bluuebunny/crossref_metadata_2025 huggingface dataset:
A Solidary Society: From History to Present
Authors:   Ufa University of Science and Technology, Frolova I. V. , Lukmanova R. K. ,   Ufa University of Science and Technology, Frolov K. A. ,   Ufa University of Science and Technology
Published: January 2024

The article provides a description of the All-Russian scientific and practical conference “Solidarity Society as an Ideal and a Project: History and Modernity”, held on March 16, 2023 in Ufa. The Institute of History and Public Administration of the Ufa University of Science and Technology organized the conference. It is the part of the project “Solidarity society: from discursive analysis to social practice”, supported by the Russian Science Foundation. The focus of the conference participants was the consideration and comprehension of complex and debatable issues related to the search for the consolidating foundations of modern Russian society. Researchers have pondered what constitutes solidarity and the social ideal in historical retrospect; how the problem of solidarity is presented in Russian and world social thought; whether it is possible to visualize the ideas of solidarity in art. Key issues were presented in the reports of the plenary part and then discussed in the format of round tables, lectures, discussions, scientific sessions of students. According to participants, the mission of social science and the humanities is to combine the ideas of solidarity with the fate of the country. Thus, it is necessary to consider solidarity in the historical perspective, primarily the Russian one. The integration of social and humanitarian knowledge is capable of synthesizing a stereoscopic vision of the manifestations of solidarity in public life.
Improving Photocleavage Efficiency of Photocleavable Protein for
Antimicrobial Peptide Histatin 1 Expression
Authors: Zhou Nana , An Tai , Zhang Yuan , Zhao Guomiao , Wei Chao , Shen Xuemei , Li Fan , Wang Xiaoyan
Published: January 2024

Background:

Antimicrobial peptides (AMPs) are promising alternative agents for
antibiotics to overcome antibiotic resistance problems. But, it is difficult to produce large-scale antimicrobial research due to the toxicity towards expression hosts or degradation by peptidases in
the host. Therefore, heterologous recombinant expression of antimicrobial peptides has always
been a challenging issue.

Objective:

To overcome toxicity to the expression host and low expression level, a new photocleavable protein fusion expression method for antimicrobial peptides is provided.

Methods:

Through directed evolution and high throughput screening, a photocleavable protein mutant R6-2-6-4 with a higher photocleavage efficiency was obtained. The DNA coding sequence of
antimicrobial peptide Histatin 1 was fused within the sequence of R6-2-6-4 gene. The fusion gene
was successfully expressed in Escherichia coli expression system.

Results:

Antimicrobial peptide Histatin 1 could be successfully expressed and purified by fusing
within PhoCl mutant R6-2-6-4. The antimicrobial activity was rarely affected, and the MIC value
was 33 ug/mL, which was basically equivalent to 32 ug/mL of the chemically synthesized Histatin
1. After amplification in a 5 L fermenter, the expression of PhoCl mutant (R6-2-6-4)-Histatin1 improved up to 87.6 mg/L in fermenter, and Histatin1 obtained by photocleavage also could up to 11
mg/L. The prepared Histatin1 powder remained stable when stored at 4oC for up to 4 months without any degradation. In addition, the expression and photocleavage of β -Defensin105 and Lysostaphin verified the certain universality of the PhoCl mutant fusion expression system.

Conclusion:

Antimicrobial peptides Histatin 1, β -Defensin 105 and Lysostaphin were successfully expressed and purified by photocleavable protein mutant. This may provide a novel strategy to
express and purify antimicrobial peptides in the Escherichia coli expression system.
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.
Natural and Synthetic Coumarins as Potential Drug Candidates against SARS-CoV-2/COVID-19
Authors: da Silva Santos Iara , Magalhaes Leticia Oliveira , Marra Roberta Katlen Fusco , da Silva Lima Camilo Henrique , Hamerski Lidilhone , Albuquerque Magaly Girao , da Silva Barbara Vasconcellos
Published: January 2024

COVID-19, an airborne disease caused by a betacoronavirus named SARS--
CoV-2, was officially declared a pandemic in early 2020, resulting in more than 770 million
confirmed cases and over 6.9 million deaths by September 2023. Although the introduction
of vaccines in late 2020 helped reduce the number of deaths, the global effort to
fight COVID-19 is far from over. While significant progress has been made in a short period,
the fight against SARS-CoV-2/COVID-19 and other potential pandemic threats
continues. Like AIDS and hepatitis C epidemics, controlling the spread of COVID-19
will require the development of multiple drugs to weaken the virus's resistance to different
drug treatments. Therefore, it is essential to continue developing new drug candidates
derived from natural or synthetic small molecules. Coumarins are a promising
drug design and development scaffold due to their synthetic versatility and unique physicochemical
properties. Numerous examples reported in scientific literature, mainly by in
silico prospection, demonstrate their potential contribution to the rapid development of
drugs against SARS-CoV-2/COVID-19 and other emergent and reemergent viruses.
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

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

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

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

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.
The Potential Therapeutic Applications of CRISPR/Cas9 in the Treatment of Gastrointestinal Cancers
Authors: Mehrabadi Shima , Izadi Faezeh Salmani , Pasha Shiva , Pourali Roozbeh , Khazaei Majid , Hassanian Seyed Mahdi , Ferns Gordon A , Avan Amir
Published: January 2024

Gastrointestinal (GI) cancer is one the most prevalent types of cancer.
Despite current chemotherapy's success, patients with GI cancer continue to have a
dismal outcome. The onset and progression of cancer are caused by alterations and
the abnormal expression of several families of genes, like tumor-suppressor genes,
oncogenes, and chemotherapy-resistant genes. The final purpose of tumor therapy is
to inhibit cellular development by modifying mutations and editing the irregular
expression of genes It has been reported that CDH1, TP53, KRAS, ARID1A, PTEN,
and HLA-B are the commonly mutated genes in GI cancer. Gene editing has become
one potential approach for cases with advanced or recurrent CRC, who are nonresponsive
to conventional treatments and a variety of driver mutations along with
progression cause GI progression. CRISPR/Cas9 technique is a reliable tool to edit the
genome and understand the functions of mutations driving GI cancer development.
CRISPR/Cas9 can be applied to genome therapy for GI cancers, particularly with
reference to molecular-targeted medicines and suppressors. Moreover, it can be used
as a therapeutic approach by knocking in/out multiple genes. The use of CRISPR/
Cas9 gene editing method for GI cancer therapy has therefore resulted in some
improvements. There are several research works on the role of CRISPR/Cas9 in
cancer treatment that are summarized in the following separate sections. Here, the use
of CRISPR/Cas9-based genome editing in GI and the use of CRISPR/Cas9 is
discussed in terms of Targeting Chemotherapy Resistance-related Genes like; KRAS,
TP53, PTEN, and ARID1A.
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

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

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.
Theaflavins Induce Autophagy in Ehrlich’s Ascites Carcinoma Cells both
In vivo and In vitro
Authors: Ghosh Arijit Kumar , Verma Aanchal , Majumder Debabrata , Maiti Debasish , Choudhuri Tathagata , Banerjee Antara , Saha Samiran
Published: January 2024

Aims:

To investigate the efficacy of Theaflavins to induce autophagy and its tumoricidal activity towards Ehrlich’s Ascites Carcinoma cells.

Background:

The apoptosis-inducing role of Theaflavins against cancer is reported. Autophagy,
a cellular mechanism under stress, occurs either as a survival process or Type-II programmed-cell
death in the presence/absence of apoptosis. The report of Theaflavins inducing autophagy against
cancer is poor.

Objective:

Here, for the first time, the investigation for the anti-tumor efficacy of Theaflavins via
autophagy in EAC was attempted.

Methods:

EAC-bearing mice were treated orally with Theaflavins (10 mg/kg b.w.) every alternate
day with a total of 27 doses. Body weight, tumor volume and survivability were recorded. Tumoricidal
and cellular dehydrogenase activity, in vivo and in vitro, were studied using Trypan-blue
exclusion and MTT assay respectively. Theaflavins-treated EAC cells were subjected to Monodansylcadaverine-
staining. LC3II turnover and LC3I conversion were detected by western blotting.
Apoptosis up to 12 h TF-treatment was estimated by AnnexinV binding.

Results:

This is the first report of Theaflavins inducing autophagy in EAC cells in vivo and in
vitro. Oral Theaflavins treatment restricted excessive body-weight increase due to tumors, reduced
tumor volume, and increased survivability of tumor-bearing mice. Theaflavins caused EAC
cell death (~8% in vitro, ~30% in vivo), significantly reduced metabolic activity, and created conspicuous
vacuolization in surviving cells. Resultant vacuoles (in vitro, 6 h) were marked as autophagosomes
by Monodansylcadaverine-staining. Autophagy was confirmed by LC3II augmentation.
No significant apoptosis was observed up to 12 h TF-treatment in vitro.

Conclusion:

Theaflavins were efficient inducing autophagy and Type-II PCD in EAC cells. Notably,
Theaflavins induced autophagy prior to apoptosis in vitro.
Metabolite Profiling and in silico Studies to Elucidate the
Anti-inflammatory Properties of Pterocarpus milbreadii
Authors: Aba Patrick Emeka , Odugbo Ismaila Onuche
Published: January 2024

Background::

Pterocarpus milbreadii (PM), called Rosewood in English, is a leafy vegetable
used in preparing soup and has also proven medicinal.

Objective::

This study aimed to evaluate the most abundant compound in the ethylacetate fraction of
PM using Gas Chromatography-mass Spectrometry (GC-MS) and docking it against cyclooxygenase
isoenzymes.

Methods::

The PM leaves were extracted with ethyl acetate using the cold maceration method. The
extract was subjected to GC-MS assay. The spectra obtained were matched with NIST 17. AutoDock
Vina was used to perform the molecular docking of the most abundant compound of PM and cyclooxygenase.
Celecoxib was used as the standard ligand.

Results::

The results of the study revealed that the ethyl acetate leaf extract of PM contained different
phytochemicals, with hexadecenoic acid being the most abundant, with an intensity count of 9.5 x108
CPS. Docking of hexadecenoic acid and Celecoxib with COX-2 yielded binding energies of -6.7 and
-7.7 kcal/mol, respectively, while with COX-1, the binding energies of -6.3 and -9.8 kcal/mol were
respectively recorded. Hexadecenoic acid interacted with both COX-1 and COX-2 largely via Van
der waals and pi-Alkyl bonds. Celecoxib made conventional hydrogen, carbon-hydrogen, halogen,
pi-sigma, pi-alkyl interactions with the cyclooxygenase isoenzymes.

Conclusion::

It was concluded that hexadecenoic acid was the predominant phytochemical in the
ethylacetate leaf extract of PM. The hexadecanoic acid ligand produced a better inhibitory effect on
COX-2 compared to COX-1.
Molecular Mechanism Analysis of the Effect of Hederagenin Combined with L-OHP on Chemosensitivity of AGS/L-OHP Based on Network
Pharmacology
Authors: Tang Hongyue , Wang Chao , Xing Chenhao , liang Guoxin , Guo Chang , Liu Xin , Li YanJie , Zhang Mingming
Published: January 2024

Aims and Objectives:

This study aimed to evaluate the pharmacological mechanism
of Hederagenin (HD) combined with oxaliplatin (L-OHP) in treating gastric cancer (GC)
through network pharmacology combined with experimental verification.

background:

Gastric cancer (GC) is the world’s most common gastrointestinal cancer[1]. This malignancy is of challenge to be eradicated by surgical operation since most diagnosed patients have developed into the advanced stage. Chemotherapy is a crucial part of the comprehensive treatment for GC, despite that the potential drug resistance may reduce the therapeutic efficacy[2,3]. Oxaliplatin (L-OHP) is the third-generation platinum-based antineoplastic drug, which has been widely used for GC treatment because of its excellent performance compared with many other chemotherapeutic drugs such as cisplatin[4]. However, previous studies have reported that GC cells still show some resistance to L-OHP .

Material and Methods:

Network pharmacology methods were used to screen potential targets
for HD, L-OHP, and GC-related targets from public databases, and the intersection of the three
gene sets was taken. Cross genes were analyzed through protein-protein interaction (PPI) networks
to predict core targets, and related pathways were predicted through GO and KEGG enrichment
analysis. The experimental results were verified by the in vitro experiments. HD was
applied on AGS/L-OHP cells, and then cellular chemosensitivity and the expressions of P-gp,
Survivin, Bcl-2, p-Akt, and p-PI3K genes were detected. Wound assay and Transwell Chamber
assay were employed to detect the effect of HD on AGS/L-OHP cells. Nude mice xenograft
models transfected using AGS/L-OHP cells were also treated with HD in order to verify the
results. The size and weight of the tumor, as well as the expressions of P-gp, Survivin, Bcl-2, p-
Akt and p-PI3K genes, were also measured.

Results:

KEGG analysis showed that the anti-gastric cancer effect of HD was mediated mainly
by PI3K-Akt signaling pathways. The PI3K-Akt signaling pathway containing more enriched
genes may play a greater role in anti-gastric cancer. It was observed that for AGS/L-OHP cells
jointly treated with HD and L-OHP, their activity, migration and invasion were significantly
lower than those treated only using HD or L-OHP group. Moreover, expressions of p-Akt, p-
PI3K, Bcl-2, P-gp, and Survivin for the HD+L-OHP group decreased significantly. Results of
the in vivo experiments showed that the sizes and weights of tumors in the HD+L-OHP group
were the lowest compared to the HD group and L-OHP group.

Conclusion:

Our findings suggest that HD may reduce the resistance of AGS/L-OHP cells to LOHP
by regulating the PI3K/Akt signaling pathway.
Targeting Epigenetic Modifiers: Promising Strategies for Cancer Therapy and Beyond
Authors: Chanchal Dilip Kumar , Porwal Prateek , Mittal Nidhi
Published: January 2024

:

Epigenetic changes are important for controlling how genes are expressed and how cells
work, and their misregulation has been linked to many diseases, including cancer. Targeting epigenetic
modifiers has become a promising way to treat cancer, and it may also be useful outside of
oncology. This review article goes into detail about the rapidly changing field of epigenetic-based
therapies, with a focus on how they are used to treat cancer. We discuss in-depth the main epigenetic
changes seen in cancer, such as DNA methylation, changes to histones, and dysregulation of noncoding
RNA, as well as their roles in tumour growth, metastasis, and drug resistance. Epigenetic
drugs and small molecule inhibitors that target epigenetic enzymes and reader proteins have shown a
lot of promise in both preclinical and clinical studies on different types of cancer. We show the most
recent evidence that these epigenetic therapies work and look into how they might be used in combination
with other treatments. We talk about new research into the therapeutic potential of epigenetic
modifiers in diseases other than cancer, such as neurological disorders, autoimmune diseases, and
heart conditions. Even though there is a lot of potential for therapy, there are still problems, such as
side effects and differences between patients. We talk about the work that is still being done to get
around these problems and explain new ways to deliver epigenetic-based interventions that are more
precise and effective. For epigenetic-based therapies to be used in clinical settings, it is important to
understand how they work and how they interact with other types of treatment. As the field moves
forward, we try to figure out where it is going and what it means to target epigenetic modifiers in
cancer therapy and other areas of disease. This review looks at the role of epigenetic modulation in
shaping the landscape of precision medicine and its possible effects on human health from a broad
and forward-looking point of view.
Enhancing Spermatogenesis in Non-obstructive Azoospermia Through Mesenchymal Stem Cell Therapy22
Authors: Margiana Ria
Published: January 2024

:

Stem cells hold great promise as novel and encouraging therapeutic tools in the treatment
of degenerative disorders due to their differentiation potential while maintaining the capability
to self-renewal and their unlimited ability to divide and regenerate tissue. A variety of different
types of stem cells can be used in cell therapy. Among these, mesenchymal stem cell (MSC) therapy
has gradually established itself as a novel method for treating damaged tissues that need restoration
and renewal. Male infertility is an important health challenge affecting approximately
8-12% of people around the world. This abnormality can be caused by primary, congenital, acquired,
or idiopathic reasons. Men with no sperm in their semen have a condition called azoospermia,
caused by non-obstructive (NOA) causes and post-testicular obstructive causes. Accumulating
evidence has shown that various types of MSCs can differentiate into germ cells and improve
spermatogenesis in the seminiferous tubules of animal models. In addition, recent studies in animal
models have exhibited that extracellular vesicles derived from MSCs can stimulate the progression
of spermatogenesis and germ cell regeneration in the recipient testes. In spite of the fact
that various improvements have been made in the treatment of azoospermia disorder in animal
models by MSC or their extracellular vesicles, no clinical trials have been carried out to test their
therapeutic effect on the NOA. In this review, we summarize the potential of MSC transplantation
for treating infertility caused by NOA.
Preparation, Characterization, and Anticancer Activity Assessment of Chitosan/TPP Nanoparticles Loaded with Echis carinatus Venom
Authors: Kancha Maral Mahboubi , Mehrabi Mohsen , Bitaraf Fatemeh Sadat , Vahedi Hamid , Alizadeh Morteza , Bernkop-Schnürch Andreas
Published: January 2024

Aims and Background:

Echis carinatus venom is a toxic substance naturally produced by special glands in this snake species. Alongside various toxic properties, this venom has been used for its therapeutic effects, which are applicable in treating various cancers (liver, breast, etc.).

Objective:

Nanotechnology-based drug delivery systems are suitable for protecting Echis carinatus venom against destruction and unwanted absorption. They can manage its controlled transfer and absorption, significantly reducing side effects

Methods:

In the present study, chitosan nanoparticles were prepared using the ionotropic gelation method with emulsion cross-linking. The venom's encapsulation efficiency, loading capacity, and release rate were calculated at certain time points. Moreover, the nanoparticles' optimal formulation and cytotoxic effects were determined using the MTT assay.

Results:

The optimized nanoparticle formulation increases cell death induction in various cancerous cell lines. Moreover, chitosan nanoparticles loaded with Echis carinatus venom had a significant rate of cytotoxicity against cancer cells.

Conclusion:

It is proposed that this formulation may act as a suitable candidate for more extensive assessments of cancer treatment using nanotechnology-based drug delivery systems.
Ameliorating Gonorrhea: Recent Therapeutic Adaptations and Scope to
Improve its Prevailing Condition
Authors: Bishi Munyaradzi Amon , Kaur Palwinder , Vyas Manish , Sharma Sandeep
Published: January 2024

Background::

Gonorrhea is a sexually transmitted infection (STI) caused by the bacteria
Neisseria gonorrhoeae. According to recent research, the prevalence of gonorrhea has been increasing
in many parts of the world, with some areas reporting high rates of antibiotic resistance. In the
United States, the Centers for Disease Control and Prevention (CDC) reported that the number of
reported gonorrhea cases increased by 56% between 2015 and 2019. Globally, the World Health Organization
(WHO) estimated that there were 87 million new cases of gonorrhea in 2016, with the
highest burden of infection in low- and middle-income countries. Research has also shown that gonorrhea
is becoming increasingly resistant to conventional antibiotics, increasing the prevalence of
gonorrhea. This raises concerns and challenges in disease management.

Objectives::

The present review gives updated insight on the current state of the disease, challenges,
and shortcomings of existing approaches along with the modern and alternative direction like vaccine
development, its challenges, and scope to confront the existing state of drug resistance and increased
rate of incidence. Alternative strategies like immunotherapy and phage therapy along with recent
antibiotics researched for the treatment of gonorrhea.

Conclusion::

The review provides a thorough insight into the current state of the disease and various
available methods used currently and recommended by WHO. To overcome disease prevalence, various
alternate therapies are coming into the limelight. However, scientists and researchers show a lack
of interest in the drug development and research of gonorrhea, due to less commercial scope, lack of
funding, and limited scope in the scientific scenario. These hurdles need to be overcome to meet the
WHO vision of reducing gonorrhea by 90% by 2030. So, there is a need to optimize the drug therapy
(optimizing dosing schedule, and precision monitoring) to reduce the chance of drug resistance. Also,
there is a wide scope for drug and therapeutic system development.
Uniparental Disomy as a Mechanism for Combined Oxidative Phosphorylation
Deficiency Associated with MRPS34 Gene
Authors: Soares Marta P. , Travessa André M. , Custódio Sónia , Pereira Carla , Pinto Patrícia , Sousa Ana Berta
Published: January 2024

Introduction:

Mitochondrial oxidative phosphorylation (OXPHOS) is a cellular process
that generates most of the cellular energy required by the body. Disorders affecting
OXPHOS are multisystem diseases caused by pathogenic variants in more than 50 genes. In
2017, biallelic variants in the MRPS34 gene were shown to cause combined oxidative phosphorylation
deficiency type 32 (COPD32) (OMIM#617664); however, only 7 patients have
been reported in the literature up to this moment. COPD32 is characterized mainly by a severe
Leigh-like syndrome.

Methods:

Whole-exome sequencing identified a homozygous pathogenic variant in the
MRPS34 gene, c.322-10G>A. Only the mother was heterozygous for this variant. SNP-array
analysis was performed, which revealed a region of absence of heterozygosity in variant 16q
with 9.8Mb, compatible with maternal uniparental disomy.

Results/Case Report:

We report the case of an 18-year-old female with unremarkable family
history. The pregnancy was complicated by oligohydramnios, and the neonatal period was unremarkable.
She evolved with low weight, mild-moderate developmental delay/intellectual disability,
and hypogonadotropic hypogonadism. On examination, she had slender habitus, joint
laxity, and kyphoscoliosis. The cardiac evaluation was normal, and the head MRI showed bilateral
olivary nucleus degeneration that was not confirmed subsequently. Extensive metabolic
studies documented only mild lactate and pyruvate elevation, and the chromosomal microarray
was normal.

Conclusion:

We have reported the case of the first patient with COPD32 due to partial maternal
uniparental disomy of chromosome 16, being first in Portugal and seventh in the literature. Contrarily
to previous patients, who died in the first months of life or survived with severe DD/ID,
and had a Leigh-like syndrome, this case is significantly milder, contributing to a better characterization
of the phenotypic spectrum. Recurrence risk is unexpectedly low in this instance. This
case illustrates the importance of segregation analysis in patients with homozygous recessive
mutations.