspectives. The structure-activity relationship study and the mode of action of the title derivatives are highlighted too.
Enhancing Psychological Interventions for Post-Traumatic Stress Disorder
(PTSD) Treatment with Memory Influencing Drugs
Authors: Marchetta Enrico , Mancini Giulia F. , Morena Maria , Campolongo Patrizia 
Published: December 2022

Abstract:
Post-traumatic stress disorder (PTSD) is a chronic psychiatric disease resulting from the
experience or witnessing of traumatic events. Persistent PTSD symptoms impair patients’ daily quality
of life, jeopardizing sleep, mood, sociability, and arousal. Recommended psychological or pharmacological
interventions are effective only in a small portion of patients and often lead to relapse. Thus,
there is a critical need to address a lack of advancement in the treatment of PTSD. The combination of
psychological interventions, aimed at facilitating the extinction of the traumatic memory, and pharmacological
medications, represents a promising tool for PTSD treatment. Timely use of psychotherapy
in conjunction with pharmacological treatments, rather than monotherapy, could thus determine a synergistic
effect by potentiating the effects of psychological interventions. In such a scenario, drugs that
modulate cognitive processes involved in the development and/or persistence of post-traumatic symptomatology
could be of great help to improve the outcome of psychotherapies and patients' prognosis.
The purpose of the present article is to review the current data available from clinical trials on combined
pharmacological treatments with psychological interventions in PTSD therapy. An overview of
findings from animal studies that prompted clinical research is also discussed.
Role of Microglia in Psychostimulant Addiction
Authors: da Silva Maria Carolina Machado , Iglesias Lia Parada , Candelario-Jalil Eduardo , Khoshbouei Habibeh , Moreira Fabrício Araujo , de Oliveira Antônio Carlos Pinheiro 
Published: December 2022

Abstract:
The use of psychostimulant drugs can modify brain function by inducing changes in the reward
system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic
pathway. However, the etiopathogenesis of addiction is a much more complex process.
Previous data have suggested that microglia and other immune cells are involved in events associated
with neuroplasticity and memory, which are phenomena that also occur in addiction. Nevertheless,
how dependent is the development of addiction on the activity of these cells? Although the mechanisms
are not known, some pathways may be involved. Recent data have shown psychoactive substances
may act directly on immune cells, alter their functions and induce various inflammatory mediators
that modulate synaptic activity. These could, in turn, be involved in the pathological alterations
that occur in substance use disorder. Here, we extensively review the studies demonstrating how cocaine
and amphetamines modulate microglial number, morphology, and function. We also describe the
effect of these substances in the production of inflammatory mediators and a possible involvement of
some molecular signaling pathways, such as the toll-like receptor 4. Although the literature in this
field is scarce, this review compiles the knowledge on the neuroimmune axis that is involved in the
pathogenesis of addiction, and suggests some pharmacological targets for the development of pharmacotherapy.
Virtual Screening of Telaprevir and Danoprevir Derivatives for Hepatitis C Virus NS3/4A Protease Inhibitors
Authors: Sarkar Kaushik , Das Rajesh Kumar 
Published: December 2022

Background:
The NS3/4A protease is a common target for inhibiting hepatitis C virus (HCV)
infection. Telaprevir and danoprevir have promising activity in combating these virus-associated infections
and are used as HCV protease inhibitors.

Objective:
In this study, we have found different tested derivative compounds for developing various
HCV NS3/4A protease inhibitors by designing the chemical structures of telaprevir and danoprevir.

Methods:
In silico studies were carried out to find better drug candidatures from these derivative compounds.
The docking studies were performed on HCV NS3/4A protease receptors (PDB: 3SV6 & 5EQR)
using Autodock vina. DFT, global reactivity, ADME (Absorption, distribution, metabolism & excretion),
and toxicity analysis were also performed for these designed compounds. The stability of the proteinligand
complexes was quantified by MD simulation and MMPBSA studies.

Results:
16 derivatives (four as telaprevir and twelve as danoprevir) have satisfied higher binding affinity
of interaction with NS3/4A protease, compared to telaprevir and danoprevir. These compounds have also
passed all rules of drug candidature to serve as the best HCV inhibitors.

Conclusion:
These 16 ligands can be effective inhibitors against HCV NS3/4A protease. These ligands
must obey the drug candidate behavior by in vitro and in vivo analysis to inhibit HCV infection.
Comparative QSAR Modeling for Predicting Anticancer Potency of
Imidazo[4,5-b]Pyridine Derivatives Using GA-MLR and BP-ANN Techniques
Authors: Jafari Mahdi , Isfahani Tahereh Momeni , Shafiei Fatemeh , Senejani Masumeh Abdoli , Alimoradi Mohammad 
Published: December 2022

Background:
Prediction of toxicity of imidazo[4,5-b]pyridine derivatives is carried out using
GA-MLR and BPANN methods.

Objective:
A quantitative structure-property relationship (QSPR) was determined based on methods, including
genetic algorithm-multiple linear regression (GA-MLR) and backpropagation artificial neural
network (BP-ANN). These methods were employed for modeling and predicting the anticancer potency
of imidazo[4,5-b]pyridine derivatives.

Materials and Methods:
A dataset of imidazo[4,5-b]pyridine derivatives was randomly divided into two
groups, training and test sets consisting of 75% and 25% of data points, respectively. The optimized conformation
of compounds was obtained using the DFT-B3LYP method and 6-31G* basis sets level with
Gaussian 09 software. A large number of molecular descriptors were calculated using Dragon software.
The QSAR models were optimized using multiple linear regressions (MLR).

Results:
The most relevant molecular descriptors were obtained using the genetic algorithm (GA) and
backward stepwise regression. The predictive powers of the GA-MLR models were studied using leaveone-
out (LOO) cross-validation and an external test set.

Conclusion:
The obtained results of statistical parameters showed the BP-ANN model to have better
performance compared to the GA-MLR model.
To assess the predictive ability of QSAR models, many statistical terms, such as correlation coefficient
(R2), leave-one-out cross-validation (LOOCV), root mean squared error (RMSE), and external and internal
validation were used. The results of validation methods demonstrate the QSAR model to be robust
and with high predictivity.