bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential Indicators of Mitochondrial Structure and Function
Authors: He Xu-Dong , Zhang Fan , Huang Ying , Hao Jun-Jie , Zhang Mei , He Jin-Biao , Pu Xue-Mei , Li Yan-Juan , Zi Lei , Yu Jie , Yang Xing-Xin 
Published: May 2022

Abstract:
Mitochondria regulate a range of important physiological and biochemical cellular processes including
apoptotic cell death, energy production, calcium homeostasis, oxidative stress, and lipid metabolism. Given
their role as the ‘engines’ of cells, their dysfunction is associated with a variety of disease states. Exploring the
relationship between mitochondrial function and disease can reveal the mechanism(s) of drug activity and disease
pathology. In this review, we summarized the methods of evaluating the structure and function of mitochondria,
including the morphology, membrane fluidity, membrane potential, opening of the membrane permeability
transition pore, inner membrane permeabilization, mitochondrial dynamics, mitophagy, oxidative stress,
energy metabolism-related enzymes, apoptotic pathway related proteins, calcium concentration, DNA copy
number, oxygen consumption, β-oxidation-related genes and proteins, cardiolipin content, and adenosine triphosphate
content. We believe that the information presented in this review will help explore the pathological
processes of mitochondria in the occurrence and development of diseases, as well as the activity and mechanism
of drugs, and the discovery of new drugs.
Alz-Disc: A Tool to Discriminate Disease-causing and Neutral Mutations in
Alzheimer's Disease
Authors: Gromiha M. Michael , Kulandaisamy A. , Parvathy Dharshini S. Akila 
Published: May 2022

Background:
Alzheimer's disease (AD) is the most common neurodegenerative disorder
that affects the neuronal system and leads to memory loss. Many coding gene variants are associated
with this disease and it is important to characterize their annotations.

Method:
We collected the Alzheimer's disease-causing and neutral mutations from different databases.
For each mutation, we computed the different features from protein sequence. Further, these
features were used to build a Bayes network-based machine-learning algorithm to discriminate between
the disease-causing and neutral mutations in AD.

Results:
We have constructed a comprehensive dataset of 314 Alzheimer's disease-causing and 370
neutral mutations and explored their characteristic features such as conservation scores, positionspecific
scoring matrix (PSSM) profile, and the change in hydrophobicity, different amino acid residue
substitution matrices and neighboring residue information for identifying the disease-causing
mutations. Utilizing these features, we have developed a disease-specific tool named Alz-disc, for
discriminating the disease-causing and neutral mutations using sequence information alone. The
performance of the present method showed an accuracy of 89% for independent test set, which is
13% higher than available generic methods. This method is freely available as a web server at
https://web.iitm.ac.in/bioinfo2/alzdisc/.

Conclusions:
This study is useful to annotate the effect of new variants and develop mutation specific
drug design strategies for Alzheimer’s disease.
Targeting the Pathological Hallmarks of Alzheimer’s Disease Through Nanovesicleaided Drug Delivery Approach
Authors: Roy Rubina , Bhattacharya Pallab , Borah Anupom 
Published: May 2022

Introduction:Nanovesicle technology is making a huge contribution to the progress of treatment studies for various diseases, including Alzheimer’s disease (AD). AD is the leading neurodegenerative disorder characterized by severe cognitive impairment. Despite the prevalence of several forms of anti-AD drugs, the accelerating pace of AD incidence cannot becurbed, and for rescue, nanovesicle technology has grabbed much attention.Methodology:Comprehensive literature search was carried out using relevant keywords and online database platforms. The main concepts that have been covered included a complex pathomechanism underlying increased acetylcholinesterase (AchE) activity, β-amyloid aggregation, and tau-hyperphosphorylation forming neurofibrillary tangles (NFTs) in the brain, which are amongst the major hallmarks of AD pathology. Therapeutic recommendations exist in the form of AchE inhibitors, along with anti-amyloid and anti-tau therapeutics, which are being explored at a high pace. The degree of the therapeutic outcome, however, gets restricted by the pharmacological limitations. Susceptibility to peripheral metabolism and rapid elimination, inefficiency to cross the blood-brain barrier (BBB) and reach the target brain site are the factors that lower the biostability and bioavailability of anti-AD drugs. The nanovesicle technology has emerged as a route to preserve the therapeutic efficiency of the anti-AD drugs and promote AD treatment. The review hereby aims to summarize the developments made by the nanovesicle technology in aiding the delivery of synthetic and plant-based therapeutics targeting the molecular mechanism of AD pathology.Conclusion:Nanovesicles appear to efficiently aid in target-specific delivery of anti-AD therapeutics and nullify the drawbacks posed by free drugs, besides reducing the dosage requirement and the adversities associated. In addition, the nanovesicle technology also appears to uplift the therapeutic potential of several phyto-compounds with immense anti-AD properties. Furthermore, the review also sheds light on future perspectives to mend the gaps that prevail in the nanovesicle-mediated drug delivery in AD treatment strategies.
Medicinal Plants with Anti-dengue and Immunomodulatory Activity
Authors: David Pedroza-Escobar , Irais Castillo-Maldonado , Juan-Pablo Bandt-Pulido , Mónica Salas-Rojas , Ashutosh Sharma , Daniel Nuñez-Avellaneda , Dealmy Delgadillo-Guzmán , Rubén García-Garza , Sergio-Everardo Velázquez-Gauna , Agustina Ramirez-Moreno , María-Del-Carmen Vega-Menchaca , Alejandro-David Hernández-Herrera 
Published: May 2022

Abstract:
Dengue fever is a disease with a high mortality rate around the world, which is an important issue for the health authorities of many countries. As a result of this, the search for new drugs that are effective to combat this disease has become necessary. Medicinal plants have been used since ancient times to treat a wide list of diseases, including dengue fever. In this minireview, 12 medicinal plants with known pharmacological properties are presented, which have been used in studies to evaluate their antiviral activity in vitro tests. Among the chemical agents involved in the antiviral response, found in the alcoholic extracts of these plants, are flavonoids, terpenes and alkaloids, which within the mechanism of action in blocking viral replication are considered entry inhibitors, fusion inhibitors, translation inhibitors and protease inhibitors. The present work shows whether these plants possess antiviral activity and the chemical compounds involved in this response.
Crocetin Suppresses Uterine Ischemia/Reperfusion-induced
Inflammation and Apoptosis through the Nrf-2/HO-1 Pathway
Authors: Peng Shu , Wu Yong , Wang Ying 
Published: May 2022

Background:
Uterine ischemia/reperfusion (I/R) injury often occurs during
many complex surgical procedures, such as uterus transplantation, cesarean, and
myomectomy, which may lead to the loss of uterine function and failure of the operation.
Crocetin (CRO), as one of the major active constituents from saffron extract, shows
protective effects against reactive oxygen species, inflammation, and apoptosis.
However, the role of CRO in protecting the uterus against I/R-induced injury has never
been investigated. This study aims to clarify the protective role of CRO against I/R injury
and the underlying mechanisms.

Materials and Methods:
Sprague-Dawley rats were randomly divided into five groups:
the control group, I/R group, 20 mg/kg CRO-treated I/R group, 40 mg/kg CRO-treated
I/R group, and 80 mg/kg CRO-treated I/R group. Rats were given daily gavages with
different doses of CRO or vehicle for five consecutive days. The rat uterine I/R model
was created by routine method with 1h ischemia and 3h reperfusion. The serum and
uterine tissues were collected, the changes in malondialdehyde (MDA) level and
superoxide dismutase (SOD) activity, the mRNA and protein levels of interleukin (IL)-1β,
IL-6, tumor necrosis factor (TNF)-α and IL-10, the protein levels of B-cell chronic
lymphocytic leukemia/lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), caspase-3,
nuclear factor erythroid 2-related factor (Nrf)-2, and heme oxygenase (HO)-1, were
measured. The histological changes were examined by HE staining. The number of
apoptotic cells was analyzed by flow cytometry.

Results:
Uterine I/R significantly induced MDA level, suppressed SOD activity, upregulated
levels of pro-inflammatory cytokines, down-regulated level of the antiinflammatory
cytokine, induced caspase-3-dependent apoptosis, activated the protein
expression of Nrf-2 and HO-1, and caused uterine damage. However, pre-administration
of CRO effectively reversed I/R-induced above changes and further enhanced Nrf-2/HO-
1 activation in a dose-dependent manner.

Conclusions:
Pre-administration of CRO effectively alleviates I/R-induced oxidative
stress, inflammation, apoptosis, and tissue injury probably through activating the Nrf-
2/HO-1 pathway, suggesting a protective role of CRO in I/R-induced uterus injury.
Ferroptosis Inhibitor Regulates the Disease Progression of
Systematic Lupus Erythematosus Mice Model Through Th1/Th2
Ratio
Authors: Yang Bo , Hou Shihao , Huang Shiqing , Li Hongwen , Li Yepeng 
Published: May 2022

Background:
Systematic lupus erythematosus (SLE) is an autoimmunemediated
disease. So far, there is no relevant report on ferroptosis in SLE research, and
the role of T helper 1 (Th1) and T helper 2 (Th2) cells in SLE is still unclear.

Methods:
This study employed SLE mice models with and without ferroptosis inhibitors
(Liproxstatin‑1) and normal control mice. Treated mice were analyzed with hematoxylin
and eosin (H&E) staining, immunohistochemical detection of glutathione peroxidase 4
(GPX4), malondialdehyde (MDA) detection, ELISA(enzyme-linked immunosorbent
assay) detection of Th1 and Th2 cytokines and flow cytometry detection of Th1 and Th2
ratio.

Results:
The results showed that compared with the normal group, the SLE group
exhibited significantly higher expression of anti-double-stranded deoxyribonucleic acid
(anti-dsDNA), MDA and Th1 cytokines, significantly lower expression of GPX4 and Th2
cytokines and increased Th1/Th2 ratio. Similarly, compared with the SLE group, the SLE
+ liproxstatin-1 group showed significantly low expression of anti-dsDNA, MDA and Th1
cytokines, significantly high expression of GPX4 and Th2 cytokines and reduced
Th1/Th2 ratio.

Conclusion:
These results demonstrate that ferroptosis may be involved in promoting
SLE development. Therefore, inhibiting ferroptosis may be a potential treatment for SLE.
Similarly, the Th1/Th2 ratio may have a role in promoting SLE development.
An Outlook Towards Nano-Sponges: A Unique Drug Delivery System and
its Application in Drug Delivery
Authors: Das Debasmita , Afnan Tamanna , Chhetri Pranal , Dutta Chakraborty Debarupa , Chakraborty Prithviraj 
Published: May 2022

Abstract:
Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated like gels, creams, lotions, ointments, liquid and powders etc., for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part to new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by different itineraries like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, nanosponges development procedures, numerous factors affected by nanosponge formulation, evaluation parameters, and applications in the medicinal industry.
Delocalized Lipophilic Cation Triphenyl Phosphonium: Promising Molecule
for Mitochondria Targeting
Authors: Pawar Abhishek , Korake Swati , Pawar Atmaram , Kamble Ravindra 
Published: May 2022

Abstract:
The mitochondria are a dynamic powerhouse organelle that contributes greatly to cancer
therapy. Solving the current problems that occur mostly in chemotherapy and diagnosis of various
cancers targeting the Mitochondria is an implying approach. In this review, it is discussed how the
tethering of mitochondrial-targeting moieties to chemotherapeutics, fluorescent dyes and photothermal
molecules can enhance the anticancer effect. The most extensively used mitochondrial targeting
conjugate is Triphenyl phosphonium (TPP), which is a delocalized lipophilic cation that gets easily
accumulated via the endocytosis mechanism due to the decreased mitochondrial membrane potential of
the cancer cell. Credited for this characteristic, TPP has been extensively investigated in targeting
mitochondria and delivery of cancer theranostics. This mitochondrial targeting strategy attracted great
attention in cancer targeting nanotechnology. The TPP based nanoformulation have exhibited
amplified therapeutic outcomes in the treatment of various cancer. Thus, TPP is an ultimate carrier
with magnificent potential as a mitochondrial targeting agent.
Detection of Transdermal Drug Delivery Efficiency by Shock Wave
Authors: Xie Yu-Jie , Wu Sheng-Jian , Wang Jian-Xiong , Wei-Zhang  , Sun Fu-Hua , Hu Yue , Miyamoto Akira , Xu Fang-Yuan , Zhang Chi 
Published: May 2022

Objective:
This study aimed to observe the drug distribution ex-vivo after transdermal drug
delivery (TDD) by Shock Wave (SW) and to explore the different effects of the two types of shock
waves.

Materials and Methods:
Nine female Sprague-Dawley (SD) rats were randomly divided into 3 groups:
(i) control group; (ii) RESW group (0.35mJ/mm2, 2 Hz, 400 pulse); (iii) FESW group (0.16mJ/mm2, 2
Hz, 400 pulse). Micro positron emission tomography/computed tomography (PET/CT) was used to
observe the distribution of [18]F-NaF. Furthermore, 12 SD rats were randomly divided into 4 groups:
(i) control group; (ii) FESW group 1 (0.03mJ/mm2, 2 Hz, 400 pulse); (iii) FESW group 2 (0.16mJ/mm2,
2 Hz, 400 pulse); (iv) FESW group 3 (0.35mJ/mm2, 2 Hz, 400 pulse). High-performance liquid chromatography
(HPLC) tested diclofenac sodium and glucose percutaneously TDD by FESW. Statistical
significance was conducted by analysis of variance of repeated measurement.

Results:
The micro PET/CT observed FESW could penetrate [18]F-NaF through the skin, while RESW
could not. The second study found the higher the energy of the FESW, the more diclofenac sodium and
glucose penetration. Repeated measures analysis of variance found a within-subject effect (diclofenac
sodium, F = 4.77, p = 0.03), (glucose, F = 8.95, p = 0.006), significant differences between the control
group, FESW group 1, and FESW group 2 (p < 0.05).

Conclusion:
The study found that FESW can penetrate [18]F-NaF, sugar and diclofenac sodium into the
rat body. FESW has a good indication of drug penetration, which provides new biological evidence for
route administration.
Electrospun Beads-on-the-String Nanoproducts: Preparation and Drug
Delivery Application
Authors: Chen Wei , Zhao Ping , Yang Yaoyao , Yu Deng-Guang 
Published: May 2022

Abstract:
The nanoproducts prepared by electrospinning have a large specific surface area, adjustable
porosity, and controllable structure. Therefore, electrospinning has attracted an increasing attention in
the current drug delivery systems (CDDs). In general cognition, the morphology of electrospinning
nanoproducts should be homogeneous and stable to provide reproducible functions. Thus, numerous
studies have been conducted to overcome the generation of beads-on-the-string by optimizing experimental
conditions. This review introduces a specific electrospun nanoproduct, which is beads-on-thestring
nanofibers. The presence of beads in the beads-on-the-string nanofibers can effectively encapsulate
the model drug, which reduce the initial burst release of the drug and provide sustained release. At
the same time, the beads-on-the-string nanofibers with composite structures can modulate the release
properties of model drugs in CDDs. This review mainly summarizes the current research on the preparation
of beads-on-the-string nanofibers by electrospinning and the application of beads-on-the-string
nanofibers in the field of drug delivery. The future challenges and opportunities of beads-on-the-string
nanofibers are also anticipated.
Synthesis, Structure Confirmation of Deuterium-substituted Kynurenine
and the Conformation Analysis of Kynurenine in Daptomycin
Authors: Zhang Hanzhi , Qin Feng , Sun Ning , Zheng Mengmeng , Luo Wenyan , Qiu Ya , Liu Hao , Zhang Xiangmin 
Published: May 2022

Background:
After the hydrolysis of daptomycin in deuterated hydrochloric acid, the
deuterium-substituted kynurenine was found, but the structure of deuterium-substituted kynurenine has not been reported.

Introduction:
The deuterium-substituted kynurenines were simply synthesized and confirmed
to be tri- and tetra-substituted products by high resolution mass spectrum and NMR. In further,
the deuterium-substituted kynurenines were used to determine the conformation of kynurenine
to be L-type in daptomycin through conformation analysis combined with derivation and high
performance liquid chromatography-quadrupole time-of-flight mass spectrometry (HPLCQ/TOF-MS).

Methods:
In the present study, a simple synthesis method was developed for deuteriumsubstituted kynurenine, and its structure was confirmed by high resolution mass spectrometry and
NMR. L-kynurenine was mixed with the deuterated hydrochloric acid and heated at 110 o
C for 7
h. The hydrogen/deuterium exchange products of L-kynurenine were obtained through the hydrogen/deuterium exchange method. After the derivation of deuterium-substituted L-kynurenine by
Marfey’s reagent, the conformation of kynurenine in daptomycin was deduced by HPLC-Q/TOFMS.

Results:
The deuterium-substituted kynurenines were confirmed to be tri- and tetra-substituted
products by high resolution mass spectrum. Further, Hydrogen NMR spectrum indicated that the
deuterium-substitution positions were β-position on amino acid and 3’ and 5’ positions on the
benzene ring. Thus, the tri-deuterium-substituted product was L-[β, 3’, 5’-
2
H3] kynurenine-d3,
while the tetra-deuterium-substituted product was L-[β, β, 3’, 5’-
2
H4] kynurenine-d4. Furthermore, the deuterium-substituted kynurenines were used to determine the conformation of
kynurenine to be L-type in daptomycin through conformation analysis combined with derivation
and HPLC-Q/TOF-MS.

Conclusion:
The synthesis, structures, and application of tri- or tetra- deuterium-substituted
kynurenine were reported in this study.
Optimization of Therapy in Patients with Epilepsy and Psychiatric Comorbidities: Key Points
Authors: Pisani Francesco , Rosa Pisani Laura , Barbieri Maria Antonietta , de Leon Jose , Spina Edoardo 
Published: May 2022

Abstract:Psychiatric disorder comorbidity in patients with epilepsy (PWE) is very frequent with a mean percentage prevalence of up to 50% and even higher. Such a high frequency suggests that epilepsy and psychiatric disorders might share common pathological pathways. Various aspects contribute to make the matter very complex from a therapeutic point of view. Some antiseizure medications (ASMs), namely valproic acid, carbamazepine and lamotrigine, have mood-stabilising effects and are routinely used for the treatment of bipolar disorder in patients who do not have epilepsy. Gabapentin and especially pregabalin exert anxiolytic effects. However, a number of ASMs, in particular levetiracetam, topiramate, and perampanel, may contribute to psychiatric disorders, including depression, aggressive behaviour and even psychosis. If these ASMs are prescribed, the patient should be monitored closely. A careful selection should be made also with psychotropic drugs. Although most of these can be safely used at therapeutic doses, bupropion, some tricyclic antidepressants, maprotiline, and clozapine may alter seizure threshold and facilitate epileptic seizures. Interactions between ASMs and psychotropic medication may make it difficult to predict individual response. Pharmacokinetic interactions can be assessed with drug monitoring and are consequently much better documented than pharmacodynamic interactions. Another aspect that needs a careful evaluation is patient adherence to treatment. Prevalence of non-adherence in PWE and psychiatric comorbidities is reported to reach values even higher than 70%. A careful evaluation of all these aspects contributes to optimize therapy with positive impact on seizure control, psychiatric wellbeing and quality of life.
Dietary Antioxidants and their Potential Role in Human Disease Management
Authors: Dhiman Neena K. , Saini Rashmi , Mehra Himaani , Goyal Tanisha 
Published: May 2022

Abstract:Reactive oxygen species (ROS) are usually destroyed by the antioxidant defence systems in our body. ROS in low concentrations may be beneficial or even indispensable for defence against microorganisms and in intracellular signaling, but its higher amounts can trigger negative chain reactions leading to various pathological conditions. A delicate balance between antioxidants and oxidants is maintained in healthy organisms and protection against the harmful effects of ROS is thus provided. The increase in ROS leading to oxidative stress plays a key role in the development of chronic diseases like cancer, diabetes, neurodegenerative, and cardiovascular diseases. Several non-enzymatic and enzymatic antioxidant activities exist as a safeguard against ROS accumulation. Imbalance between the oxidative stress and the antioxidant defence systems causes irreversible changes in cellular components and the normal cell signaling mechanisms are disrupted. The enzymatic and non-enzymatic antioxidant defences include catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), vitamin A, vitamin C (ascorbic acid), vitamin E (α-tocopherol), carotenes, flavonoids, etc. Several human pathologies have been known to be treated by the use of medicinal plants owing to their antioxidant properties. Dietary antioxidants such as vitamins, minerals, carotenes, and flavonoids, with their mechanisms of antioxidant defence are discussed in the review for the effective management of various human diseases.