bluuebunny/crossref_metadata_2025 huggingface dataset:
Peripheral Low Level Chronic LPS Injection as a Model of Neutrophil Activation in the Periphery and Brain in Mice
Authors: Aries Michelle , Cook Makayla , Hensley-McBain Tiffany
Published: October 2023

Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, peaked in the periphery after 4 weeks of weekly injections. Neutrophil frequency and activation increased in the periphery 4–12 hours and 4–8 hours after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 hours following the final injection. Neutrophils and neutrophil activation were increased in the brain of LPS injected mice when compared to saline-injected mice 4 hours and 4–8 hours after the final injection, respectively. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery-brain axis of inflammation with age and/or in mouse models of neurodegenerative or neuroinflammatory disease.
Salsal: Blockchain for Vetting Cultural Object Collections
Authors: Khelifi Adel , Altaweel Mark , Hashir Mohammad , Hadjitofi Tasoula , Ghazal Mohammad
Published: October 2023

Many modern cultural object collections suffer from the problem of being obtained in unethical and illegal circumstances. Additionally, information about collections, including their status, object descriptions, and other data need up-to-date information presented to users. We propose a novel blockchain tool called Salsal that enables the vetting of objects, individually or as part of more extensive collections, to meet required ethical and legal guidelines while informing users of relevant information about collections. Blockchain provides a better and more rapid way for users to know about collections using a decentralized and immutable ledger technology. We also believe that they can be used to incentivize or even pressure collections to vet their objects for ethical and legal guidelines that can benefit the public who use collections. The prototype software we have made is presented and compared to other blockchains, with code provided. We demonstrate how our blockchain can enable a useful vetting process for cultural objects, allowing a user community to contribute to this process in a transparent and secure manner.
Seismic Events in Central Kazakhstan by Data of The National Nuclear Center Monitoring Network of the Republic of Kazakhstan
Authors: Uzbekov Abylay , Mikhailova Natalya
Published: October 2023

Over the past ten years of observations by the seismic monitoring network of the National Nuclear Center of the Republic of Kazakhstan, seismic events of a different nature have been registered on the territory of central Kazakhstan. The largest number of these events are quarry explosions at deposits of solid minerals. But there are also tectonic earthquakes and natural-technogenic events induced by prolonged explosive activity in the field. Despite the fact that earthquakes are rarely recorded in such ‘weakly seismic’ areas, quite strong earthquakes can occur there, causing damage to the existing infrastructure near their sources. The paper presents materials on the study of the nature of seismic events and their interrelations with the deep structure of the environment, the tectonics of Central Kazakhstan and the distribution of anomalies of geophysical fields.
Assessment of Root Canal Morphology of Maxillary Premolars: A CBCT Study Exploring Age and Gender Variations
Authors: Karobari Mohmed Isaqali , Iqbal Azhar , Batul Rumesa , Adil Abdul Habeeb , Syed Jamaluddin , Algarani Hmoud Ali , Alonazi Meshal Aber , Noorani Tahir Yusuf
Published: October 2023

Background: In complex teeth like maxillary premolars, endodontic treatment success depends on a complete comprehension of root canal anatomy. While mandibular premolars have been extensively studied, there is little data on the root canal anatomy of maxillary premolars. This study aimed to explore the root canal morphology of maxillary premolars using cone-beam computed tomography (CBCT) imaging, considering age and gender variations.
Methods: From 500 patient CBCT scans, 1,230 maxillary premolar teeth were evaluated. The sample was divided by gender and age (10-20, 21-30, 31-40, 41-50, 51-60, and 61 years and older). Ahmed et al. classification system was used to record root canal morphology.
Results: The most frequent classifications for right maxillary 1st premolars were 2MPM1 B1 L1 (39.03%) and 1MPM1 (2.81%), while the most frequent classifications for right maxillary 2nd premolars were 2MPM1 B1 L1 (39.08%) and 1MPM1 (17.85%). Most of the premolars typically had two roots (left maxillary first premolars: 81.5%, left maxillary second premolars: 82.7%, right maxillary first premolars: 74.4%, right maxillary second premolars: 75.7%). Left and right maxillary 1st premolars for classes 1MPM1 and 1MPM1-2-1 showed significant gender differences. For classifications 1MPM1 and 1MPM1-2-1, age-related changes were seen in the left and right maxillary first premolars.
Conclusion: The research findings offer significant new knowledge of the complex and diverse root canal anatomy of maxillary premolars. The results highlight the significance of CBCT imaging for accurate treatment planning and clinical decision-making. Understanding the differences in root canal anatomy attributed to age and gender may facilitate endodontic treatment outcomes.
Immune dysregulation orchestrated by high-salt diet: Mechanistic insights into disease pathogenesis
Authors: Chen Li , chen Yixiao , Peng Xile , Chen Zhi-xuan , Tang Junrui , Wang Jie , nie Kaidi , QI Luming , Deng Tingting , Xia Li-na
Published: October 2023

Background Excessive salt consumption has been associated with detrimental health consequences, including hypertension, colitis, and autoimmune disorders. However, recent studies have proposed that high salt diet (HSD) can both stimulate the immune system, affecting the differentiation of immune cells, promoting or inhibiting cytokine secretion to fight cancer or elicit a more potent autoimmune response, and exerting an immunosuppressive effect to influence disease development, providing mechanistic insights into the direction of immune regulation in which HSD affects disease. Objective This paper reviews the immunomodulatory effects of HSD on various innate immune and adaptive cells, especially macrophages, dendritic cells, and T cells, in relation to disease development. Methods We identified papers by electronically searching the Web of Science (WOS) database from inception through March 2023. Results A growing number of animal experiments and in vitro cell culture studies have shown that HSD can regulate the differentiation and activation of a variety of immune cells, and promote or inhibit different cytokines to mediate the development of a variety of diseases, including nephropathy, hypertension, cancer, inflammatory bowel disease, and a number of autoimmune diseases. These findings provide a new mechanism for pathological changes in the direction of immune regulation and suggest that HSD is a predisposing factor for a variety of diseases, providing new mechanistic insights into dietary health modification. Conclusions HSD mediates the development of multiple diseases by regulating the differentiation and activation of a variety of immune cells, and the underlying mechanisms may be related to gut microbes and their metabolites.
Valorization of Cheese whey powder by two-step fermentation for gluconic acid and ethanol preparation
Authors: Zhang Rui , Li Fan , Liu Xinlu , Zhou Xin , Jiang Kankan
Published: October 2023

Whey from cheesemaking is an environmental contaminant with a high BOD, containing an abundance of lactose. Hence, it has the potential to be utilized in the manufacturing of bio-based chemicals that have increased worth. A designed sequential fermentation approach was employed in this research to convert enzymatic hydrolysate of cheese whey (which primarily consists of glucose and galactose) into gluconic acid and bio-ethanol. This conversion was achieved by utilizing Gluconobacter oxydans and Saccharomyces cerevisiae.Glucose in the enzyme hydrolysate will undergo preferential oxidation to gluconic acid as a result of the glucose effect from Gluconobacter oxydans. Subsequently, Saccharomyces cerevisiae will utilize the remaining galactose exclusively for ethanol fermentation, while the gluconic acid in the fermentation broth will be retained. As a result, approximately 293 g gluconic acid and 103 g ethanol could be produced from 1 kg of cheese whey powder. Simultaneously, it was feasible to collect a total of 140 g of blended protein, encompassing cheese whey protein and cellular protein. Two-step fermentation has proven to be an effective method for utilizing cheese whey in a sustainable manner and reducing the environmental impact.
MSFNET: A multi-level Semantic Fusion Network for Generative Machine Reading Comprehension
Authors: Li Qiang , Mo Cheng
Published: October 2023

The free question answering task in machine reading comprehension(MRC) is a challenge. Seq2Seq is a popular approach in this field, but traditional Seq2Seq only captures local semantics, which is far from enough for machine reading comprehension tasks. We propose a multi-level semantic fusion network, called MSFNET. MSFNET choose XLNET as embedding layer to get word-level semantics and processing sentence-level semantics by encoding sentences with multi-level bidirectional long short-term memory (Bi-LSTM) to get sentence-level, paragraph-level semantics and fuses different level semantics with attention mechanism. In output layer we propose an answer prediction method which combines seq2seq network with pointer network, and train it to determine whether the answer is generated by seq2seq or copied from the original text by the pointer network. Experiments on MS MARCO showed that MSFNET would be able obtain 32.75% ROUGE-L and 34.12% BLEU-4 scores, more effective than Match-LSTM and BIDAF.
Cerebral venous sinus thrombosis presenting as subarachnoid hemorrhage in a neuromyelitis optica spectrum disorder with positive anti-cardiolipin antibodies: a case report
Authors: ding yichen , wu jinxiu , he zhongxun , guo chai , wang weina , yu yunli
Published: October 2023

Background
Area postrema syndrome has a low prevalence of neuromyelitis optica spectrum disorder (NMOSD), and cerebral venous sinus thrombosis (CVST), which typically manifests as subarachnoid hemorrhage (SAH), is a less frequent complication.
Case presentation:
Here, we provide a case of a patient with recurrent NMOSD who had anti-cardiolipin antibodies that were positive and who experienced seizures while receiving plasma exchange (PE) and glucocorticoid shock therapy. The patient's condition was ultimately determined to be CVST with SAH as the manifestation after pertinent tests.
Conclusions
Taking the present case as an example, we analyzed the etiologies of thrombotic events during the treatment of CNS inflammatory diseases and found that the etiology is diverse and may be the result of a combination of causes. More clinical data is required to establish the precise process, although in addition to the basic itself, positive anti-cardiolipin antibodies, Glucocorticoids (GCs), and PE may cause the creation of this thrombotic event.
The Effects of Smokers Switching Behaviour on Health-Related Symptom Burden and Quality of Life: Analysis of US Prospective Longitudinal Cohort Study Data
Authors: Cao Yue , Zhang Xuxi , Fearon Ian , Li Jiaxuan , Chen Xi , Xiong Yuming , Zheng Fangzhen , Zhang Jianqiang , Sun Xinying , Liu Xiaona
Published: October 2023

Background
Ecigarette (EC) use is rising, and evidence increasingly supports that ECs are helpful in smoking cessation. However, evidence concerning the longterm health effects of conventional cigarette smokers who switch to using ECs, and changes in healthrelated symptoms and quality of life (QoL), are lacking.
Objective
To examine the effects of switching from smoking to using ECs on healthrelated symptoms (fatigue, pain, and emotional problems) and general QoL.
Methods
We analysed data from 7,122 adult respondents in the U.S. Population Assessment of Tobacco and Health (PATH) study. These were exclusive cigarette smokers at Wave 1 and were followed up at any of Waves 2 to 5. At the followup waves, respondents were categorised into four groups based on their switching behaviours: (1) full switching (switching to exclusive EC use); (2) partial switching (switching to dual use of cigarettes and ECs); (3) quitting (not beginning EC use); and (4) nonswitching (exclusive cigarette smoking). Linear mixedeffects models controlling for age, sex, race, level of education and time were used to calculate adjusted mean differences (aMD) with 95% confidence intervals (CI) in general QoL and related factors between nonswitching and switching groups.
Results
Compared to nonswitching, full switching was significantly associated with less fatigue (aMD − 0.092; CI -0.167 to -0.017; P = 0.016), less emotional problems (aMD − 0.089; CI -0.175 to -0.002; P = 0.044), better QoL (aMD − 0.124; CI -0.193 to -0.056; P < 0.001), but similar pain (aMD − 0.156; CI -0.351 to 0.038; P = 0.108). No significant differences were observed between partial switching and nonswitching groups for fatigue, pain, emotional problems, or QoL (P > 0.05 in all cases). Those who quitted smoking and did not begin EC use reported the lowest fatigue, pain, and emotional problems, and the best QoL, among the four groups (all P < 0.001).
Conclusions
Smokers who quitted smoking or fully switched to using ECs had less healthrelated symptoms and better QoL than those who continued smoking. This impact on QoL should be taken into account when assessing the harm reduction potential of ECs, and the development of practices to help smokers switch and improve their QoL also needs to be considered.
Design and Synthesis of N-terminal segment Peptides: A New Innovative Finding for Antimicrobial Activity
Authors: Krishnamoorthy Rajavenkatesh , Adhikari Priyanka , Anaikutti Parthiban , Rajagopal Saravanakumar ,   Rajendran Babhu Vignesh4
Published: October 2023

A novel short N-terminal cationic and hydrophobic peptides, KWKLFKKI-CONH2 (P2) and KWLWKKI-CONH2 (P3) are a class of Cecropin-A family of KWKLFKKIQIAK-CONH2 (P1) was designed using Fmoc-chemistry solid phase peptide synthesis protocol, where W stands for α-(2,5,7-tri-tert-butylindol-3-yl) alanine residue. By comparing High performance liquid chromatograms or Mass spectrometry (LCMS or analytical HPLC), the purity, integrity, and homogeneity of the peptide were determined. The circular dichroism spectroscopy (CD) demonstrates that to detect conformational alterations during membrane contact, P2 adopts an extended structure in both polar and non-polar settings, as expected. Because of the presence of tryptophan derivatives, P3 occurs in an extended conformation. Peptide P2 exhibited an exceptional affinity for both zwitterionic POPC lipid bilayer and anionic POPC/POPG lipid bilayer membranes, whereas P3 preferentially interacts with POPC/POPG anionic bilayer rather than zwitterionic POPC lipid bilayer. Surprisingly, both peptides have good antibacterial activity against Gram-positive and Gram-negative microorganisms. It is important to note that the most hydrophobic P3 had more effectiveness against all test organisms than P2 and the control peptide P1. The toxicity of these peptides was examined using a hemolytic assay, and the results reveal that P2 and P3 have very little to no toxicity, which is important for P2 and P3 to be utilised as possible therapeutic agents. Peptides P2 and P3 were both non-hemolytic and appeared to be more capable due to their broad antibacterial activity.
Psychiatric Disorders and Dietary Habits: An Investigation using Mendelian Randomization Analysis and Insights into Gene Expression Regulatory Mechanisms
Authors: Feng Yu , Shen Jing
Published: October 2023

Background
Dietary habits play a crucial role in life and may influence the development of psychiatric disorders (PD). Although observational studies have suggested an association between dietary habits and PD, establishing causality remains challenging due to confounding factors and study limitations.
Methods
In this study, we utilized dietary data from a vast cohort of over 500,000 participants recruited by the UK Biobank, along with genome-wide association study (GWAS) data for 11 PD. Leveraging two-sample Mendelian randomization (TSMR) and summary data-based Mendelian randomization (SMR) analyses, we integrated expression, methylation, and protein quantitative trait loci (eQTL, mQTL, and pQTL) data from brain tissue and blood.
Results
Our TSMR analyses revealed significant correlations between the intake of Cheese, Alcohol, and Dried fruit and multiple PD. SMR analyses identified several genes associated with these dietary habits, some of which were also linked to an increased risk of various PD. Furthermore, we observed a consistent association between the dietary habit-associated protein C1-Esterase Inhibitor and the risk of Insomnia, Major Depressive Disorder (MDD), and Neuroticism.
Conclusions
Our findings suggest a potential link between dietary habits and PD and shed light on plausible mechanisms underlying gene expression regulation. These results hold essential implications for future research on the pathogenesis of PD and the intricate relationship between diet and mental health. However, further investigations are warranted to validate and gain a deeper understanding of these associations, exploring additional contributing factors and elucidating the underlying mechanisms.
Comunicação científica e Ciência Aberta
Authors: de Mello Rode Sigmar , Penido Carmen
Published: October 2023

Comunicação científica e Ciência Aberta
Cumhuriyet Donanması’nın Oluşum ve Gelişim Süreci (1923-1938)
Authors: ATABEY Figen
Published: October 2023

Osmanlı Devleti’nden Türkiye Cumhuriyeti Devleti’ne devrolunan donanmanın neredeyse tamamı arızalı ve bakımsızdı. Donanmanın yapılandırılması için büyük gayretlere ihtiyaç vardı. Cumhurbaşkanı Mustafa Kemal Atatürk, Eylül 1924’te Hamidiye kruvazörü ile gerçekleştirdiği Karadeniz gezisinde Cumhuriyet Donanması’nın inşası için harekete geçileceğinin sinyalini verdi. Donanmayı güçlendirmeyi milli bir mesele olarak gören Atatürk’ün direktifleri doğrultusunda Bahriye Vekâleti’nin kurulması, Yavuz gemisinin onarımı, modern gemilerin donanma envanterine katılması, Gölcük’te bir deniz üssü inşası gibi atılımlar kademeli bir şekilde gerçekleştirildi. 20 Temmuz 1936’da Montreux Boğazlar Sözleşmesi’nin imzalanması ve Boğazların tekrar kayıtsız şartsız Türk hâkimiyetine girmesi Cumhuriyet Donanması’nın güçlenme sürecine büyük bir ivme kazandırdı. Cumhuriyet Donanması 1936 yılında gerçekleştirdiği Malta ve Yunanistan liman ziyaretleri ile Türkiye Cumhuriyeti’nin kısa sürede oluşturduğu deniz gücünü gururla tüm dünyaya gösterme fırsatını yakaladı. Çalışmanın amacı Cumhuriyet’in ilanı ile birlikte Türk askerî deniz gücünün yoktan var edilmesine giden on beş yıllık süreci incelemektir. Çalışmada bahse konu süreç, arşiv belgelerinin yansıra konuya ilişkin başvuru kaynaklarından ve dönemin gazete haberlerinden istifade edilerek, değerlendirildi.
Cumhuriyetin Kurucu Neslinden Bir Öğretmen Portresi Rifat Rami (Arıncı)
Authors: ARIKAN Mustafa
Published: October 2023

Türkiye Cumhuriyeti, Osmanlı Devleti’nin son yüzyılı şartlarının ve özellikle on yıllık savaş sürecinin ortaya çıkardığı bir neticedir. On dokuzuncu yüzyılın son yıllarında doğanlar bu tarihin şahidi ve bazıları kahramanları olmuşlardır. Rifat Rami (Arıncı) bu nesilden bir şahsiyettir. Birinci Dünya Savaşı sebebiyle tahsili yarım kalmış, esaret hayatı yaşamış, Mütarekeden sonra memleketi Çorum/İskilip’te Millî Mücadele’ye hizmet etmiştir. Sakarya Savaşı’nın hemen sonrasında o bir öğretmendir. Cumhuriyetin ilanından sonra ihtiyaç olan yeni nesilleri yetiştirmek ve vatandaş kimliği oluşturmak için sadece mektep ortamında değil; Türk Ocağı ve Halkevleri gibi kurumların çatısı altında faaliyetlerde bulunmuştur. Yayımlanmasında büyük emeğinin olduğu Kurtuluş Yolu adlı dergide eğitim/öğretime dair yazılar kaleme almış, şiirler yazmıştır. Cehalet ve taassupla mücadele etmiş, öğretimde birliği savunmuş, mektep ve kütüphanenin önemine dikkat çekmiştir. Halkevindeki faaliyetleri ile bölgenin tarihine, dil ve edebiyatına katkı sağlamıştır. Erken Cumhuriyet yıllarında, halkın içinden birisi, bir aydın ve bir öğretmen olarak omuzlarına yüklenmiş vazifeyi idrak etmiş ve yerine getirmeye çalışmıştır. Bu araştırmanın ortaya çıkmasına, kendisinin oluşturduğu ve ailesinin muhafaza ettiği belge, yazı ve fotoğraflar da özgün bir katkı sağlamıştır.
The research on the legal nature of Project Implementation Plan and its Authorization on ACT ON THE IMPROVEMENT OF URBAN AREAS AND RESIDENTIAL ENVIRONMENTS: Focusing on the case where the project implementer is a cooperative
Authors:   European Constitutional Law Association, Kim Minsub
Published: October 2023

Regarding the legal nature of the project implementation plan and its authorization, There are conflicting opinions. They are ① the view that the project implementation plan is a disposition and the approval is regarded as a academic approval, ② the view that the project implementation plan's general meeting resolution is a judicial act and its approval is a academic approval ③ the view of viewing the project implementation plan as an act of establishing authority, ④ the view of viewing the project implementation plan as an administrative plan, and the view of viewing the approval as an act of finalizing the plan. Judicial precedents regard the project implementation plan as a disposition, and its approval as academic approval.
Since it seems difficult to deny the administrative subjectivity of a cooperative, it is reasonable to view the project implementation plan as an administrative disposition taken by the administrative agency after the cooperative has obtained the status of an administrative subject through its establishment authorization disposition, and its approval as a lecturer's approval. do. Then, as seen above, there may be a problem that the project implementation plan before approval as an administrative disposition overlaps with the approval as a disposition.
Recognizing the dual nature of the association, it would be reasonable to view the project implementation plan as an administrative disposition carried out by the association as the subject of intrusive administration, and whether the project implementation plan was approved would reflect the effectiveness of the legal acts that the association performed as an object of beneficial administration. It is reasonable to regard it as a profitable disposition by the administrative agency for the request for completion.
Effects of anticipatory humanitarian cash assistance to households forecasted to experience extreme flooding: evidence from Bangladesh
Authors: Gros Clemens , Pronti Andrea , Sheikh Khairul , Hassan Ahmadul , Shahjahan Mohammad
Published: October 2023

The 2020 monsoon floods in Bangladesh were among the most severe and protracted in decades. Instead of waiting for disaster to strike, the Bangladesh Red Crescent Society used impact-based forecast data to reach nearly 3,800 vulnerable households along the Jamuna River with a one-off unconditional cash transfer of BDT 4,500 (about $53) before peak flooding in July 2020. Anticipatory action to help at-risk populations avoid or mitigate extreme weather event impacts has become widely used by governments and humanitarian organisations worldwide. However, robust evaluations of the effectiveness of forecast-based assistance are limited. This assessment follows a quasi-experimental approach, drawing on survey data from a sample of cash recipients and equally vulnerable and flood-affected households that were not reached by BDRCS before the flood. Our analysis finds robust statistical evidence that the intervention was effective in helping households evacuate the flood-affected area, protecting personal health and well-being, and safeguarding people's productive assets and livestock. It was also effective in enabling beneficiaries to avoid taking on high-interest loans and selling valuable assets during and after the flood. The intervention does not appear to have helped cash recipients avoid food-based coping mechanisms or regain their productive capacity sooner after the flood.
Heroínas Negras
Authors: Almeida da Hora Silva Rayza , Oliveira de Carvalho Moura Tatiane
Published: October 2023

Em 2023, a Lei 10.639, que torna obrigatório o ensino de História e Cultura Afro-brasileira e Africana, completa vinte anos de existência. Nesse sentido, neste artigo apresenta-se uma possibilidade de mediação didática para o ensino de Sociologia no Ensino Médio. Tal mediação foi pensada a partir da obra de Arraes, "Heroínas Negras Brasileiras" (Arraes, 2020), mesclando elementos da literatura cordelista com saberes sociológicos, visando pavimentar o caminho para uma Sociologia antirracista. É importante ressaltar que este projeto ainda não foi aplicado em sala de aula, mas foi concebido levando em consideração a nova realidade do docente em Sociologia. Dessa forma, o trabalho articula saberes, utilizando o cordel como uma ferramenta em sala de aula, estimulando a ludicidade e a imaginação sociológica (Mills, 1982) do estudante.
Beyond the Dusty Fog: Local Eye Drop Therapy and Potentially New
Treatment Alternatives in Pseudoexfoliative Glaucoma
Authors: Zeppieri Marco , Musa Mutali
Published: October 2023

Pseudoexfoliative glaucoma (PEG) is a type of secondary open-angle glaucoma
characterized by the accumulation of whitish-gray material on the trabecular meshwork
and lens, leading to an increase in intraocular pressure (IOP) and optic nerve damage. Local
eye drop therapy is one of the first-line treatments for PEG, which include prostaglandin
analogues, beta-blockers, and alpha-adrenergic agonists to lower IOP. New treatments
beyond conventional techniques, however, are constantly being developed. One potential
treatment proposed for PEG is based on magnetic phage display, which involves using
magnetic nanoparticles conjugated to specific peptides or proteins selected using phage
display techniques to remove aggregates in the anterior chamber of the eye or inflammatory
cells and cytokines that contribute to PEG pathogenesis. Other potential treatments include
microRNAs (miRNAs) that are involved in the regulation of gene expression at the
post-transcription stages. Gene therapies, nanotechnology, immunotherapy and methods
based on stem cells can also be potentially used to target and treat specific tissues and
cells responsible for regulating IOP. In addition, photobiomodulation therapy (PBMT), a
non-invasive procedure that utilizes low-level laser therapy to improve cellular function
and promote tissue repair, can prove an interesting alternative in treating PEG. The aim of
our mini-review is to provide a brief overview of these innovative methods that appear to
offer potentially promising treatment options for PEG.
The Potential Role of Cardiokines in Heart and Kidney Diseases
Authors: Yang Ming , Luo Shilu , Yang Jinfei , Chen Wei , He Liyu , Liu Di , Wang Xi , Sun Lin
Published: October 2023

As the engine that maintains blood circulation, the heart is also an endocrine
organ that regulates the function of distant target organs by secreting a series of cardiokines.
As endocrine factors, cardiokines play an indispensable role in maintaining the
homeostasis of the heart and other organs. Here, we summarize some of the cardiokines
that have been defined thus far and explore their roles in heart and kidney diseases. Finally,
we propose that cardiokines may be a potential therapeutic target for kidney diseases.
ROS-mediated Therapeutics Combined with Metal-based Porphyrin Nanoparticles and their Applications in Tumor Treatment
Authors: Yang Lingyan , Shi Lei , Liu Yihui , Liu Zhenhua , Tian Zejie , Li Hui , Zhang Jiayao , He Jun , Liu Yunmei
Published: October 2023

High concentrations of reactive oxygen species (ROS) can disrupt cell structure
and induce apoptosis and necrosis of tumor cells. Photodynamic therapy (PDT) and
chemodynamic therapy (CDT) are two cancer treatments mediated by reactive oxygen
species. Oxygen molecules (O2) are one of the indispensable factors in PDT and hypoxic
tumor sites limit its application. However, another ROS-mediated method, CDT, can
generate •OH and O2in situ by Fenton reaction or Fenton-like reaction. Synergistic
PDT/CDT therapy is a strategy to overcome the limitations of tumor microenvironment
therapy. In this review, PDT and CDT therapies are briefly introduced, with an emphasis
on metal-basrd porphyrin nanoparticles constructed in different ways for PDT/CDT
dual-mode therapy. By introducing the history and latest design schemes of the treatment
model, it provides ideas for researchers engaged in ROS-mediated cancer therapies.
Remarkable Effects of a Rhenium(I)-diselenoether Drug on the Production of
Cathepsins B and S by Macrophages and their Polarizations
Authors: Collery Philippe , Desmaële Didier , Harikrishnan Adhikesavan , Veena Vijay
Published: October 2023

Background/Objective:

Tumor-associated macrophages (TAMs) produce an excessive amount of
cysteine proteases, and we aimed to study the effects of anticancer rhenium(I)-diselenoether (Re-diSe) on the
production of cathepsins B and S by macrophages. We investigated the effect of Re-diSe on lipopolysaccharides
(LPS) induced M1 macrophages, or by interleukin 6 (IL-6) induced M2 macrophages.

Methods:

Non-stimulated or prestimulated murine Raw 264 or human THP-1 macrophages were exposed to
increasing concentrations of the drug (5, 10, 20, 50 and 100 μM) and viability was assayed by the MTT assay.
The amount of cysteine proteases was evaluated by ELISA tests, the number of M1 and M2 macrophages by
the expression of CD80 or CD206 biomarkers. The binding of Re-diSe with GSH as a model thiol-containing
protein was studied by mass spectrometry.

Results:

A dose-dependent decrease in cathepsins B and S was observed in M1 macrophages. There was no
effect in non-stimulated cells. The drug induced a dramatic dose-dependent increase in M1 expression in both
cells, significantly decreased the M2 expression in Raw 264 and had no effect in non-stimulated macrophages.
The binding of the Re atom with the thiols was clearly demonstrated.

Conclusion:

The increase in the number of M1 and a decrease in M2 macrophages treated by Re-diSe could
be related to the decrease in cysteine proteases upon binding of their thiol residues with the Re atom.
Ras-related Protein in Brain 4A (Rab4A) is Downregulated by miR-496 to inhibit the Progression of Gastric Cancer
Authors: Su Rui , Su Meng , Lu Yan
Published: October 2023

Introduction:

Ras-related protein in brain 4A (Rab4A), as a member of the Rab family,
is involved in the intracellular circulation of membrane receptors or endocytic substances and
regulates the progression of multiple tumors.

Methods:

From our results, the knockdown of Rab4A inhibited the proliferation, migration and invasion
in AGS cells. Importantly, the surface expression of epidermal growth factor receptor (EGFR)
declined significantly in Rab4A knockdown cells. The downstream pathway of EGFR was also inhibited
after the transfection of Rab4A-specific siRNA, including AKT and β-catenin pathways.

Result:

In addition, miR-496 down-regulated the expression of Rab4A in AGS cells. The result
of the luciferase reporter assay showed that miR-496 could bind to the 3’UTR of Rab4A.

Conclusion:

In conclusion, the expression of Rab4A is inhibited by miR-496, and the knockdown
of Rab4A inhibits the proliferation, migration and invasion through down-regulating the
surface expression of EGFR. Rab4A is a potential target in the treatment of gastric cancer.
Phytochemistry and Pharmacological Activity of Malva sylvestris L:
A Detailed Insight
Authors: Paul Zahid Ahmad , Malla Aamir Tariq , Dar Mohammad Akbar , Masoodi Mubashir Hussain
Published: October 2023

:

Malva sylvestris L., is commonly referred to as Mallow and is found in Europe, Asia
and Africa. This has been traditionally used for inflammation, gastrointestinal disturbances, skin
disorders, menstrual pains, and urological disorders. This review covers phytoconstituents and
Pharmacological activities of M. sylvestris. The plant contains a large number of phytochemical
constituents having diverse pharmacological activities. The plant contains many phenolic compounds
responsible for its strong antioxidant activity. Coumarins from Mallow have a potential
anticancer activity. Malva sylvestris also contains essential as well as non-essential elements and
minerals. Many researchers have provided evidence that Malva sylvestris is a good candidate for
use as a medicinal herb and has good nutritional value. The leaves, in particular, offer properties
like anticancer, skin whitening, and anti-aging. Furthermore, the aqueous extract was recently
shown to have an anti-ulcerogenic effect. Malva sylvestris has a high potential for use in cosmetics
such as skin whitening and anti-aging treatments. Methanolic extracts of Malva sylvestris
leaves, and flowers showed strong antibacterial activity against a common plant pathogen bacterium.
The plant also contains Malvone A, which is responsible for antibacterial action. The plant
also possesses anti-inflammatory, analgesic, wound healing properties and various other activities.
Network-Pharmacology-Based Study on Active Phytochemicals and Molecular Mechanism of Cnidii Fructus in Treating Colorectal Cancer
Authors: Wei Zhihui , Zhang Xiaoyun , Peng Antang , Liu Chenxu , Pang Jianying , Zhang Yajing , Duan Xuhong
Published: October 2023

Aims:

Cnidii Fructus (CF) is known for its antibacterial, anti-inflammatory, and antitumor
properties, as well as its activities against kidney deficiency and impotence. In this study,
we aimed to explore the anti-CRC cancer effect and molecular mechanism of CF via network
pharmacology and in vitro antitumor experiments.

Methods:

Network pharmacology was used to investigate the anti-CRC mechanism of CF. First,
a series of databases was used to screen the active phytochemical targets and anti-CRC core targets.
Then, the GO and KEGG pathways were analyzed to predict possible mechanisms. Molecular
docking analysis explore core targets-phytochemicals interactions. In vitro antitumor experiments
were carried on verifying anti-CRC mechanism of CF.

Results:

In this study, 20 active ingredient targets and 50 intersecting targets were analyzed by
Cytoscape software 3.9.1 to obtain the core genes and phytochemicals. Then, the GO and KEGG
pathways of 50 intersecting targets were analyzed to predict possible mechanisms. The results
from GO and KEGG indicated that CF has significant antitumor efficacy, which involves many
signaling pathways, such as PI3K/AKT and p53. The five core targets and five core phytochemicals
were screened for molecular docking to show protein-ligand interactions. According to the
results of molecular docking, the compound O-acetylcolumbianetin was selected for the anti-
CRC functional verification in vitro. MTT assay showed that O-acetylcolumbianetin significantly
inhibited the proliferation of colorectal HCT116 cells in a time- and quantity-dependent manner.
O-acetylcolumbianetin can promote the expression of CASP3 protein, induce HCT116 cells
apoptosis, thus exert anti-CRC effect.

Conclusion:

This study preliminarily verified the anti-CRC effect and molecular mechanism of
CF and provided a reference for Traditional Chinese Medicine anti-tumor subsequent research.
BAO-Ag-NPs as Promising Suppressor of ET-1/ICAM-1/VCAM-1
Signaling Pathway in ISO-induced AMI in Rats
Authors: Mosaad Yasser O. , Ateyya Hayam , Hussein Mohammed A. , Moro Ahmed M. , Abdel-Wahab Ebtsam A. , El-Ella Amr A. , Nassar Zahraa N.
Published: October 2023

Objectives:

Acute myocardial infarction (AMI) is the most prevalent cause of myocardial
fibrosis and the leading cause of mortality from cardiovascular disease. The goal of this
work was to synthesize Balanites aegyptiaca oil-silver nanoparticles (BAO-Ag-NPs) and evaluate
their cardioprotective effect against ISO-induced myocardial infarction in rats, as well as
their mechanism.

Materials and Methods:

BAO was isolated, and the unsaturated fatty acids were estimated.
BAO-Ag-NPs was prepared, LD50 was calculated to evaluate its cardioprotective activity
against ISO (85 mg/kg)-induced AMI. Different doses of BAO-Ag-NPs (1/50 LD50; 46.6
mg/kg.b.w and 1/20 LD50; 116.5 mg) were received to the rats.

Results:

The total fatty acids and unsaturated fatty acids generated by BAO were 909.63 and
653.47 mg/100 g oil, respectively. Oleic acid methyl ester, 9-octadecenoic acid methyl ester, and
9, 12-Octadecadienoic acid methyl ester were the predominant ingredients, with concentrations
of 107.6, 243.42, and 256.77 mg/100 g oil, respectively. According to TEM and DLS examinations,
BAO-Ag-NPs have a size of 38.20 ± 2.5 nm and a negative zeta potential of -19.82 ± 0.30
mV, respectively. The LD50 of synthesized BAO-Ag-NPs is 2330 mg. On the other hand, BAOAg-
NPs reduce myocardial necrosis by lowering increased BNP, cTnI, CK-MB, TC, TG, MDA,
MMP2, TGF-β1, PGE2, and IL-6 levels. Furthermore, BAO-Ag-NPs inhibit the expression of
ET-1, ICAM-1, and VCAM-1 genes as well as enhance HDL-C, CAT, and GSH levels when
compared to the ISO-treated group of rats. Histopathological findings suggested that BAO-Ag-
NPs enhance cardiac function by increasing posterior wall thickness in heart tissues.

Conclusion:

BAO-Ag-NPs protect against AMI in vivo by regulating inflammation, excessive
autophagy, and oxidative stress, as well as lowering apoptosis via suppression of the ET-1,
ICAM-1, and VCAM-1 signaling pathways.
Research Progress of Eucommia ulmoides Oliv and Predictive Analysis of
Quality Markers Based on Network Pharmacology
Authors: Zhao Xiaomei , Qu Qiong , Zhang Ying , Zhao Peiyuan , Qiu Jinqing , Zhang Xinbo , Duan Xi , Song Xiao
Published: October 2023

Du Zhong is a valuable Chinese medicinal herb unique to China. It is a national second-
class precious protected tree, known as “plant gold”, which has been used to treat various
diseases since ancient times. The main active ingredients are lignans, phenylprophetons, flavonoids,
iridoids and steroids and terpenoids, which have pharmacological effects such as lowering
blood pressure, enhancing immunity, regulating bone metabolism, protecting nerve cells, protecting
liver and gallbladder and regulating blood lipids. In this paper, a comprehensive review
of Eucommia ulmoides Oliv. was summarized from the processing and its compositional changes,
applications, chemical components, pharmacological effects, and pharmacokinetics, and the
Q-marker of Eucommia ulmoides Oliv. is preliminarily predicted from the aspects of traditional
efficacy, medicinal properties and measurability of chemical composition, and the pharmacodynamic
substance basis and potential Q-marker of Eucommia ulmoides Oliv. are further analyzed
through network pharmacology. It is speculated that quercetin, kaempferol, β-sitosterol, chlorogenic
acid and pinoresinol diglucoside components are selected as quality markers of Eucommia
ulmoides Oliv., which provide a basis for the quality control evaluation and follow-up research
and development of Eucommia ulmoides Oliv.
Viaminate Inhibits Propionibacterium Acnes-induced Abnormal Proliferation
and Keratinization of HaCat Cells by Regulating the S100A8/S100A9-
MAPK Cascade
Authors: Cao Junjie , Xu Meifeng , Zhu Longfei , Xiao Shengxiang
Published: October 2023

Background:

Viaminate, a vitamin A acid drug developed in China, has been clinically
used in acne treatment to regulate epithelial cell differentiation and proliferation, inhibit keratinization,
reduce sebum secretion, and control immunological and anti-inflammatory actions; however,
the exact method by which it works is unknown.

Methods:

In the present study, acne was induced in the ears of rats using Propionibacterium acnes
combined with sebum application

Results:

After 30 days of treatment with viaminate, the symptoms of epidermal thickening and keratin
overproduction in the ears of rats were significantly improved. Transcriptomic analysis of rat
skin tissues suggested that viaminate significantly regulated the biological pathways of cellular
keratinization. Gene differential analysis revealed that the S100A8 and S100A9 genes were significantly
downregulated after viaminate treatment. The results of qPCR and Western blotting confirmed
that viaminate inhibited the expression of S100A8 and S100A9 genes and proteins in rat
and HaCat cell acne models, while its downstream pathway MAPK (MAPK p38/JNK/ERK1/2)
protein expression levels were suppressed. Additional administration of the S100A8 and S100A9
complex protein significantly reversed the inhibitory effect of viaminate on abnormal proliferation
and keratinization levels in acne cell models.

Conclusion:

In summary, viaminate can improve acne by modulating S100A8 and S100A9 to inhibit
MAPK pathway activation and inhibit keratinocyte proliferation and keratinization levels.
Vegetable Mountain Products, as Functional Food. A Cross-sectional
Study of European Romanian Agricultural Producers
Authors: Covaci Brindusa , Brejea Radu Petru , Covaci Mihai
Published: October 2023

Background::

Mountain areas, in a normal ecosystemic context as the analyzed region
from the European Romanian Carpathians, offer healthier solutions through different agronomical
practices and solutions designed for the production of functional food. The paper approaches a
chain formed by mountain functional food – agronomic practices – mountain products commerce,
the purpose being the development of the entire mountain products value chain from an area focusing on the matrix "from the farm to the fork". The paper analyzes highly consumed mountain products with functional food roles Allium cepa, Allium sativum, Cucumis sativus, Capsicum, and
Solanum lycopersicum.

Objective:

The research highlights the importance of vegetable mountain products as a functional
food in the current hunger and environment contexts, in a more and more polluted world

Methods::

The experimental, clinical, and agronomical research, together with the production territorial profile, show that mountain products present high qualitative valences comparatively with
low-land areas or with reference values given by USDA.

Results::

According to macro-nutritional and micro-nutritional analysis – lipids-fats, saturated fatty acids, protein, cyanocobalamin (B12), ergocalciferol (D2
), cholecalciferol (D3
), iron and calcium
– Allium sativum dominates the mountain product's top with a functional food role. Instead of this,
mountain producers prefer to cultivate mountain products with a higher income horizon.

Conclusion::

Functional food represents an imperative in a more polluted world. Being less polluted than other ecosystems, the mountain area offers healthier agricultural products and requires
notable investments, together with more involved agronomy.
Applications of PET and SPECT in Patients with Autism Spectrum Disorder
Authors: Martini Anna Lisa , Quartuccio Natale , Schiera Irene Giovanna , Berti Valentina , Burroni Luca , Cistaro Angelina
Published: October 2023

Autism spectrum disorder (ASD) consists of neurological development disorders that manifest before three years of age and affect social
interactions, markedly restricting range of interests and activities, often associated with some degree of intellectual disability. Single-photon
emission computed tomography (SPECT) and positron emission tomography (PET) are non-invasive imaging tools to investigate the function of
the brain in vivo. SPECT and PET studies exploring rCBF and brain glucose metabolism in patients with ASD have been performed, providing
important insights into the brain regions involved in ASD. Abnormalities in serotonergic, dopaminergic, GABAergic, cholinergic, and
glutamatergic systems have been suggested to contribute to the observed distorted brain circuitry associated with ASD. However, the specificity of
such abnormalities needs to be fully clarified because schizophrenia and other psychiatric diseases have been shown to present with comparable
changes in neurotransmitter systems. Neuroinflammation could also play a role in the development of autism. Therefore, ASD is a complicated
process involving a number of factors. It is mandatory to perform more research studies to determine the molecular cornerstone of ASD and to
improve our comprehension of the clinical correlates of ASD.
An Awareness of Pharmacovigilance Among Healthcare Professionals Due
to an Underreporting of Adverse Drug Reactions Issue: A Systematic
Review of the Current State, Obstacles, and Strategy
Authors: Putri Risani Andalasia , Ikawati Zullies , Rahmawati Fita , Yasin Nanang Munif
Published: October 2023

Background:

Healthcare professionals play an essential role in reporting adverse
drug reactions as part of pharmacovigilance activities. However, adverse drug reactions reported
by healthcare professionals remain low.

Objective:

The aim of this systematic review was to investigate healthcare professionals'
knowledge, awareness, attitude, and practice on pharmacovigilance and adverse drug reaction
reporting, explore the causes of the underreporting issue, and provide improvement strategies.

Methods:

This systematic review was conducted using four electronic databases for original papers,
including PubMed, Scopus, Google Scholar, and Scholar ID. Recent publications from 1st January
2012 to 31st December 2022 were selected. The following terms were used in the search: "awareness",
"knowledge", "adverse drug reaction", "pharmacovigilance", "healthcare professional", and "underreporting
factor". Articles were chosen, extracted, and reviewed by the two authors.

Results:

Twenty-five studies were selected for systematic review. This review found that
24.8%–73.33% of healthcare professionals were unaware of the National Pharmacovigilance
Center. Around 20%–95.7% of healthcare professionals have a positive attitude toward
pharmacovigilance and adverse drug reaction reporting, while 12%–60.8% of healthcare
professionals have experience reporting any adverse drug reaction in their practice. The most
frequently highlighted barriers to pharmacovigilance were a lack of awareness and knowledge
regarding what, when, and to whom to report.

Conclusion:

Underreporting issues require immediate attention among healthcare professionals
due to a lack of awareness and knowledge of pharmacovigilance and adverse drug reaction
reporting. Educational and training program interventions have been suggested by most studies
to address these issues.