bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin D Status and Psoriatic Arthritis: Association with the Risk for Sacroiliitis and Influence on the Retention Rate of Methotrexate Monotherapy and First Biological Drug Survival—A Retrospective Study
Authors: Rotondo Cinzia , Cantatore Francesco Paolo , Cici Daniela , Erroi Francesca , Sciacca Stefania , Rella Valeria , Corrado Addolorata
Published: March 2023

A growing body of evidence on the importance of vitamin D in immune modulation has increased the interest in its possible impact on the course of rheumatological diseases. The scope of our study is to assess if the presence of different statuses of vitamin D could interfere in the clinical subsets, in methotrexate monotherapy discontinuation, and biological drug (b-DMARDs) survival in psoriatic arthritis patients (PsA). We conducted a retrospective study on PsA patients and split them into three groups based on their vitamin D status: the group with 25(OH)D ≤ 20 ng/mL, the group with levels of 25(OH)D between 20 and 30 ng/mL, and the group with serum levels of 25(OH)D ≥ 30 ng/mL. All patients were required to fulfill the CASPAR criteria for psoriatic arthritis and to have the evaluation of vitamin D serum levels at baseline visit and at clinical follow-up visits. The exclusion criteria were ages less than 18 years old, the presence of HLA B27, and satisfaction of rheumatoid arthritis classification criteria (during the study time). Statistical significance was set at p ≤ 0.05. Furthermore, 570 patients with PsA were screened and 233 were recruited. A level of 25(OH)D ≤ 20 ng/mL was present in 39% of patients; levels of 25(OH)D between 20 and 30 ng/mL presented in 25% of patients; 65% of patients with sacroiliitis presented 25 (OH)D ≤ 20 ng/mL. Methotrexate monotherapy discontinuation for failure was higher in the group with 25 (OH)D ≤ 20 ng/mL (survival time: 92 ± 10.3 weeks vs. 141.9 ± 24.1 weeks vs. 160.1 ± 23.6 weeks; p = 0.02) with higher discontinuation risk (HR = 2.168, 95% CI 1.334, 3.522; p = 0.002) than those with 25(OH)D between 20 and 30 ng/mL and those with 25(OH)D ≥ 30 ng/mL. Significantly shorter survival of first b-DMARDs was assessed in the group with 25 (OH)D ≤ 20 ng/mL versus the other groups (133.6 ± 11 weeks vs. 204.8 ± 35.8 weeks vs. 298.9 ± 35.4; p = 0.028) (discontinuation risk 2.129, 95% CI 1.186, 3.821; p = 0.011). This study highlights significant differences in clinical presentation, in particular sacroiliac involvement and on drug survival (methotrexate and b-DMARDs) in PsA patients with vitamin D deficiency. Further prospective studies, including a larger sample of patients, are needed to validate these data and to assess if the supplementation of vitamin D could improve the b-DMARDs response in PsA patients.
Potential Role of Fenestrated Septa in Axonal Transport of Golgi Cisternae and Gap Junction Formation/Function
Authors: Peracchia Camillo
Published: March 2023

Crayfish axons contain a system of parallel membranous cisternae spaced by ~2 μm and oriented perpendicularly to the axon’s long axis. Each cisterna is composed of two roughly parallel membranes, separated by a 150–400 Å wide space. The cisternae are interrupted by 500–600 Å pores, each occupied by a microtubule. Significantly, filaments, likely made of kinesin, often bridge the gap between the microtubule and the edge of the pore. Neighboring cisternae are linked by longitudinal membranous tubules. In small axons, the cisternae seem to be continuous across the axon, while in large axons they are intact only at the axon’s periphery. Due to the presence of pores, we have named these structures “Fenestrated Septa” (FS). Similar structures are also present in vertebrates, including mammals, proving that they are widely expressed in the animal kingdom. We propose that FS are components of the “anterograde transport” mechanism that moves cisternae of the Golgi apparatus (GA) toward the nerve ending by means of motor proteins, likely to be kinesins. In crayfish lateral giant axons, we believe that vesicles that bud off FS at the nerve ending contain gap junction hemichannels (innexons) for gap junction channel and hemichannel formation and function.
Haslea ostrearia Pigment Marennine Affects Key Actors of Neuroinflammation and Decreases Cell Migration in Murine Neuroglial Cell Model
Authors: Méresse Sarah , Gateau Hélène , Tirnan Tessa , Larrigaldie Vanessa , Casse Nathalie , Pasetto Pamela , Mouget Jean-Luc , Mortaud Stéphane , Fodil Mostefa
Published: March 2023

Haslea ostrearia, a cosmopolitan marine pennate diatom, produces a characteristic blue pigment called marennine that causes the greening of filter-feeding organisms, such as oysters. Previous studies evidenced various biological activities of purified marennine extract, such as antibacterial, antioxidant and antiproliferative effects. These effects could be beneficial to human health. However, the specific biological activity of marennine remains to be characterized, especially regarding primary cultures of mammals. In the present study, we aimed to determine in vitro the effects of a purified extract of marennine on neuroinflammatory and cell migratory processes. These effects were assessed at non-cytotoxic concentrations of 10 and 50μg/mL on primary cultures of neuroglial cells. Marennine strongly interacts with neuroinflammatory processes in the immunocompetent cells of the central nervous system, represented by astrocytes and microglial cells. An anti-migratory activity based on a neurospheres migration assay has also been observed. These results encourage further study of Haslea blue pigment effects, particularly the identification of molecular and cellular targets affected by marennine, and strengthen previous studies suggesting that marennine has bioactivities which could be beneficial for human health applications.
Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells
Authors: Sundqvist Martin O. , Wärme Jonatan , Hofmann Robin , Pawelzik Sven-Christian , Bäck Magnus
Published: March 2023

Helicobacter pylori (H. pylori) has been associated with cardiovascular diseases. The pro-inflammatory H. pylori virulence factor cytotoxin-associated gene A (CagA) has been detected in serum exosomes of H. pylori-infected subjects and may exert systemic effects throughout the cardiovascular system. The role of H. pylori and CagA in vascular calcification was hitherto unknown. The aim of this study was to determine the vascular effects of CagA through human coronary artery smooth muscle cell (CASMC) osteogenic and pro-inflammatory effector gene expression as well as interleukin 1β secretion and cellular calcification. CagA upregulated bone morphogenic protein 2 (BMP-2) associated with an osteogenic CASMC phenotype switch and induced increased cellular calcification. Furthermore, a pro-inflammatory response was observed. These results support that H. pylori may contribute to vascular calcification through CagA rendering CASMCs osteogenic and inducing calcification.
A Cinnamate 4-HYDROXYLASE1 from Safflower Promotes Flavonoids Accumulation and Stimulates Antioxidant Defense System in Arabidopsis
Authors: Hou Yuying , Wang Yufei , Liu Xiaoyu , Ahmad Naveed , Wang Nan , Jin Libo , Yao Na , Liu Xiuming
Published: March 2023

C4H (cinnamate 4-hydroxylase) is a pivotal gene in the phenylpropanoid pathway, which is involved in the regulation of flavonoids and lignin biosynthesis of plants. However, the molecular mechanism of C4H-induced antioxidant activity in safflower still remains to be elucidated. In this study, a CtC4H1 gene was identified from safflower with combined analysis of transcriptome and functional characterization, regulating flavonoid biosynthesis and antioxidant defense system under drought stress in Arabidopsis. The expression level of CtC4H1 was shown to be differentially regulated in response to abiotic stresses; however, a significant increase was observed under drought exposure. The interaction between CtC4H1 and CtPAL1 was detected using a yeast two-hybrid assay and then verified using a bimolecular fluorescence complementation (BiFC) analysis. Phenotypic and statistical analysis of CtC4H1 overexpressed Arabidopsis demonstrated slightly wider leaves, long and early stem development as well as an increased level of total metabolite and anthocyanin contents. These findings imply that CtC4H1 may regulate plant development and defense systems in transgenic plants via specialized metabolism. Furthermore, transgenic Arabidopsis lines overexpressing CtC4H1 exhibited increased antioxidant activity as confirmed using a visible phenotype and different physiological indicators. In addition, the low accumulation of reactive oxygen species (ROS) in transgenic Arabidopsis exposed to drought conditions has confirmed the reduction of oxidative damage by stimulating the antioxidant defensive system, resulting in osmotic balance. Together, these findings have provided crucial insights into the functional role of CtC4H1 in regulating flavonoid biosynthesis and antioxidant defense system in safflower.
Rhamnolipid Self-Aggregation in Aqueous Media: A Long Journey toward the Definition of Structure–Property Relationships
Authors: Esposito Rodolfo , Speciale Immacolata , De Castro Cristina , D’Errico Gerardino , Russo Krauss Irene
Published: March 2023

The need to protect human and environmental health and avoid the widespread use of substances obtained from nonrenewable sources is steering research toward the discovery and development of new molecules characterized by high biocompatibility and biodegradability. Due to their very widespread use, a class of substances for which this need is particularly urgent is that of surfactants. In this respect, an attractive and promising alternative to commonly used synthetic surfactants is represented by so-called biosurfactants, amphiphiles naturally derived from microorganisms. One of the best-known families of biosurfactants is that of rhamnolipids, which are glycolipids with a headgroup formed by one or two rhamnose units. Great scientific and technological effort has been devoted to optimization of their production processes, as well as their physicochemical characterization. However, a conclusive structure–function relationship is far from being defined. In this review, we aim to move a step forward in this direction, by presenting a comprehensive and unified discussion of physicochemical properties of rhamnolipids as a function of solution conditions and rhamnolipid structure. We also discuss still unresolved issues that deserve further investigation in the future, to allow the replacement of conventional surfactants with rhamnolipids.
TRPM7-Mediated Ca2+ Regulates Mussel Settlement through the CaMKKβ-AMPK-SGF1 Pathway
Authors: He Jian , Wang Peng , Wang Zhixuan , Feng Danqing , Zhang Dun
Published: March 2023

Many marine invertebrates have planktonic larval and benthic juvenile/adult stages. When the planktonic larvae are fully developed, they must find a favorable site to settle and metamorphose into benthic juveniles. This transition from a planktonic to a benthic mode of life is a complex behavioral process involving substrate searching and exploration. Although the mechanosensitive receptor in the tactile sensor has been implicated in sensing and responding to surfaces of the substrates, few have been unambiguously identified. Recently, we identified that the mechanosensitive transient receptor potential melastatin-subfamily member 7 (TRPM7) channel, highly expressed in the larval foot of the mussel Mytilospsis sallei, was involved in substrate exploration for settlement. Here, we show that the TRPM7-mediated Ca2+ signal was involved in triggering the larval settlement of M. sallei through the calmodulin-dependent protein kinase kinase β/AMP-activated protein kinase/silk gland factor 1 (CaMKKβ-AMPK-SGF1) pathway. It was found that M. sallei larvae preferred the stiff surfaces for settlement, on which TRPM7, CaMKKβ, AMPK, and SGF1 were highly expressed. These findings will help us to better understand the molecular mechanisms of larval settlement in marine invertebrates, and will provide insights into the potential targets for developing environmentally friendly antifouling coatings for fouling organisms.
Environmental Enrichment Protects against Neurotoxic Effects of Lipopolysaccharide: A Comprehensive Overview
Authors: Landolfo Eugenia , Cutuli Debora , Decandia Davide , Balsamo Francesca , Petrosini Laura , Gelfo Francesca
Published: March 2023

Neuroinflammation is a pathophysiological condition associated with damage to the nervous system. Maternal immune activation and early immune activation have adverse effects on the development of the nervous system and cognitive functions. Neuroinflammation during adulthood leads to neurodegenerative diseases. Lipopolysaccharide (LPS) is used in preclinical research to mimic neurotoxic effects leading to systemic inflammation. Environmental enrichment (EE) has been reported to cause a wide range of beneficial changes in the brain. Based on the above, the purpose of the present review is to describe the effects of exposure to EE paradigms in counteracting LPS-induced neuroinflammation throughout the lifespan. Up to October 2022, a methodical search of studies in the literature, using the PubMed and Scopus databases, was performed, focusing on exposure to LPS, as an inflammatory mediator, and to EE paradigms in preclinical murine models. On the basis of the inclusion criteria, 22 articles were considered and analyzed in the present review. EE exerts sex- and age-dependent neuroprotective and therapeutic effects in animals exposed to the neurotoxic action of LPS. EE’s beneficial effects are present throughout the various ages of life. A healthy lifestyle and stimulating environments are essential to counteract the damages induced by neurotoxic exposure to LPS.
Statins as Potential Preventative Treatment of ETX and Multiple Pore-Forming Toxin-Induced Diseases
Authors: Huang Jing , Zhao Baohua , Liu Tingting , Kang Lin , Li Jiaxin , Guo Zishuo , Chen Ming , Gao Shan , Wang Jing , Li Yanwei , Wang Jinglin , Xin Wenwen
Published: March 2023

Epsilon toxin (ETX), produced by type B and D strains of Clostridium perfringens, can cause fatal enterotoxaemia in ruminant animals, particularly sheep, cattle, and goats. Previous studies show that the cytotoxicity of ETX is dependent on the integrity of lipid rafts, the maintenance of which is ensured by cholesterol. Zaragozic acid (ZA) is a statin drug that reduces the synthesis of squalene, which is responsible for cholesterol synthesis. In this study, ZA significantly reduced the toxicity of ETX in Madin–Darby canine kidney (MDCK) cells. We show that ZA does not affect the binding of ETX to MDCK cells, but propidium iodide staining (PI) and Western blotting confirmed that ZA significantly disrupts the ability of ETX to form pores or oligomers in MDCK cells. Additionally, ZA decreased the phosphatidylserine exposure on the plasma membrane and increased the Ca2+ influx of the cells. Results of density gradient centrifugation suggest that ZA decreased the number of lipid rafts in MDCK membranes, which probably contributed to the attenuation of pore-formation. Moreover, ZA protected mice against ETX in vivo. All mice pre-treated with ZA for 48 h before exposure to an absolute lethal dose of ETX (6400 ng/kg) survived. In summary, these findings provide an innovative method to prevent ETX intoxication. Considering many pore-forming toxins require lipid rafts, we tested and found ZA also inhibited the toxicity of other toxins such as Clostridium perfringens Net B and β-toxin (CPB) and Staphylococcus aureus α-hemolysin (Hla). We expect ZA can thus be developed as a broad-spectrum medicine for the treatment of multiple toxins. In addition, other statins, such as lovastatin (LO), also reduced the toxicity of ETX. These findings indicate that statin medicines are potential candidates for preventing and treating multiple toxin-induced diseases.
Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease
Authors: Al Samarraie Ahmad , Pichette Maxime , Rousseau Guy
Published: March 2023

Atherosclerotic cardiovascular disease (ASCVD) is the primary cause of death globally, with nine million deaths directly attributable to ischemic heart diseases in 2020. Since the last few decades, great effort has been put toward primary and secondary prevention strategies through identification and treatment of major cardiovascular risk factors, including hypertension, diabetes, dyslipidemia, smoking, and a sedentary lifestyle. Once labelled “the forgotten organ”, the gut microbiota has recently been rediscovered and has been found to play key functions in the incidence of ASCVD both directly by contributing to the development of atherosclerosis and indirectly by playing a part in the occurrence of fundamental cardiovascular risk factors. Essential gut metabolites, such as trimethylamine N-oxide (TMAO), secondary bile acids, lipopolysaccharides (LPS), and short-chain fatty acids (SCFAs), have been associated with the extent of ischemic heart diseases. This paper reviews the latest data on the impact of the gut microbiome in the incidence of ASCVD.
Cathepsin S Knockdown Suppresses Endothelial Inflammation, Angiogenesis, and Complement Protein Activity under Hyperglycemic Conditions In Vitro by Inhibiting NF-κB Signaling
Authors: Sayed Shithima , Faruq Omar , Preya Umma Hafsa , Kim Jee Taek
Published: March 2023

Hyperglycemia plays a key role in the development of microvascular complications, endothelial dysfunction (ED), and inflammation. It has been demonstrated that cathepsin S (CTSS) is activated in hyperglycemia and is involved in inducing the release of inflammatory cytokines. We hypothesized that blocking CTSS might alleviate the inflammatory responses and reduce the microvascular complications and angiogenesis in hyperglycemic conditions. In this study, we treated human umbilical vein endothelial cells (HUVECs) with high glucose (HG; 30 mM) to induce hyperglycemia and measured the expression of inflammatory cytokines. When treated with glucose, hyperosmolarity could be linked to cathepsin S expression; however, many have mentioned the high expression of CTSS. Thus, we made an effort to concentrate on the immunomodulatory role of the CTSS knockdown in high glucose conditions. We validated that the HG treatment upregulated the expression of inflammatory cytokines and CTSS in HUVEC. Further, siRNA treatment significantly downregulated CTSS expression along with inflammatory marker levels by inhibiting the nuclear factor-kappa B (NF-κB) mediated signaling pathway. In addition, CTSS silencing led to the decreased expression of vascular endothelial markers and downregulated angiogenic activity in HUVECs, which was confirmed by a tube formation experiment. Concurrently, siRNA treatment reduced the activation of complement proteins C3a and C5a in HUVECs under hyperglycemic conditions. These findings show that CTSS silencing significantly reduces hyperglycemia-induced vascular inflammation. Hence, CTSS may be a novel target for preventing diabetes-induced microvascular complications.
Arteriosclerosis Derived from Cutaneous Inflammation Is Ameliorated by the Deletion of IL-17A and IL-17F
Authors: Nakanishi Takehisa , Iida Shohei , Maruyama Junko , Urushima Hayato , Ichishi Masako , Matsushima Yoshiaki , Mizutani Kento , Nakayama Yuichi , Sugioka Kyoko , Nishimura Mai , Umaoka Ai , Iwakura Yoichiro , Kondo Makoto , Habe Koji , Tsuruta Daisuke , Yamamoto Osamu , Imai Yasutomo , Yamanaka Keiichi
Published: March 2023

The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.
Physiological Roles and Mechanisms of Action of Class I TCP Transcription Factors
Authors: Viola Ivana L. , Alem Antonela L. , Jure Rocío M. , Gonzalez Daniel H.
Published: March 2023

TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTOR 1 and 2 (TCP) proteins constitute a plant-specific transcription factors family exerting effects on multiple aspects of plant development, such as germination, embryogenesis, leaf and flower morphogenesis, and pollen development, through the recruitment of other factors and the modulation of different hormonal pathways. They are divided into two main classes, I and II. This review focuses on the function and regulation of class I TCP proteins (TCPs). We describe the role of class I TCPs in cell growth and proliferation and summarize recent progresses in understanding the function of class I TCPs in diverse developmental processes, defense, and abiotic stress responses. In addition, their function in redox signaling and the interplay between class I TCPs and proteins involved in immunity and transcriptional and posttranslational regulation is discussed.
Antitumor Activity of PEGylated and TEGylated Phenothiazine Derivatives: Structure–Activity Relationship
Authors: Cibotaru Sandu , Sandu Andreea-Isabela , Nicolescu Alina , Marin Luminita
Published: March 2023

The paper aims to investigate the antitumor activity of a series of phenothiazine derivatives in order to establish a structure–antitumor activity relationship. To this end, PEGylated and TEGylated phenothiazine have been functionalized with formyl units and further with sulfonamide units via dynamic imine bonds. Their antitumor activity was monitored in vitro against seven human tumors cell lines and a mouse one compared to a human normal cell line by MTS assay. In order to find the potential influence of different building blocks on antitumor activity, the antioxidant activity, the ability to inhibit farnesyltransferase and the capacity to bind amino acids relevant for tumor cell growth were investigated as well. It was established that different building blocks conferred different functionalities, inducing specific antitumor activity against the tumor cells.
Transcriptomic Analysis Reveals the Detoxification Mechanism of Chilo suppressalis in Response to the Novel Pesticide Cyproflanilide
Authors: Zhou Jungang , Qiu Lin , Liang Qiyao , Zhou Yi , Sun Jinjun , Gao Qiao , He Hualiang , Ding Wenbing , Xue Jin , Li Youzhi
Published: March 2023

Chilo suppressalis is one of the most damaging rice pests in China’s rice-growing regions. Chemical pesticides are the primary method for pest control; the excessive use of insecticides has resulted in pesticide resistance. C. suppressalis is highly susceptible to cyproflanilide, a novel pesticide with high efficacy. However, the acute toxicity and detoxification mechanisms remain unclear. We carried out a bioassay experiment with C. suppressalis larvae and found that the LD10, LD30 and LD50 of cyproflanilide for 3rd instar larvae was 1.7 ng/per larvae, 6.62 ng/per larvae and 16.92 ng/per larvae, respectively. Moreover, our field trial results showed that cyproflanilide had a 91.24% control efficiency against C. suppressalis. We investigated the effect of cyproflanilide (LD30) treatment on the transcriptome profiles of C. suppressalis larvae and found that 483 genes were up-regulated and 305 genes were down-regulated in response to cyproflanilide exposure, with significantly higher CYP4G90 and CYP4AU10 expression in the treatment group. The RNA interference knockdown of CYP4G90 and CYP4AU10 increased mortality by 20% and 18%, respectively, compared to the control. Our results indicate that cyproflanilide has effective insecticidal toxicological activity, and that the CYP4G90 and CYP4AU10 genes are involved in detoxification metabolism. These findings provide an insight into the toxicological basis of cyproflanilide and the means to develop efficient resistance management tools for C. suppressalis.
Targeting Tumor Microenvironment Akt Signaling Represents a Potential Therapeutic Strategy for Aggressive Thyroid Cancer
Authors: Mirshahidi Saied , Yuan Isabella J. , Simental Alfred , Lee Steve C. , Peterson Nathaniel R. , Andrade Filho Pedro A. , Murry Thomas , Duerksen-Hughes Penelope , Yuan Xiangpeng
Published: March 2023

Effects of the tumor microenvironment (TME) stromal cells on progression in thyroid cancer are largely unexplored. Elucidating the effects and underlying mechanisms may facilitate the development of targeting therapy for aggressive cases of this disease. In this study, we investigated the impact of TME stromal cells on cancer stem-like cells (CSCs) in patient-relevant contexts where applying in vitro assays and xenograft models uncovered contributions of TME stromal cells to thyroid cancer progression. We found that TME stromal cells can enhance CSC self-renewal and invasiveness mainly via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. The disruption of Akt signaling could diminish the impact of TME stromal cells on CSC aggressiveness in vitro and reduce CSC tumorigenesis and metastasis in xenografts. Notably, disrupting Akt signaling did not cause detectable alterations in tumor histology and gene expression of major stromal components while it produced therapeutic benefits. In addition, using a clinical cohort, we discovered that papillary thyroid carcinomas with lymph node metastasis are more likely to have elevated Akt signaling compared with the ones without metastasis, suggesting the relevance of Akt-targeting. Overall, our results identify PI3K/Akt pathway-engaged contributions of TME stromal cells to thyroid tumor disease progression, illuminating TME Akt signaling as a therapeutic target in aggressive thyroid cancer.
Acute Toxicity and Stress Behaviour of Heterobranchus bidorsalis Exposed to the Detergent Nittol® NTL
Authors: Ezike Christopher Onyemaechi , Uwadiegwu Chinwe , Agbo Aderonke N.
Published: March 2023

The acute toxicity of the detergent Nittol® 0.8, 1.0, 1.2, 1.4, 1.6, and 0.0 mg NTL/L of clean water on Heterobrunchus bidorsalis, 5.5 ± 0.3 g, 6.4 ± 0.5 cm were investigated, using semi-static bioassay, for 96 h in 50 L capacity plastic test bowls. The fingerlings of the same brood stock and age were collected from Onose Farms Limited, Ughelli, Delta State to the University Research Laboratory, Enugu Lat. 7.4 N; 8°7′5 and long 6°8′ E. 7°6′ W. The test fish were acclimatized for 14 days, and fed at 3% body weight once daily, on a 40% CP commercial diet. Feeding was suspended 24 h before and during the range finding and acute tests. The whole set-up was replicated three times, and no death was recorded during the acclimatization period and in the control. A total of 180 fingerlings were used, and 10 fingerlings were assigned to each replicate. The test set-up was monitored daily for water quality parameters, opercular ventilation, tail fin beat frequency, and mortality. Dose and time-dependent behavioural patterns exhibited by the test fish, during the exposure periods include rapid swimming, air gulping, loss of balance, and a period of convulsion before death. Significant elevation in pH and temperature, reduction of DO compared to the control (p < 0.05) in the water quality, and dose-dependent early elevation of the tail and fin movements declined towards the end of the experiment. The 96 h LC50 was determined to be 1.41 mg/L, indicating that the detergent NTL is toxic to the test fish. The haematological parameters were significantly (p < 0.05) reduced in the treated ranges of RBC 5.20 ± 0.07–8.00 ± 0.02 × 106 mm3, HB 7.53 ± 0.50–10.72 ± 0.14 g/dl, PCV 13.20 ± 0.8.50–18.00 ± 0.43 % below their elevated respective controls of 10.50 ± 0.01 × 10 6 mm3, 11.00 ± 0.01 g/dl, and 23.48 ± 0.2.6 %. The white blood cells (WBC) recorded a significant (p < 0.05) increase in ranges of 23.72 ± 0.14–51.80 ± 1.9 × 103 mm3 above the control value of 11.00 ± 0.01 × 103 mm3 Therefore, values greater than the safe amount of 0.014 mg/L should not be allowed in the receiving culture waters for Heterobrunchus bidorsalis fingerlings.
Correction: McCordic et al. The Household Food Security Implications of Disrupted Access to Basic Services in Five Cities in the Global South. Land 2022, 11, 654
Authors: McCordic Cameron , Frayne Bruce , Sunu Naomi , Williamson Clare
Published: March 2023

In the original publication [...]
Analyzing Transregional Vernacular Cultural Landscape Security Patterns with a Nature–Culture Lens: A Case Study of the Yangtze River Delta Demonstration Area, China
Authors: Yan Jiaying , Du Shuang , Zhang Jinbo , Yu Weiyu
Published: March 2023

Cultural landscape security is important to national spatial and cultural security. However, compared with the many achievements in the study of ecological security, transregional cultural landscape security research lacks enough attention to match its importance. In the context of advocacy of ‘connecting practices’ between nature and culture in the field of international heritage conservation, this paper developed an approach for constructing transregional vernacular cultural landscape security patterns and identifying the key protected areas. A method is put forward based on the case of the Yangtze River Delta Demonstration Area, one of the fastest urbanizing regions in China, and included the following three steps: (1) analyze the core values of the transregional vernacular cultural landscape from a long-time series and multi-scale perspective; (2) integrate ecological security assessment and value security evaluation by combining qualitative with quantitative methods; (3) build a comprehensive vernacular cultural landscape security pattern to identify key protected areas and develop a zoning and grading conservation strategy toolkit. The results proved that our new method could effectively build a cross-regional network of integrated spatial and functional relationships between the historical cultural and natural landscape and have great significance in improving the level of transregional territorial spatial governance.
Spatial and Temporal Characteristics of Dust Storms and Aeolian Processes in the Southern Balkash Deserts in Kazakhstan, Central Asia
Authors: Issanova Gulnura , Kaldybayev Azamat , Ge Yongxiao , Abuduwaili Jilili , Ma Long
Published: March 2023

Sand and dust storms are hazardous to the environment and have a significant role in desertification. Under the influence of climate change and human activities, dust storms and aeolian processes have been common phenomena in the Southern Balkash deserts in Kazakhstan, Central Asia. However, knowledge gaps on spatial and temporal characteristics of dust storms and aeolian process in the Southern Balkash deserts still exist. Therefore, in present study, meteorological observations and numerous cartographic materials were used to identify the powerful sources with the highest frequency of dust storms and aeolian processes in the Southern Balkash deserts. The result showed that the Southern Balkash deserts were covered mainly by transverse parabolic sands (48%), dome dunes (24%), and transverse dome dunes (23%), where the aeolian processes occurred to a significant degree. Significant and strong degrees of aeolian processes occurred in most of the Southern Balkash deserts. The eastern part of the Taukum and the northern part of the Zhamankum and Karakum deserts were prone to aeolian processes to a substantial degree. The Moiynkum, Bestas, Saryesikatyrau, and Taukum deserts had the most frequent storms, occuring, on average, 17 to 43 days/per year. The occurrence of dust storms has been of a stable decreasing trend since the 1990s, except for 2008–2009. Aeolian dust in the Southern Balkash deserts flowed mainly from the western and southwestern to the eastern and northeastern. The results of the present study shed light on the temporal and spatial characteristics of dust storms and aeolian processes in the Southern Balkash deserts. This is of great importance in helping to monitor and predict dust storms and motion patterns of aeolian dust in this region.
The Minimum Number of Ablation Lines for Complete Isolation of the Pulmonary Veins during Thoracoscopic Ablation for Atrial Fibrillation
Authors: Choi Min Suk , Lee Yoonseo , Jeong Dong Seop
Published: March 2023

Total thoracoscopic ablation has been recommended as a class IIa indication for atrial fibrillation. However, the optimal number of ablation lines for pulmonary vein isolation has not yet been proposed. This study aimed to report the minimum number of ablation lines required to achieve an intraoperative conduction block. This study included a total of 20 patients who underwent total thoracoscopic ablation from December 2020 to July 2021. The epicardial conduction block was checked after each ablation line of pulmonary vein antral clamping. The median age was 61 years old. The median duration of atrial fibrillation since the first diagnosis was 78 months. Pulmonary vein isolation with bidirectional conduction block was confirmed in 90% of patients. A median of six ablation lines around each pulmonary vein antrum were performed according to our protocol even after the conduction block was verified. The median number of ablations to achieve an exit block was two on the right side and 3.5 on the left side. We found that most conduction blocks were achieved within three ablations around the pulmonary vein antrum. Our results may provide evidence to reduce the number of unnecessary ablation lines in the future.
Unresectable Hepatocellular Carcinoma: A Review of New Advances with Focus on Targeted Therapy and Immunotherapy
Authors: Farasati Far Bahareh , Rabie Dorsa , Hemati Parisa , Fooladpanjeh Parastoo , Faal Hamedanchi Neda , Broomand Lomer Nima , Karimi Rouzbahani Arian , Naimi-Jamal Mohammad Reza
Published: March 2023

With an expected incidence of more than 1 million cases by 2025, liver cancer remains a problem for world health. With over 90% of cases, hepatocellular carcinoma (HCC) is the most prevalent kind of liver cancer. In this review, we presented the range of experimental therapeutics for patients with advanced HCC, the successes and failures of new treatments, areas for future development, the evaluation of dose-limiting toxicity in different drugs, and the safety profile in patients with liver dysfunction related to the underlying chronic liver disease. In addition to the unmet demand for biomarkers to guide treatment decisions and the burgeoning fields of immunotherapy and systemic therapy in hepatocellular carcinoma, the development of old and new drugs, including their failures and current advancements, has been reviewed. This review aims to evaluate the updated optimal clinical treatment of unresectable hepatocellular carcinomas in clinical practice, mainly through targeted therapy. Although surgical treatment can significantly enhance the survival probability of early and intermediate-stage patients, it is unsuitable for most HCC patients due to a lack of donors. Due to their severe toxicity, the few first-line anti-HCC drugs, such as sorafenib, are often reserved for advanced HCC patients for whom other therapies have failed. The second-line drugs are usually alternatives for patients with intolerance or resistance. Consequently, the ongoing growth of possible preclinical drugs and studies on miRNAs, lncRNAs, and numerous other signaling pathway targets for developing novel drugs may introduce additional treatment prospects for HCC.
Computational Analysis of Liquid Hydrogen Storage Tanks for Aircraft Applications
Authors: Mantzaroudis Vasileios K. , Theotokoglou Efstathios E.
Published: March 2023

During the last two decades, the use of hydrogen (H2) as fuel for aircraft applications has been drawing attention; more specifically, its storage in liquid state (LH2), which is performed in extreme cryogenic temperatures (−253 °C), is a matter of research. The motivation for this effort is enhanced by the predicted growth of the aviation sector; however, it is estimated that this growth could be sustainable only if the strategies and objectives set by global organizations for the elimination of greenhouse gas emissions during the next decades, such as the European Green Deal, are taken into consideration and, consequently, technologies such as hydrogen fuel are promoted. Regarding LH2 in aircraft, substantial effort is required to design, analyze and manufacture suitable tanks for efficient storage. Important tools in this process are computational methods provided by advanced engineering software (CAD/CAE). In the present work, a computational study with the finite element method is performed in order to parametrically analyze proper tanks, examining the effect of the LH2 level stored as well as the tank geometric configuration. In the process, the need for powerful numerical models is demonstrated, owing to the highly non-linear dependence on temperature of the involved materials. The present numerical models’ efficiency could be further enhanced by integrating them as part of a total aircraft configuration design loop.
New Results on Finite-Time Synchronization of Complex-Valued BAM Neural Networks with Time Delays by the Quadratic Analysis Approach
Authors: Yang Zhen , Zhang Zhengqiu
Published: March 2023

In this paper, we are interested in the finite-time synchronization of complex-valued BAM neural networks with time delays. Without applying Lyapunov–Krasovskii functional theory, finite-time convergence theorem, graph-theoretic method, the theory of complex functions or the integral inequality method, by using the quadratic analysis approach, inequality techniques and designing two classes of novel controllers, two novel sufficient conditions are achieved to guarantee finite-time synchronization between the master system and the slave system. The quadratic analysis method used in our paper is a different study approach of finite-time synchronization from those in existing papers. Therefore the controllers designed in our paper are fully novel.
Effect of Storage Time and Temperature on the Bioactivity of a Chitosan-Derived Epigenetic Modulation Scaffold
Authors: Sukpaita Teerawat , Chirachanchai Suwabun , Pimkhaokham Atiphan , Ampornaramveth Ruchanee
Published: March 2023

The appropriate storage protocol is one of the main limitations of translating tissue engineering technology to commercialized clinical applications. Recently, the development of a chitosan-derived composite scaffold incorporated with bioactive molecules has been reported as an excellent material to repair a critical size bony defect in mice calvaria. This study aims to determine the storage time and appropriate storage temperature of Chitosan/Biphasic Calcium Phosphate/Trichostatin A composite scaffold (CS/BCP/TSA scaffold) in vitro. The mechanical properties and in vitro bioactivity of trichostatin A (TSA) released from CS/BCP/TSA scaffolds in different storage times and temperatures were evaluated. Different storage times (0, 14, and 28 days) and temperatures (−18, 4, and 25 °C) did not affect the porosity, compressive strength, shape memory, and amount of TSA released. However, scaffolds stored at 25 °C and 4 °C were found to lose their bioactivity after 3- and 7-day storage periods, respectively. Thus, the CS/BCP/TSA scaffold should be stored in freezing conditions to preserve the long-term stability of TSA.
MicroRNAs: Potential Biomarkers of Disease Severity in Chronic Rhinosinusitis with Nasal Polyps
Authors: Gata Anda , Neagoe Ioana Berindan , Leucuta Daniel-Corneliu , Budisan Liviuta , Raduly Lajos , Trombitas Veronica Elena , Albu Silviu
Published: March 2023

Background and Objectives: Chronic rhinosinusitis with nasal polyps (CRwNP) has multiple clinical presentations, and predictors of successful treatment are correlated to different parameters. Differentially expressed microRNAs in nasal polyps emerge as possible facilitators of precise endotyping in this disease. We aimed to evaluate the correlation between the clinical parameters of CRSwNP and two different microRNAs. Materials and Methods: The expression of miR-125b and miR-203a-3p in nasal polyps (n = 86) and normal nasal mucosa (n = 20) was determined through microarray analysis. Preoperative workup included CT scan, nasal endoscopy, blood tests, symptoms and depression questionnaires. Results: MiR-125b showed significant overexpression in NP compared to the normal nasal mucosa. miR-125b expression levels were positively and significantly correlated with blood eosinophilia (p = 0.018) and nasal endoscopy score (p = 0.021). Although high CT scores were related to miR-125b overexpression, the correlation did not reach statistical significance. miR-203a-3p was underexpressed in nasal polyps and was significantly underexpressed in CRSwNP patients with environmental allergies. Conclusions: Both miR-125b and miR-203a-3p are potential biomarkers in CRSwNP. miR-125b also correlates with the clinical picture, while miR-203a-3p could help identify an associated allergy.
Atherosclerotic Cardiovascular Disease in Inflammatory Bowel Disease: The Role of Chronic Inflammation and Platelet Aggregation
Authors: Lugonja Sofija I. , Pantic Ivana L. , Milovanovic Tamara M. , Grbovic Vesna M. , Djokovic Bojana M. , Todorovic Željko D. , Simovic Stefan M. , Medovic Raša H. , Zdravkovic Nebojsa D. , Zdravkovic Natasa D.
Published: March 2023

Background and Objectives: Atherosclerosis is one of inflammatory bowel disease’s most significant cardiovascular manifestations. This research aimed to examine the relationship between biochemical, haemostatic, and immune parameters of atherosclerosis and ulcerative colitis patients and its relationship to platelet aggregation. Materials and Methods: A clinical, observational cross-sectional study was performed, during which the tested parameters were compared in the experimental and control groups. The patients were divided into four groups. The first group had 25 patients who had ulcerative colitis and atherosclerosis. The second group included 39 patients with ulcerative colitis without atherosclerosis. The third group comprised 31 patients suffering from atherosclerosis without ulcerative colitis, and the fourth group comprised 25 healthy subjects. Results: In our study, we registered statistically higher levels of inflammatory markers like SE, CRP, Le, fecal calprotectin, TNF-α, and IL-6, as well as the higher value of thrombocytes and thrombocyte aggregation in the group of patients with ulcerative colitis compared to the control group. Lower levels of total cholesterol and LDL were also recorded in patients with ulcerative colitis and atherosclerosis and ulcerative colitis without atherosclerosis compared to healthy control. Triglyceride and remnant cholesterol were higher in patients with ulcerative colitis and atherosclerosis when compared to patients with ulcerative colitis and healthy control but lower than in patients with atherosclerosis only. Conclusions: Several inflammatory markers and platelet aggregation could be good discrimination markers for subjects with ulcerative colitis with the highest risk of atherosclerosis.
Does Proton Pump Inhibitors Decrease the Efficacy of Palbociclib and Ribociclib in Patients with Metastatic Breast Cancer?
Authors: Odabas Hatice , Dogan Akif , Ozcelik Melike , Yildirim Sedat , Ozkerim Ugur , Turan Nedim , Yildirim Mahmut Emre , Gumus Mahmut
Published: March 2023

Background and Objectives: This investigation aimed to determine the impacts of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer managed with palbociclib or ribociclib as either the initial or subsequent line of therapy option. Materials and Methods: In this retrospective study, patients were classified as “concurrent PPIs” if PPIs were given for at least two-thirds of the palbociclib or ribociclib therapy period, and “no concurrent PPIs” if no PPIs were given during the period of palbociclib or ribociclib therapy. Each patient was also classified as endocrine-sensitive or endocrine-resistant according to the duration of previous endocrine responses. “Concurrent PPIs” and “no concurrent PPIs” groups were compared with each other in terms of PFS. This comparison was performed for both ribociclib and palbociclib groups. Results: The research included 220 patients in total. The PFS of 57 patients on palbociclib using concomitant PPIs was 14.4 months. Among 63 patients using palbociclib without concomitant PPIs, the PFS was 15.8 months. No statistically significant difference was found with PPI use (p = 0.82). Among 29 patients using ribociclib concurrently with PPIs, the PFS was 22.4 months. Among 71 patients using ribociclib without PPIs, the PFS was 20.2 months. No statistically significant difference was found with PPI use (p = 0.40). Conclusion: The results of our investigation showed that concomitant use of the most commonly used PPIs in the study (lansoprazole, pantoprazole, and esomeprazole) with palbociclib or ribociclib did not have any detrimental effects on PFS. Where appropriate, PPIs can be used concurrently with palbociclib and ribociclib. However, the effect of PPIs on cycling-dependent kinase 4/6 inhibitors deserves further investigation.