bluuebunny/crossref_metadata_2025_split huggingface dataset:
PKN2 signalling induces stromal cell protrusions to preserve lymph node structural integrity
Authors: Acton Sophie , Millward Lindsey , Benjamin Agnesska , Makris Spyridon , Horsnell Harry , Menezes Shinelle , Shewring Daniel , Tape Christopher , Saez Pablo , Cameron Angus , de Winde Charlotte 
Published: August 2024

Abstract

Secondary lymphoid tissues develop specialized stromal networks to facilitate immune cell communication and efficient activation of adaptive immunity. This stromal architecture is robust, maintaining topology throughout extensive remodelling and tissue expansion in response to immune challenge. We have previously reported that cytoskeletal mechanics of the fibroblastic reticular cell (FRC) networks determine tissue tension, and that increased tension initiates stromal proliferation required for lymph node growth. However, it is not known how FRCs mechanistically reshape the stromal network to preserve integrity through the early phases of inflammation. Here, we find a signalling mechanism which coordinates reduced FRC contractility and induction of stromal cell protrusions. RhoA/C GTPase activity is blocked in FRCs to inhibit actomyosin contractility upon contact with CLEC-2+ dendritic cells (DCs) and binding to podoplanin+ stroma. We now find that an additional Rho GTPase target, the PKC family kinase PKN2, regulates activity of myristoylated alanine-rich protein kinase C-substrate (MARCKS). FRCs use MARCKS to generate protrusions in response to DC contact. We tested this mechanism in vivo and found that PKN2 knock-out lymph nodes are unable to regulate MARCKS and show severely disrupted stromal architecture during lymph node expansion. We now present a mechanism of stromal/immune cell crosstalk which actively induces FRC protrusions – an essential component of lymph node remodelling – to maintain tissue integrity during an adaptive immune response.
In silico analysis of the anti-inflammatory activity of curcuminoids and/or curcumin metabolites on Cox-1 and Cox-2
Authors: Mbadiko Clément , Ngbolua Koto-te-Nyiwa , Bongo Gédéon , Matondo Aristote , Kilembe Jason , Nzundu Jean-Paul , Ngombe Nadège , Kapepula Paulin , Mbemba Théophile , Mpiana Pius 
Published: August 2024

Abstract

Background
The present work involved a comparative in silico analysis of the action of curcuminoids and curcumin metabolites against cyclooxygenases 1 and 2. The Protein Data Bank (PDB) was used to obtain the target proteins and Discovery studio 2021, PyRx, ChemDraw Professional 16.0 or the PubChem search engine were used during in silico screening.
Results
The in silico analyses revealed that all the ligands analyzed form stable complexes with the Cox-1 and Cox-2 receptors, which are involved in anti-inflammatory activity. The complexation energy of the ligands with Cox-1 ranged from − 7.2 to -8.8 kcal/mol. The complexation energy of Cox-2 and the ligands analyzed ranged from − 5.2 to -6.4 kcal/mol, predicting a high affinity between the ligands analyzed and Cox-1 compared with Cox-2. In addition, the ligands analyzed formed thermodynamically stable complexes with Cox-1 in the majority of cases compared to the reference molecules analyzed (aspirin: -6.2 Kcal/mol and ibuprofen: -7.2 Kcal/mol). Bisdemethoxycurcumin, curcumin sulphate, curcumin, cyclocurcumin, demethoxycurcumin, dihydrocurcumin, hexahydrocurcumin and tetrahydrocurcumin formed very stable bonds with Cox-1 with interaction enthalpies of -8, 8 Kcal/mol, -8.7 Kcal/mol, -8.6 Kcal/mol, -8.3 Kcal/mol, -8.3 Kcal, -8.0 Kcal/mol, -7.9 Kcal/mol and − 7.8 Kcal/mol respectively. Moreover, most of the ligands analyzed formed thermodynamically stable bonds with Cox-2 compared with the reference molecules. The binding enthalpies were − 6.4 Kcal/mol, -6.1 Kcal/mol; -6.1 Kcal/mol, -5.9 Kcal/mol, -5.9 Kcal/mol, -5.7 Kcal/mol, -5.6 Kcal/mol and − 5.5 Kcal/mol for cyclocurcumin, bisdemethoxycurcumin, demethoxycurcumin, curcumin, curcumin sulphate, glucuronocurcumin, dihydrocurcumin and tetrahydrocurcumin respectively; compared with 4.5 Kcal/mol for the complex formed with aspirin and − 5.4 Kcal/mol for that formed with ibuprofen.
Conclusion
Curcuminoids can individually or synergistically inhibit the action of Cox and act as anti-inflammatory agents, curcumin metabolites can also bind to the catalytic sites of Cox 1 and 2 and compete with arachidonic acid, the natural substrate of Cox.
Investigation of Kinetic and Thermodynamic Parameters of Sapodilla Leaves Pyrolysis Using Coats Redfern Model
Authors: Asif Muhammad , Tariq Rumaisa , Bilal Muhammad , Mannan Hafiz Abdul , Kanwal Sumaira , Rauf Abdul , Raza Faisal , Zeb Hassan 
Published: August 2024

Abstract

The determination of the energy potential of indigenous biomass waste is primarily the focus of every country in its quest to meet the energy demand via clean and sustainable sources. The objective of the current study is to investigate the thermo-kinetic behavior of the sapodilla leaves with thermogravimetric analysis to analyze its potential utilization for energy production through the thermochemical conversion process. Sapodilla leaves were dried, pulverized, and heated non-isothermally from room temperature to 900°C at different heating rates in an inert environment. Thermogravimetric results indicated that the Sapodilla leaves pyrolysis is divided into three stages. The Coats-Redfern integral model was applied in the 2nd and 3rd stages to estimate the numerical value of thermo-kinetic parameters, using five major solid-state reaction mechanisms. The low-temperature stable components (LTSC) degraded in the temperature range of 250–550°C while high-temperature stable components (HTSC) decomposed in the temperature range of 550–850°C. About 45-50wt% degradation in the first temperature range of 250–550°C and about 15-17wt% degradation was observed in 2nd degradation temperature range of 550–900°C. According to the results, the diffusion model D3showed the highest regression coefficient in the first degradation stage while in the second degradation stage, the nucleation models N1.5and N2showed the highest regression coefficient. The activation energy of sapodilla leaves degradation was found in the range between 30–32 kJmol− 1for best-fitted models in low-temperature regions and 8–12 kJmol− 1in high-temperature regions. The positive value of change in enthalpy and Gibbs free energy showed that the reaction is endothermic while the negative value of entropy showed the more regular arrangement of the products. Thermo-kinetic behavior of sapodilla leaves hints toward their huge potential for bio-oil and syngas production through pyrolysis and gasification processes.
Macromolecular Polymer Based Complexes: A Diverse Strategy for the Delivery of Nucleotides
Authors: Singh Dilpreet 
Published: August 2024

:
This review explores the burgeoning field of macromolecular polymer-based complexes,
highlighting their revolutionary potential for the delivery of nucleotides for therapeutic applications.
These complexes, ingeniously crafted from a variety of polymers, offer a unique solution to
the challenges of nucleotide delivery, including protection from degradation, targeted delivery,
and controlled release. The focus of this report is primarily on the design principles, encapsulation
strategies, and biological interactions of these complexes, with an emphasis on their biocompatibility,
biodegradability, and ability to form diverse structures, such as nanoparticles and micelles. Significant
attention is paid to the latest advancements in polymer science that enable the precise
tailoring of these complexes for specific nucleotides, such as DNA, RNA, and siRNA. The review
discusses the critical role of surface modifications and the incorporation of targeting ligands in enhancing
cellular uptake and ensuring delivery to specific tissues or cells, thereby reducing off-target
effects and improving therapeutic efficacy. Clinical applications of these polymer-based delivery
systems are thoroughly examined with a focus on their use in treating genetic disorders, cancer,
and infectious diseases. The review also addresses the challenges and limitations currently
faced in this field, such as scalability, manufacturing complexities, and regulatory hurdles. Overall,
this review provides a comprehensive overview of the current state and future prospects of
macromolecular polymer-based complexes in nucleotide delivery. It underscores the significance
of these systems in advancing the field of targeted therapeutics and their potential to reshape the
landscape of medical treatment for a wide range of diseases.
Preparation and Characterization of Nanostructured Lipid Carriers (NLCs) Containing Glycyrrhiza glabra Extract for the Treatment of Skin Hyperpigmentation
Authors: Hoseinsalari Afsaneh , Atapour-Mashhad Hoda , Asili Javad , Tayarani-Najaran Zahra , Mohtashami Leila , Khanavi Mahnaz , Vazirian Mahdi , Akbari Javar Hamid , Niknam Somayeh , Golmohammadzadeh Shiva , Ardekani Mohammad Reza Shams 
Published: August 2024

Purpose:
This study aimed to prepare, characterize, and in vitro and in vivo evaluate a novel
nanostructured lipid carriers (NLCs) formulation containing two fractions of Glycyrrhiza glabra L. (licorice)
extract for the treatment of hyperpigmentation.

Methods:
Two fractions, one enriched with glabridin (FEG) and the other enriched with liquiritin (FEL), were
obtained by partitioning the methanol (MeOH) extract of licorice roots with ethyl acetate (EtOAc) and partitioning
the EtOAc fraction with butanol (n-BuOH) and water. The quantities of glabridin (Glab) and liquiritin
(LQ) in the fractions were determined by high-performance liquid chromatography (HPLC). FEG and FEL
were loaded in different NLC formulations, and surface characterization and long-term stability were studied
using Dynamic Light Scattering (DLS). The best formulation was chosen for further surface characterization,
including Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC), and Fouriertransform
infrared (FTIR) spectroscopy. Moreover, entrapment efficiency percentage (EE%), in vitro drug release,
in vivo skin penetration, cytotoxicity on B16F10 melanoma cells, effect on melanin production, and anti-
tyrosinase activity were tested for the selected formulation.

Results:
Based on HPLC results, FEG contained 34.501 mg/g of Glab, and FEL contained 31.714 mg/g of
LQ. Among 20 different formulations, NLC 20 (LG-NLCs) showed desirable DLS results with a Z-average
size of 185.3 ± 1.08 nm, polydispersity index (PDI) of 0.229 ± 0.35, and zeta potential of -16.2 ± 1.13 mV. It indicated
good spherical shape, high EE% (79.01% for Glab and 69.27% for LQ), two-stage release pattern (an initial
burst release followed by sustained release), efficient in vivo skin penetration, and strong anti-tyrosinase
activity. LG-NLCs had acceptable physiochemical stability for up to 9 months and were non-cytotoxic.

Conclusion:
The LG-NLC formulation has revealed desirable surface characterization, good physiochemical
stability, efficient drug release pattern and in vivo penetration, and high EE%. Therefore, it can be a suitable
nanosystem for the delivery of licorice extract in the treatment of hyperpigmentation.
Down-Regulated JDP2 Attenuated Trophoblast Invasion and Migration in Preeclampsia by Inhibiting Epithelial-Mesenchymal Transition through the Wnt/β-Catenin Pathway
Authors: Jiang Ziyan , Huang Shiyun , Ying Tingting , Liu Lenan , Han Yufei , Feng Runrun , Sun Haiyan , Cao Ceng , Zuo Qing , Ge Zhiping 
Published: August 2024

Introduction:
Preeclampsia (PE) is an immensely prevalent condition that poses a significant
risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity
and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast
invasion and migration in the context of preeclampsia remains unclear.

Materials and Methods:
The present study aimed to investigate the differential expression of JDP2
between normal control and preeclampsia placentas through the use of quantitative polymerase
chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects
of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities
of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2
on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/β-catenin pathway.

Results:
In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited
a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison
to those of normal placentae. Impairment in migration and invasion was noted upon JDP2
down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression
in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays
were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin,
N-cadherin, and β-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating
the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/β-catenin signaling was observed
as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study.
IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells.

Conclusion:
Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in
preeclampsia by suppressing the EMT through the Wnt/β-catenin signaling pathway, thereby offering
a potential prognostic and therapeutic biomarker for this condition.
Joint Screening and Identification of Potential Targets of Nitazoxanide by Affinity Chromatography and Label-Free Techniques
Authors: Zhu Menghan , Qi Dongxia , Chen Dongliang , Ye Wenchong , Wang Xiaoyang , Wang Chunmei , Zhou Wen , Zhou Bin , Li Juan , Zhang Keyu 
Published: August 2024

Background:
Nitazoxanide not only exhibits a broad spectrum of activities against various pathogens infecting animals and humans but also induces cellular autophagy. Currently, the pattern of action and subcellular targets of nitazoxanide-induced cellular autophagy are still unclear.

Methods:
To identify potential targets of nitazoxanide in mammalian cells, we developed an af-finity chromatography system using tizoxanide, a deacetyl derivative of nitazoxanide, as a ligand. Affinity chromatography was performed using VERO cell extracts on tizoxanide-biotin, and the isolated binding proteins were identified by mass spectrometry. Candidate target proteins ob-tained using affinity chromatography were co-analysed with the drug affinity response target sta-bility method. Fluorescent probes obtained by coupling rhodamine B to nitazoxanide were used for intracellular localisation of the binding targets. Solvent-induced protein precipitation profiling and thermal proteome profiling were used to further validate the binding proteins.

Results:
The joint analysis of the drug affinity response target stability method and affinity chro-matography resulted in the screening of six possible candidate target proteins. Fluorescent probes localised the nitazoxanide-binding protein around the nuclear membrane. Molecular docking re-vealed that the binding proteins mainly formed hydrogen bonds with the nitro group of nitazoxa-nide. Solvent-induced protein precipitation profiling and thermal proteome profiling further vali-dated SEC61A, PSMD12, and PRKAG1 as potential target proteins of nitazoxanide.

Conclusion:
The data supports the idea that nitazoxanide is a multifunctional compound with multiple targets.
Indirubin as an AHR Ligand: A Combined Network Pharmacology and Experimental Approach to Psoriasis Therapy
Authors: Yang Lihong , Cheng Xueli , Li Qian , Liu Guandong , Lin Yu , Xu Muchen , Sun Wen , Liu Jing 
Published: August 2024

Background:
AHR and its signaling pathways are promising therapeutic targets for psoriasis.
Recent studies in traditional Chinese medicine have confirmed that Indirubin acts as an efficient
ligand of AHR, inhibiting the inflammatory response. Clarifying its mechanism of action remains
essential.

Objective:
This study uses bioinformatics to predict Indirubin’s potential molecular mechanism in
treating psoriasis and validate the results in animal models.

Methods:
Indirubin and psoriasis-related targets were screened using the TCMPSP, GeneCards, and
OMIM databases. Using the STRING database, a network was constructed and enriched for target
protein function. Imiquimod was used to validate the core targets in a psoriasis-like mouse model.

Results:
Network pharmacology suggested that indirubin targets pathways mainly involved in cancer,
inflammation, apoptosis, and other disease mechanisms, including PI3K-Akt, IL-17, and TNF
pathways related to psoriasis pathogenesis. Indirubin significantly affected the severity of
imiquimod-induced skin lesions in psoriasis-like mice. It also inhibited the expression of IL-6 and il-
1β inflammatory factors and rescued p65 and p-p65 expressions in psoriasis-like mice.

Conclusion:
Network pharmacology, combined with in vitro cellular experiments, tentatively confirmed
that Indirubin reduces the inflammatory response in psoriasis-like mice through the AHR/NF-
κB signaling pathway.
Ligustilide Inhibits the PI3K/AKT Signalling Pathway and Suppresses Cholangiocarcinoma Cell Proliferation, Migration, and Invasion
Authors: Wu Yue , Rong Li , Zhang Suifeng , He Yuxi , Song Na , Zuo Guoqing , Mei Zhechuan 
Published: August 2024

Background:
Angelica sinensis (Oliv.) Diels, a renowned traditional Chinese medicine,
has gained widespread recognition for its antitumor properties. Further investigation is
warranted to determine whether ligustilide (LIG), which is extracted from this plant, can effectively
inhibit tumors.

Objective:
We delved into the impact of LIG on cholangiocarcinoma cells, aiming to unravel
the mechanisms underlying its effects.

Materials and Methods:
Cholangiocarcinoma cells (HuccT1 and RBE) were exposed to varying
concentrations of LIG (2, 5, 10, 15, 20 μg/mL) for 24, 48, and 72 h. After identifying differentially
expressed genes, stable transcription strains were utilized to explore LIG’s antitumor
mechanism. The inhibitory effects of LIG (5 μg/mL, 48 h) were assessed by CCK-8, colony
formation, wound healing, transwell migration, western blotting, and immunofluorescence. In
vivo, experiments in NOG mice (Ac, Ac+LIG; five per group) evaluated LIG’s antiproliferative
efficacy (5 mg/kg, intraperitoneal injection, 18-day period).

Results:
LIG significantly inhibited cell proliferation and migration with IC50 5.08 and 5.77
μg/mL in HuccT1 and RBE cell lines at 48h, increased the expression of E-cadherin while decreased
N-cadherin and the protein of PI3K/AKT pathway. Silenced NDRG1 (N-Myc downstream-
regulated gene 1) attenuated these effects. In vivo, the AC+LIG group (LIG, 5 mg/kg,
qd, 18 d) exhibited smaller tumor volumes compared to the Ac group. The expression of Ki-67
was significantly downregulated in the AC+LIG group.

Conclusion:
For the first time, our study has revealed that LIG holds therapeutic potential for
treating cholangiocarcinoma. These findings hold promise for advancing innovative therapeutic
approaches in the treatment of cholangiocarcinoma. LIG may serve as a useful patent for treating
CCA.
Comprehensive Overview of Patents on Microstructure Surface Polishing Technology
Authors: Li Guo , Zhao Shupeng 
Published: August 2024

Background:
In recent years, there has been an increasing demand for metal microstructural
devices in fields such as biomedicine, aerospace, and precision machinery. The final step in the
processing of microcomponents is the polishing process, which aims to eliminate surface defects and
ensure stable mechanical performance of the structural components.

Objective:
By analyzing and discussing recent patents related to microstructure surface polishing,
valuable insights can be gained, and future research prospects can be provided.

Methods:
Through a comprehensive study of various patents concerning polishing techniques, this
paper aims to summarize the advancements made in microstructure surface polishing technology.

Results:
With the increasing demand for the application of microstructure devices, microstructure
polishing technology has become more and more important. Microstructure polishing technology can
effectively improve the quality of microstructure devices and ensure the high quality and efficiency
of the products.

Conclusion:
By elucidating the characteristics of polishing and emphasizing the significance of microstructure
surface polishing, it is concluded that ultra-precision polishing and nano-polishing represent
key directions for future development in this field.
Association of Single Nucleotide Polymorphism in OCT1 and OCT3 Genes with the Efficacy of Metformin Response in North Indian Type 2 Diabetes Mellitus Patients
Authors: Rizvi Saliha , Raza Syed Tasleem , Mahdi Farzana 
Published: August 2024

Introduction:
Variability in the effectiveness of metformin treatment among
individuals with type 2 diabetes mellitus (T2DM) has been linked to various genetic factors.
Understanding the genetic mechanisms underlying the action of metformin can
greatly aid the personalized management of T2DM. Our investigation aimed to explore
the impact of genetic variations in the organic cation transporters (OCT1 and OCT3)
genes on the efficacy of metformin therapy in T2DM individuals from North India.

Methods:
This observational cross-sectional study assessed the influence of OCT1
(rs628031) and OCT3 (rs2292334) polymorphisms on metformin response in T2DM patients.
Metformin response was determined based on HbA1c levels, dividing patients (n =
177) into two categories: responders (HbA1C<7%; n = 127) and non-responders
(HbA1C≥7%; n = 50). Responders were further classified as T2DM patients receiving either
monotherapy (n = 55) or combination therapy (n = 72). Genotyping was conducted
using the PCR-RFLP method.

Results:
No significant association was observed between OCT1 (rs628031) polymorphism
and metformin response in T2DM patients. However, a notable association was
found between OCT3 (rs2292334) polymorphism and metformin response. Carriers of the
AA genotype exhibited enhanced efficacy of metformin in both monotherapy (OR (CI)=
0.29(0.11-0.72), p=0.007) and combination therapy (OR (CI)= 0.41(0.16-1.0), p=0.047).
Additionally, the A allele was more prevalent in responders (OR (CI)= 0.48(0.28-0.84),
p=0.010), while the G allele was associated with reduced efficacy of metformin in T2DM
patients (OR (CI)= 2.07(1.19-3.61), p=0.010).

Conclusion:
Genotyping of OCT3 (rs2292334) may serve as a valuable tool in predicting
the response to metformin in T2DM patients.