bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of Domain Segmentation of B19V VP1u Using Intein
Technology for Structural Studies
Authors: Lakshmanan Renuk Varayil , Agbandje-McKenna Mavis , McKenna Robert 
Published: January 2024

Introduction:
Parvovirus B19 (B19V) is a human pathogen, and the minor capsid protein of B19V possesses a unique N terminus called VP1u that plays a crucial role in the life cycle
of the virus

Objective:
The objective of this study was to develop a method for domain segmentation of B19
VP1u using intein technology, particularly its receptor binding domain (RBD) and phospholipase
A2 (PLA2
) domain.

Methods:
RBD and PLA2
domains of VP1u were each fused to the DnaE split inteins derived
from the Nostoc punctiforme. Each of these precursor proteins was expressed in E. coli. Combining the purified precursors in equal molar ratios resulted in the formation of full-length VP1u. Furthermore, Circular Dichroism (CD) spectroscopy and PLA2
assays were used to probe the structure and activity of the newly formed protein.

Results:
The CD spectrum of the full length VP1u confirmed the secondary structure of protein,
while the PLA2
assay indicated minimal disruption in enzymatic activity.

Conclusion:
This method would allow for the selective incorporation of NMR-active isotopes into either of the VP1u domains, which can reduce signal overlap in NMR structural determination
studies.
The Potential of Epigallocatechin Gallate in Targeting Cancer Stem
Cells: A Comprehensive Review
Authors: Chaudhuri Rupa , Samanta Anurima , Saha Priyanka , Ghosh Sukanya , Sinha Dona 
Published: January 2024

:
The dreadful scenario of cancer prevails due to the presence of cancer stem
cells (CSCs), which contribute to tumor growth, metastasis, invasion, resistance to chemo-
and radiotherapy, and recurrence. CSCs are a small subpopulation of cells within
the tumor that are characterized by self-renewal capability and have the potential to manifest
heterogeneous lineages of cancer cells that constitute the tumor. The major bioactive
green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been fruitful in downgrading
cancer stemness signaling and CSC biomarkers in cancer progression. EGCG
has been evidenced to maneuver extrinsic and intrinsic apoptotic pathways in order to decrease
the viability of CSCs. Cancer stemness is intricately related to epithelial-mesenchymal
transition (EMT), metastasis and therapy resistance, and EGCG has been evidenced
to regress all these CSC-related effects. By inhibiting CSC characteristics EGCG
has also been evidenced to sensitize the tumor cells to radiotherapy and chemotherapy.
However, the use of EGCG in in vitro and in vivo cancer models raises concern about its
bioavailability, stability and efficacy against spheroids raised from parental cells. Therefore,
novel nano formulations of EGCG and adjuvant therapy of EGCG with other phytochemicals
or drugs or small molecules may have a better prospect in targeting CSCs.
However, extensive clinical research is still awaited to elucidate a full proof impact of
EGCG in cancer therapy.
The Significance and Importance of dPCR, qPCR, and SYBR Green PCR Kit
in the Detection of Numerous Diseases
Authors: Shahrajabian Mohamad Hesam , Sun Wenli 
Published: January 2024

Abstract:
Digital PCR (dPCR) is the latest technique that has become commercially accessible for various
types of research. This method uses Taq polymerase in a standard polymerase chain reaction (PCR) to amplify
a target DNA fragment from a complex sample, like quantitative PCR (qPCR) and droplet digital PCR (dd-
PCR). ddPCR may facilitate microRNA (miRNA) measurement, particularly in liquid biopsy, because it has
been proven to be more effective and sensitive, and in this method, ddPCR can provide an unprecedented
chance for deoxyribonucleic acid (DNA) methylation research because of its capability to increase sensitivity
and precision over conventional PCR-based methods. qPCR has also been found to be a valuable standard technique
to measure both copy DNA (cDNA) and genomic DNA (gDNA) levels, although the finding data can be
significantly variable and non-reproducible without relevant validation and verification of both primers and
samples. The SYBR green quantitative real-time PCR (qPCR) method has been reported as an appropriate
technique for quantitative detection and species discrimination, and has been applied profitably in different experiments
to determine, quantify, and discriminate species. Although both TaqMan qRT-PCR and SYBR
green qRT-PCR are sensitive and rapid, the SYBR green qRT-PCR assay is easy and the TaqMan qRT-PCR
assay is specific but expensive due to the probe required. This review aimed to introduce dPCR, qPCR, SYBR
green PCR kit, and digital PCR, compare them, and also introduce their advantages in the detection of different
diseases.
Free Radicals, Mitochondrial Dysfunction and Sepsis-induced Organ
Dysfunction: A Mechanistic Insight
Authors: Kumar Sanni , Srivastava Vijay Kumar , Kaushik Sanket , Saxena Juhi , Jyoti Anupam 
Published: January 2024

Abstract:
Sepsis is a complex clinical condition and a leading cause of death worldwide. During Sepsis, there
is a derailment in the host response to infection, which can progress to severe sepsis and multiple organ dysfunction
or failure, which leads to death. Free radicals, including reactive oxygen species (ROS) generated predominantly
in mitochondria, are one of the key players in impairing normal organ function in sepsis. ROS contributing
to oxidative stress has been reported to be the main culprit in the injury of the lung, heart, liver, kidney,
gastrointestinal, and other organs. Here in the present review, we describe the generation, and essential
properties of various types of ROS, their effect on macromolecules, and their role in mitochondrial dysfunction.
Furthermore, the mechanism involved in the ROS-mediated pathogenesis of sepsis-induced organ dysfunction
has also been discussed.
Harnessing the Pyrazine Moiety for Potent Anti-inflammatory Activity: A
Comprehensive Review
Authors: Singh Kuldeep , Gupta Jeetendra Kumar , Shah Kamal , Saha Sunam , Babu Marianesan Arockia , Kumar Shivendra , Agrawal Mohit 
Published: January 2024

Abstract:
Inflammation is an intricate physiological reaction that has a vital function in the
body's protection against detrimental stimuli. Nevertheless, uncontrolled inflammation may
result in the development of long-term conditions, such as arthritis, cardiovascular disorders,
and even cancer. Scientists are always searching for new medicinal substances that
might efficiently regulate the inflammatory response. Due to its distinctive structure and an
extensive array of chemical interactions, the pyrazine moiety has emerged as a viable foundational
component for synthesising anti-inflammatory drugs. This review article examines
the many methods used to use the potential of pyrazine moiety for its anti-inflammatory
capabilities. The paper focuses on the latest progress in the development, creation, and assessment
of pyrazine-based compounds, demonstrating their modes of action and links between
their structure and activity. This review aims to provide a complete overview of the current knowledge on
pyrazine-derived compounds with anti-inflammatory action by gathering and critically analysing the latest research
results. Moreover, the essay explores the difficulties and possibilities in this area, which sets the stage for
the logical development of advanced anti-inflammatory substances using the pyrazine pattern.
An In Silico Approach to Exploring the Antinociceptive Biological
Activities of Linalool and its Metabolites
Authors: da Silva Pablo Rayff , Nunes Pazos Natalia Diniz , de Andrade Jéssica Cabral , de Sousa Natália Ferreira , Oliveira Pires Hugo Fernandes , de Figueiredo Lima Jaislânia Lucena , Dias Arthur Lins , da Silva Stiebbe Salvadori Mirian Graciela , de Oliveira Golzio Adriana Maria Fernandes , de Castro Ricardo Dias , Scotti Marcus T. , Patil Vaishali M. , Bezerra Felipe Cícero Francisco , de Almeida Reinaldo Nóbrega , Scotti Luciana 
Published: January 2024

Abstract:
Pain is characterized by the unpleasant sensory and emotional sensation associated with
actual or potential tissue damage, whereas nociception refers to the mechanism by which noxious
stimuli are transmitted from the periphery to the CNS. The main drugs used to treat pain are nonsteroidal
anti-inflammatory drugs (NSAIDs) and opioid analgesics, which have side effects that limit
their use. Therefore, in the search for new drugs with potential antinociceptive effects, essential
oils have been studied, whose constituents (monoterpenes) are emerging as a new therapeutic possibility.
Among them, linalool and its metabolites stand out. The present study aims to investigate the
antinociceptive potential of linalool and its metabolites through a screening using an in silico approach.
Molecular docking was used to evaluate possible interactions with important targets involved
in antinociceptive activity, such as α2-adrenergic, GABAergic, muscarinic, opioid, adenosinergic,
transient potential, and glutamatergic receptors. The compounds in the investigated series obtained
negative energies for all enzymes, representing satisfactory interactions with the targets and
highlighting the multi-target potential of the L4 metabolite. Linalool and its metabolites have a high
likelihood of modulatory activity against the targets involved in nociception and are potential candidates
for future drugs.
Implication of Thioredoxin 1 and Glutaredoxin 1 in H2O2-induced Phosphorylation of JNK and p38 MAP Kinases
Authors: Poulios Efthymios , Roupaka Vasiliki , Giaginis Constantinos , Galaris Dimitrios , Spyrou Giannis 
Published: January 2024

Background:
Aerobic organisms continuously generate small amounts of
Reactive Oxygen Species (ROS), which are involved in the oxidation of sensitive
cysteine residues in proteins, leading to the formation of disulfide bonds. Thioredoxin
(Trx1) and Glutaredoxin (Grx1) represent key antioxidant enzymes reducing disulfide
bonds.

Objective:
In this work, we have focused on the possible protective effect of Trx1 and
Grx1 against oxidative stress-induced DNA damage and apoptosis-signaling, by
studying the phosphorylation of MAP kinases.

Methods:
Trx1 and Grx1 were overexpressed or silenced in cultured H1299 non-small
cell lung cancer epithelial cells. We examined cell growth, DNA damage, and the
phosphorylation status of MAP kinases following treatment with H2O2.

Results:
Overexpression of both Trx1 and Grx1 had a significant impact on the growth
of H1299 cells and provided protection against H2O2-induced toxicity, as well as acute
DNA single-strand breaks. Conversely, silencing of these proteins exacerbated DNA
damage. Furthermore, overexpression of Trx1 and Grx1 inhibited the rapid
phosphorylation of JNK (especially at 360 min of treatment, ****p=0.004 and
**p=0.0033 respectively) and p38 MAP kinases (especially at 360 min of treatment,
****p<0.0001 and ***p=0.0008 respectively) during H2O2 exposure, while their silencing
had the opposite effect (especially at 360 min of treatment, ****p<0.0001).

Conclusion:
These results suggest that both Trx1 and Grx1 have protective roles
against H2O2 induced toxicity, emphasizing their significance in mitigating oxidative
stress-related cellular damage.
Transdermal Drug Delivery System of Linagliptin Sustained-release Microparticle Gels: In vitro Characterization and In vivo Evaluation
Authors: Liu Jiayan , Guo Song , Hong Shuai , Piao Jingshu , Piao Mingguan 
Published: January 2024

Background:
Linagliptin (LNG) exhibits poor bioavailability and numerous side effects,
significantly limiting its use. Transdermal drug delivery systems (TDDS) offer a potential solution to
overcome the first-pass effect and gastrointestinal reactions associated with oral formulations.

Objective:
The aim of this study was to develop LNG microparticle gels to enhance drug bioavailability
and mitigate side effects.

Methods:
Linagliptin hyaluronic acid (LNG-HA) microparticles were prepared by spray drying
method and their formulation was optimized via a one-factor method. The solubility and release were
investigated using the slurry method. LNG-HA microparticle gels were prepared and optimised using
in vitro transdermal permeation assay. The hypoglycaemic effect of the LNG-HA microparticle gel
was examined on diabetic mice.

Results:
The results indicated that the LNG-HA microparticle encapsulation rate was 84.46%. Carbomer
was selected as the gel matrix for the microparticle gels. Compared to the oral API, the microparticle
gel formulation demonstrated a distinct biphasic release pattern. In the first 30 minutes,
only 43.56% of the drug was released, followed by a gradual release. This indicates that the formulation
achieved a slow-release effect from a dual reservoir system. Furthermore, pharmacodynamic
studies revealed a sustained hypoglycemic effect lasting for 48 hours with the LNG microparticle gel
formulation.

Conclusion:
These findings signify that the LNG microparticle gel holds significant clinical value
for providing sustained release and justifies its practical application.
The Neurobiology of Formal Thought Disorder
Authors: Dornelles Erik , Correia Diogo Telles 
Published: January 2024

:
The concept of Formal Thought Disorder (FTD) is an ambiguous and disputed one,
even though it has endured as a core psychopathological construct in clinical Psychiatry. FTD can
be summarized as a multidimensional construct, reflecting difficulties or idiosyncrasies in thinking,
language, and communication in general and is usually subdivided into positive versus negative.
In this article, we aim to explore the putative neurobiology of FTD, ranging from changes in
neurotransmitter systems to alterations in the functional anatomy of the brain. We also discuss recent
critiques of the operationalist view of FTD and how they might fit in its biological underpinnings.
We conclude that FTD might be the observable phenotype of many distinct underlying alterations
in different proportions.
Density Functional Theory Study of Interaction between Ibuprofen and
Alginic Acid for Targeted Drug Delivery
Authors: Shahi Masoumeh , Falahati Donya , Ashtari Fatemeh 
Published: January 2024

Abstract:
The development of density functional theory has led to the consideration of computational
chemistry in the design and development of interactions of new drugs in the gas phase with nanocarriers.
In the present study, the interaction of ibuprofen with alginic acid (as a nanocarrier) has been
investigated using density functional theory (DFT) in the gas phase (M06-2X/6-31+G*). A study on
the effects of ibuprofen’s interaction with the compounds present in alginic acid has been conducted,
focusing on the electronic properties, the chemical shift tensors, and the natural bond orbital. Based on
the results of UV spectra, the compound 6-thioguanine has been found to be changed into an alginic
acid/ibuprofen complex. The quantum theory of atoms in molecules showed the interaction of ibuprofen
to be mainly driven by non-covalent bonds with alginic acid during complex formation. A
hydrogen bond has been found to be formed between the oxygen atoms of alginic acid and ibuprofen's
hydrogen atoms. Consequently, alginic acid has been used for delivering ibuprofen to diseased cells.
Synthesis and Development of a Nonaflate Ester in the Large-Scale
Preparation of 3-Deoxymorphine
Authors: Ruda Antonio M. , Moseley Jonathan D. 
Published: January 2024

Abstract:
A series of novel activated esters of morphine were synthesized as alternatives to the triflate
ester and submitted to hydrogenolysis conditions. Of these, only the novel nonaflate ester could
be transformed with full conversion into the useful intermediate, 3-deoxymorphine, which was isolated
in good yield and high purity without chromatography. This conversion proceeded significantly
faster than for the triflate ester and with synthesis of the intermediate nonaflate at much reduced cost,
an important factor for the large-scale preparation of 3-deoxymorphine in drug development projects.
Number of People with Type 2 Diabetes Mellitus in 2035 and 2050: A Modelling Study in 188 Countries
Authors: Guzman-Vilca Wilmer Cristobal , Carrillo-Larco Rodrigo M. 
Published: January 2024

Background:
Future demographic changes will increase the number of people living
with non-communicable diseases. We projected the number of people with type 2 diabetes mellitus
(T2DM) in 2035 and 2050 at the global and country levels.

Methods:
We pooled T2DM prevalence estimates from the Global Burden of Disease Study and
population estimates from the United Nations for 188 countries. We computed the absolute
number of people with T2DM in 2020 and predicted the future number in 2035 and 2050 under
four scenarios for the T2DM prevalence: 1) It held constant, 2) It increased by 50%, 3) It decreased
by 10%, and 4) It followed 1990-2019 country-specific past trends.

Results:
The global number of people with T2DM was 445 million in 2020, and it is projected to
increase in 2050 to 730 million if prevalence remains unchanged, 1,095 million if prevalence increases
by 50%, 657 million if prevalence decreases by 10%, and 1,153 million if prevalence follows
country-specific 1990-2019 past trends. Under all scenarios, Sub-Saharan Africa and lowincome
countries had the highest relative increase in the number of people with T2DM. The
share of people with T2DM aged <60 years is expected to drop from 5 out of 10 in 2020 to 4 out
of 10 people in 2050 under all scenarios.

Conclusions:
There will be a massive growth in the number of people living with T2DM, and
low-income countries and countries in Sub-Saharan Africa will be the most affected. Health systems
must be strengthened to ensure optimal care for the future population with T2DM.
Gut Microbiota and Insulin Resistance: Understanding the Mechanism of Better Treatment of Type 2 Diabetes Mellitus
Authors: Al-Busaidi Alsalt , Alabri Omer , Alomairi Jaifar , ElSharaawy Ahmed , Al Lawati Abdullah , Al Lawati Hanan , Das Srijit 
Published: January 2024

:
Gut microbiota refers to the population of trillions of microorganisms present in the
human intestine. The gut microbiota in the gastrointestinal system is important for an individual’s
good health and well-being. The possibility of an intrauterine colonization of the placenta
further suggests that the fetal environment before birth may also affect early microbiome development.
Various factors influence the gut microbiota. Dysbiosis of microbiota may be associated
with various diseases. Insulin regulates blood glucose levels, and disruption of the insulin signaling
pathway results in insulin resistance. Insulin resistance or hyperinsulinemia is a pathological
state in which the insulin-responsive cells have a diminished response to the hormone compared
to normal physiological responses, resulting in reduced glucose uptake by the tissue cells. Insulin
resistance is an important cause of type 2 diabetes mellitus. While there are various factors
responsible for the etiology of insulin resistance, dysbiosis of gut microbiota may be an important
contributing cause for metabolic disturbances. We discuss the mechanisms in skeletal
muscles, adipose tissue, liver, and intestine by which insulin resistance can occur due to gut microbiota's
metabolites. A better understanding of gut microbiota may help in the effective treatment
of type 2 diabetes mellitus and metabolic syndrome.
The Value of Microbiome-targeted Therapy on Lipid Indices of Patients with Type 2 Diabetes Mellitus: An Umbrella Meta-analysis of Randomized Controlled Trials
Authors: Keivanlou Mohammad-Hossein , Amini-Salehi Ehsan , Hassanipour Soheil , Zare Reza , Mohammadi-Vajari Erfan , Hashemi Mohammad , Salari Arsalan , Porteghali Parham 
Published: January 2024

Background:
Type 2 diabetes mellitus (T2DM) is considered a global health challenge with increasing prevalence in recent years. One of the key elements in managing T2DM
patients is controlling their lipid profile. Recent studies suggest microbiome-targeted therapy
(MTT) as a treatment strategy for enhancing lipid profiles in these patients.

Objective:
The current study aimed to investigate the impact of MTT on lipid indices of T2DM
patients by performing an umbrella approach.

Methods:
Three international databases including PubMed, Scopus, and Web of Sciences were
searched from inception up to April 2023 to find meta-analyses evaluating the impact of MTT
(prebiotics, probiotics, and synbiotics) on the lipid profile of T2DM patients. Two independent
researchers extracted data from the relevant meta-analyses. To find the source of heterogeneity
various subgroup analyses were performed. Comprehensive Meta-Analyses (CMA) software
version 3 was utilized for the final analysis

Results:
Based on the results of the current study MTT had a significant effect on total cholesterol
(TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) (ES: -
0.092; 95%CI: -0.111, -0.074; P< 0.001, ES: -0.109; 95%CI: -0.137, -0.081; P< 0.001, ES: -0.036;
95%CI: -0.068, -0.005; P= 0.024, ES: 0.109; 95%CI: 0.056, 0.162; P<0.000, respectively). In subgroup analysis, probiotics showed the most substantial effect on all lipid biomarkers.

Conclusion:
This research has provided promising insights into the potential impact of MTT on
lipid levels in patients diagnosed with T2DM. Notably, MTT had the greatest impact on HDL
levels, followed by TG, TC, and LDL. As a result of our study, MTT is recommended as an adjunctive therapeutic option for T2DM treatment due to its capability to regulate lipid profiles.
Understanding Fertile Window: A Key to Pregnancy as well as Contraception
Authors: Tiwari Prashant , Kadiri Sunil Kumar , Dubey Priyanka , Singh Dilpreet , Khobragade Deepak Shamrao , Sahu Pratap Kumar 
Published: January 2024

:
Though population explosion is a major problem of the world today, infertility also exists
and needs attention. Understanding reproductive health, the menstrual cycle, and adopting natural
methods by couples can manage both fertility as well as infertility. During the preparation of
the present review article, several search engines, such as Research Gate, Google Scholar, shodhganga,
Scopus, emerging source citation index, chemical abstract services, academic journals
database, open access medical journals, scirus, journal informatics, and various referred and nonreferred
journals were used for the extraction of scientific information. Hence, this article has
been prepared meticulously, which would help married couples in adopting an effective life plan
for managing their reproductive activities. It explains about means of avoiding unwanted pregnancies
using some naturally proven methods available. It also addresses issues related to infertility.
Understanding ovulation symptoms and the fertile window is the key to determining the right time
for intercourse in order to avoid or plan pregnancy. The ovulation technique uses the indicators of
ovulation to determine the fertile window. A rise in body temperature and changes in cervical mucus
(wet, clear, slippery) are the best indicators of ovulation. Understanding the concept of the fertile
window enables women to strategically plan the timing of intercourse in order to either facilitate
conception or prevent it.