bluuebunny/crossref_metadata_2025 huggingface dataset:
On-Line Thermally Induced Evolved Gas Analysis: An Update—Part 2: EGA-FTIR
Authors: Gullifa Giuseppina , Barone Laura , Papa Elena , Materazzi Stefano , Risoluti Roberta
Published: December 2022

The on-line thermally induced evolved gas analysis (OLTI-EGA) is widely applied in many different fields. Aimed to update the applications, our group has systematically collected and published examples of EGA characterizations. Following the recently published review on EGA-MS applications, this second part reviews the latest applications of Evolved Gas Analysis performed by on-line coupling heating devices to infrared spectrometers (EGA-FTIR). The selected 2019, 2020, 2021 and early 2022 references are collected and briefly described in this review; these are useful to help researchers to easily find applications that are sometimes difficult to locate.
Enzymatic Synthesis of Vancomycin-Modified DNA
Authors: Figazzolo Chiara , Bonhomme Frédéric , Saidjalolov Saidbakhrom , Ethève-Quelquejeu Mélanie , Hollenstein Marcel
Published: December 2022

Many potent antibiotics fail to treat bacterial infections due to emergence of drug-resistant strains. This surge of antimicrobial resistance (AMR) calls in for the development of alternative strategies and methods for the development of drugs with restored bactericidal activities. In this context, we surmised that identifying aptamers using nucleotides connected to antibiotics will lead to chemically modified aptameric species capable of restoring the original binding activity of the drugs and hence produce active antibiotic species that could be used to combat AMR. Here, we report the synthesis of a modified nucleoside triphosphate equipped with a vancomycin moiety on the nucleobase. We demonstrate that this nucleotide analogue is suitable for polymerase-mediated synthesis of modified DNA and, importantly, highlight its compatibility with the SELEX methodology. These results pave the way for bacterial-SELEX for the identification of vancomycin-modified aptamers.
patchIT: A Multipurpose Patch Creation Tool for Image Processing Applications
Authors: Kesidis Anastasios L. , Krassanakis Vassilios , Misthos Loukas-Moysis , Merlemis Nikolaos
Published: December 2022

Patch-based approaches in image processing are often preferable to working with the entire image. They provide an alternative representation of the image as a set of partial local sub-images (patches) which is a vital preprocessing step in many image processing applications. In this paper, a new software tool called patchIT is presented, providing an integrated framework suitable for the systematic and automatized extraction of patches from images based on user-defined geometrical and spatial criteria. Patches can be extracted in both a sliding and random manner and can be exported either as images, MATLAB .mat files, or raw text files. The proposed tool offers further functionality, including masking operations that act as spatial filters, identifying candidate patch areas, as well as geometric transformations by applying patch value indexing. It also efficiently handles issues that arise in large-scale patch processing scenarios in terms of memory and time requirements. In addition, a use case in cartographic research is presented that utilizes patchIT for map evaluation purposes based on a visual heterogeneity indicator. The tool supports all common image file formats and efficiently processes bitonal, grayscale, color, and multispectral images. PatchIT is freely available to the scientific community under the third version of GNU General Public License (GPL v3) on the GitHub platform.
Improving the Stability of Halide Perovskite Solar Cells Using Nanoparticles of Tungsten Disulfide
Authors: Immanuel Philip Nathaniel , Huang Song-Jeng , Danchuk Viktor , Sedova Anastasiya , Prilusky Johnathan , Goldreich Achiad , Shalom Hila , Musin Albina , Yadgarov Lena
Published: December 2022

Halide perovskites-based solar cells are drawing significant attention due to their high efficiency, versatility, and affordable processing. Hence, halide perovskite solar cells have great potential to be commercialized. However, the halide perovskites (HPs) are not stable in an ambient environment. Thus, the instability of the perovskite is an essential issue that needs to be addressed to allow its rapid commercialization. In this work, WS2 nanoparticles (NPs) are successfully implemented on methylammonium lead iodide (MAPbI3) based halide perovskite solar cells. The main role of the WS2 NPs in the halide perovskite solar cells is as stabilizing agent. Here the WS2 NPs act as heat dissipater and charge transfer channels, thus allowing an effective charge separation. The electron extraction by the WS2 NPs from the adjacent MAPbI3 is efficient and results in a higher current density. In addition, the structural analysis of the MAPbI3 films indicates that the WS2 NPs act as nucleation sites, thus promoting the formation of larger grains of MAPbI3. Remarkably, the absorption and shelf life of the MAPbI3 layers have increased by 1.7 and 4.5-fold, respectively. Our results demonstrate a significant improvement in stability and solar cell characteristics. This paves the way for the long-term stabilization of HPs solar cells by the implementation of WS2 NPs.
Preparation of Solid Lipid Nanoparticles of Cinnamaldehyde and Determination of Sustained Release Capacity
Authors: Chen Jiajia , Li Shangjian , Zheng Qinhua , Feng Xiaolin , Tan Weijian , Feng Kexin , Liu Yuntong , Hu Wenzhong
Published: December 2022

Natural plant essential oils cannot be applied on a large scale due to their high volatility, easy deactivation, etc. This study provides a new method to prepare a long-lasting, slow-release essential oil product by taking advantage of solid lipid nanoparticles, which will provide a scientific guideline for the future essential oil industry. In this article, solid lipid cinnamaldehyde nanoparticles were prepared using an ultrahigh-pressure homogenization method. SLN-CA with a particle size of 74 ± 5 nm, PDI of 0.153 ± 0.032, and zeta potential of −44.36 ± 2.2 mV was screened using an additional amount of cinnamaldehyde, the ratio of oil phase components, and the homogenization pressure and number of times as factors. Differential thermal analysis and spectroscopy demonstrated that cinnamaldehyde was successfully encapsulated inside the nanoparticles. The change in particle size of nanoparticles under different conditions and times was used as an indicator of stability. The stability of the finished nanoparticles was evaluated. The retention and slow-release ability of cinnamaldehyde were investigated using the concentration of cinnamaldehyde in nanoparticles as an indicator. The results showed that after 15 days, SLN-CA retained 52.36% of the concentration from 15 days prior. The bacterial inhibition test shows that SLN-CA can inhibit bacteria
Anti-Obesity Effects of Formulated Biscuits Supplemented with Date’s Fiber; Agro-Waste Products Used as a Potent Functional Food
Authors: Aljutaily Thamer , Elbeltagy Alaa , Ali Asmahan A. , Gadallah Mohamed G. E. , Khalil Nazeha A.
Published: December 2022

Superabundant date fruit production in Al-Qassim in the Kingdom of Saudi Arabia (KSA), a plentiful region for producing date syrup resulting in massive amounts of date fiber (DF), causes environmental issues with what is considered dietary waste. However, no food producer or researcher has thought of the valorization of DF by extracting the crude polysaccharides that can be converted to nanoparticles (flours) to increase its functional group and enhance its functionality. Using the DF was the primary goal, with the new biscuits used within the current study investigated as a potent integrated approach for controlling obesity levels and its effects. Obesity is one of the most important human problems worldwide, connected to many metabolic diseases, e.g., diabetes mellitus and cardiovascular disease. Its prevalence has recently increased among Saudi children and adolescents. An investigation of the biological effects of the formulated products was carried out by feeding the formulated biscuits with different DF levels (5, 10 and 15%) to obese albino rats, in addition to positive and negative control groups, to evaluate the effect of a reduced calorie product on controlling their body weight and health stats (lipid profile, blood sugars, kidney and liver functions). The collected data showed that the most positive results were obtained from rats fed diets supplemented with 10% DF biscuits. All TCHO, TrGs, HDL, and HDL were decreased to the best levels in this group compared to the positive control group (148.23, 145.30, 37.50, and 81.67 vs. 238.37, 199.07, 62.57, and 135.99, respectively). To conclude, DF supplementation presented anti-obesity properties in animal models; however, more epidemiological trials are needed.
Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy
Authors: Deluque Amanda Lima , Oliveira Beatriz Magalhães , Souza Cláudia Silva , Maciel Ana Lívia Dias , Francescato Heloísa Della Coletta , Giovanini Cleonice , de Almeida Lucas Ferreira , de Paula Francisco José Albuquerque , Costa Roberto Silva , Antunes-Rodrigues José , Coimbra Terezila Machado
Published: December 2022

Renal endothelial cell (EC) injury and microvascular dysfunction contribute to chronic kidney disease (CKD). In recent years, increasing evidence has suggested that EC undergoes an endothelial-to-mesenchymal transition (EndoMT), which might promote fibrosis. Adriamycin (ADR) induces glomerular endothelial dysfunction, which leads to progressive proteinuria in rodents. The activation of the vitamin D receptor (VDR) plays a crucial role in endothelial function modulation, cell differentiation, and suppression of the expression of fibrotic markers by regulating the production of nitric oxide (NO) by activating the endothelial NO synthase (eNOS) in the kidneys. This study aimed to evaluate the effect of paricalcitol treatment on renal endothelial toxicity in a model of CKD induced by ADR in rats and explore mechanisms involved in EC maintenance by eNOS/NO, angiopoietins (Angs)/endothelium cell-specific receptor tyrosine kinase (Tie-2, also known as TEK) and vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) axis. The results show that paricalcitol attenuated the renal damage ADR-induced with antiproteinuric effects, glomerular and tubular structure, and function protection. Furthermore, activation of the VDR promoted the maintenance of the function and structure of glomerular, cortical, and external medullary endothelial cells by regulating NO production. In addition, it suppressed the expression of the mesenchymal markers in renal tissue through attenuation of (transforming growth factor-beta) TGF-β1/Smad2/3-dependent and downregulated of Ang-2/Tie-2 axis. It regulated the VEGF/VEGFR2 pathway, which was ADR-deregulated. These effects were associated with lower AT1 expression and VDR recovery to renal tissue after paricalcitol treatment. Our results showed a protective role of paricalcitol in the renal microvasculature that could be used as a target for treating the beginning of CKD.
Dietary Inflammatory Index and Associations with Sarcopenia Symptomology in Community-Dwelling Older Adults
Authors: Linton Corey , Wright Hattie H. , Wadsworth Daniel P. , Schaumberg Mia A.
Published: December 2022

Low-grade systemic inflammation is a key driver of muscle degeneration in older adults, and diets with pro-inflammatory properties may further contribute to loss of muscle mass, strength and function. Therefore, this research aimed to explore the associations between the inflammatory potential of the diet and measures of sarcopenia symptomology in community-dwelling older adults. Upper (handgrip strength, HGS) and lower extremity (sit-to-stand) muscle strength, physical performance (timed-up-and-go, TUG) and appendicular skeletal muscle mass (ASM) was assessed according to the European Working Group on Sarcopenia in Older People version 2 (EWGSOP2) criteria. Multiple 24-hr dietary recalls were used to calculate the Dietary Inflammatory Index (DII), which was then used to group participants into anti- and pro-inflammatory dietary groups. Multiple linear regression investigated associations between DII, muscle strength, physical performance, and muscle quantity adjusted for age, gender, comorbidities, waist circumference and physical activity. Adults 65–85 years (n = 110, 72.1 ± 4.7 years, 76.4% female) were recruited. One participant was identified with sarcopenia, 35.2% were pre-frail, or frail. More participants with a pro-inflammatory DII score had low muscle quantity than those with anti-inflammatory DII (3.4% vs. 6.4%, x2 = 4.537, p = 0.043) and DII was negatively associated with HGS (β = −0.157, p = 0.016) and ASM (β = −0.176, p = 0.002) which remained significant after adjusting for covariates. In this population, DII was associated with less favorable muscle strength, physical performance, and muscle quantity.
Nutritional Biomarkers and Heart Rate Variability in Patients with Subacute Stroke
Authors: Park Eo Jin , Yoo Seung Don
Published: December 2022

Malnutrition and autonomic dysfunction are associated with poor outcomes, mortality, and psychological problems after stroke. Relevant laboratory biomarkers include serum albumin, prealbumin, and transferrin. Heart rate variability (HRV), a noninvasive measurement, can objectively measure autonomic nervous system (ANS) function. The relationship between HRV and nutritional biomarkers in stroke patients has not been studied. This study aimed to examine the relationship between nutritional biomarkers and HRV parameters in stroke patients. We retrospectively recruited 426 patients with subacute stroke who were examined for nutritional biomarkers, such as serum albumin, prealbumin, and transferrin, and underwent 24 h ambulatory Holter electrocardiography. Patients were divided into groups according to their nutritional biomarker status. Differences in HRV parameters between nutritional biomarker-deficient and normal groups were assessed. Pearson’s correlation and multiple regression analyses were used to verify the relationship between HRV parameters and nutritional biomarkers. HRV parameters were significantly lower in the nutritional biomarker-deficient groups. In addition, there was a significant association between HRV parameters and nutritional biomarkers. Serum albumin, prealbumin, and transferrin levels were associated with ANS function, as measured by HRV, and their deficiency may be a predictive factor for the severity of ANS dysfunction in stroke patients.
Associations between Dietary Intake of Vitamin D, Sun Exposure, and Generalized Anxiety among College Women
Authors: Al Anouti Fatme , Grant William , Thomas Justin , AlBlooshi Sharifa , Karras Spyridon
Published: December 2022

Vitamin D insufficiency impacts about half of the population worldwide. Almost one billion individuals across all ages and ethnicities suffer from vitamin D deficiency. Hypovitaminosis D is mainly related to lifestyle choices and habits, such as outdoor activities and food intake. Several studies have demonstrated a correlation between vitamin D status and anxiety symptoms. The main purpose of this study was to investigate the correlation between anxiety and factors including age, vitamin D deficiency, citizens, dietary and supplementary vitamin D intake, along with sun exposure, among a sample of female college students in the United Arab Emirates. A descriptive questionnaire, including a short version of the generalized anxiety disorder scale, food frequency questionnaire, and sun avoidance inventory, was used to assess the relationship between the dietary intake of vitamin D-rich foods and supplements, along with sun avoidance/exposure and generalized anxiety, among a total of 386 female participants aged 18 and above. The findings showed clear evidence that sun avoidance behaviors are strongly associated with an elevated risk of generalized anxiety disorder among adult females in the United Arab Emirates.
Association between Fathers’ and Mothers’ Parenting Styles and the Risk of Overweight/Obesity among Adolescents in San José Province, Costa Rica
Authors: Monge-Rojas Rafael , Smith-Castro Vanessa , O’Connor Teresia M. , Vargas-Quesada Rulamán , Reyes-Fernández Benjamín
Published: December 2022

Parenting styles are a risk factor for adolescents overweight/obesity worldwide, but this association is not well understood in the context of Latin America. This study examines the association between the parenting styles of mothers and fathers and the risk of overweight/obesity among Costa Rican adolescents. Data are cross-sectional from a sample of adolescents (13–18 years old) enrolled in ten urban and eight rural schools (n = 18) in the province of San José, Costa Rica, in 2017. Hierarchical logistic regression analyses were performed to assess the likelihood of adolescents being overweight according to the mothers’ and fathers’ parenting styles. A significant association was found between the risk of adolescent overweight/obesity and the paternal authoritarian style only in rural areas (B = 0.622, SE = 0.317, Wald = 3.864, ExpB = 1.863, p = 0.04), and between said risk and the paternal permissive style only in male adolescents (B = 0.901, SE = 0.435, Wald = 4.286, ExpB = 2.461, p = 0.038). For maternal parenting styles, no associations reached significant levels once logistic regression models were adjusted for the fathers’ parenting styles. These findings underscore the importance of further studying the role of fathers’ paternal parenting styles on Latin American adolescent weight outcomes. Expanding our understanding of the parenting styles of fathers has important implications for the design and implementation of culturally- and gender-appropriate family interventions.
The Impact of Serum Levels of Vitamin D3 and Its Metabolites on the Prognosis and Disease Severity of COVID-19
Authors: Khojah Hani M. J. , Ahmed Sameh A. , Al-Thagfan Sultan S. , Alahmadi Yaser M. , Abdou Yasser A.
Published: December 2022

Vitamin D is among the increasingly consumed dietary supplements during the COVID-19 pandemic. It plays a regulatory role in the immune system and moderates the renin–angiotensin system, which is implicated in infection pathogenesis. However, the investigation of serum levels of vitamin D3 forms and their relative ratios in COVID-19 patients is worth investigation to understand the impacts of disease severity. Hence, we investigated the serum levels of vitamin D3 (cholecalciferol) and its metabolites (calcifediol and calcitriol), in addition to their relative ratios and correlations with angiotensin-converting enzyme 2 (ACE2), interleukin-6 (Il-6), and neutrophil–lymphocyte ratio (NLR) in COVID-19 patients compared with healthy controls. Oropharyngeal specimens were collected from the study subjects for polymerase chain reaction testing for COVID-19. Whole blood samples were obtained for blood count and NLR testing, and sera were used for the analysis of the levels of the vitamin and its metabolites, ACE2, and IL-6. We enrolled 103 patients and 50 controls. ACE2, Il-6, and NLR were significantly higher in the patients group (72.37 ± 18.67 vs. 32.36 ± 11.27 U/L, 95.84 ± 25.23 vs. 2.76 ± 0.62 pg/mL, and 1.61 ± 0.30 vs. 1.07 ± 0.16, respectively). Cholecalciferol, calcifediol, and calcitriol were significantly lower in patients (18.50 ± 5.36 vs. 29.13 ± 4.94 ng/mL, 14.60 ± 3.30 vs. 23.10 ± 3.02 ng/mL, and 42.90 ± 8.44 vs. 65.15 ± 7.11 pg/mL, respectively). However, their relative ratios were normal in both groups. Levels of the vitamin and metabolites were strongly positively, strongly negatively, and moderately negatively correlated with ACE2, Il-6, and NLR, respectively. COVID-19 infection severity is associated with a significant decrease in vitamin D3 and its metabolites in a parallel pattern, and with a significant increase in ACE2, Il-6, and NLR. Higher levels of vitamin D and its metabolites are potentially protective against severe infection.
Relationship between Preoperative Nutritional Status and Clinical Outcomes in Patients with Head and Neck Cancer
Authors: Wang En-Ying , Chen Mu-Kuan , Hsieh Ming-Yu , Kor Chew-Teng , Liu Yen-Tze
Published: December 2022

The nutritional status in cancer patients is related to cancer survival and surgical outcome. The objective of this study was to examine the relationship between preoperative prognostic nutritional index (PNI) and post-operative clinical outcomes in head and neck cancer (HNC) patients. A total of 1282 head and neck cancer patients receiving surgical resection in Changhua Christian Hospital between 1 January 2010 and 30 August 2021 were recruited in the final analysis after undergoing propensity score matching analysis. The logistic regression model was used to assess the association of the PNI group with overall and various complications. The patients in the high PNI group had a significant lower incidence of overall complications, medical complications, and pulmonary complications; but not significant surgical complications. The high PNI group had lower mortality risk. The results in this study revealed that PNI score was a significant independent predictor of postoperative complications in HNC patients undergoing surgical resection. We recommend preoperative testing and evaluation of HNC patients to identify low PNI and high-risk groups for postoperative surveillance.
Complete Recovery of an Iatrogenic Venous Gaseous Embolism (VGE) Clinical Presentation Thanks to a Timely Hyperbaric Oxygen Therapy (HBOT) Treatment
Authors: Zanon Vincenzo , Magri Silvia , Bonera Giulia , Camporesi Enrico
Published: December 2022

Gas embolism is a potentially fatal occurrence in which bubbles are introduced into the arterial/venous circulation. A multifocal ischemia could be the life-threatening scenario of that and occurring after diving-related activities, or pulmonary barotrauma, or even iatrogenic procedure capable to cause an accidental introduction of gas into the vasculature. The case here reported concerns the good outcome of one of these rare occurrences thanks to a prompt diagnosis and proper management of the ongoing gaseous lesion. Unfortunately, it remains ethically and technically complex to consider feasible Randomized Clinical Trials (RCTs) in hyperbaric medicine in general, and even more so in this type of eventuality. We are happy to share this further favorable result as we believe it is just thanks to growing documented clinical evidence that now anyone, if ever had to be suffering from gas embolism, in presence of a RCT would widely prefer to be included in the arm that can take advantage of oxygen hyperbaric (HBO) therapy.
Artificial Insemination as an Alternative Transmission Route for African Swine Fever Virus
Authors: Friedrichs Virginia , Reicks Darwin , Hasenfuß Tobias , Gerstenkorn Elisabeth , Zimmerman Jeffrey J. , Nelson Eric A. , Carrau Tessa , Deutschmann Paul , Sehl-Ewert Julia , Roszyk Hanna , Beer Martin , Christopher-Hennings Jane , Blome Sandra
Published: December 2022

The rapid spread of the African swine fever virus (ASFV), causing severe disease with often high fatality rates in Eurasian suids, prevails as a threat for pig populations and dependent industries worldwide. Although advancing scientific progress continually enhances our understanding of ASFV pathogenesis, alternative transmission routes for ASFV have yet to be assessed. Here, we demonstrate that ASFV can efficiently be transferred from infected boars to naïve recipient gilts through artificial insemination (AI). In modern pig production, semen from boar studs often supplies many sow herds. Thus, the infection of a boar stud presents the risk of rapidly and widely distributing ASFV within or between countries. Daily blood and semen collection from four boars after intramuscular inoculation with ASFV strain ‘Estonia 2014’ resulted in the detection of ASFV genomes in the semen as early as 2 dpi, in blood at 1 dpi while semen quality remained largely unaffected. Ultimately, after insemination with extended semen, 7 of 14 gilts were ASFV positive by 7 days post insemination, and all gilts were ASFV positive by 35 days post insemination. Twelve out of 13 pregnant gilts aborted or resorbed at the onset of fever. A proportion of fetuses originating from the remaining gilt showed both abnormalities and replication of ASFV in fetal tissues. Thus, we present evidence for the efficient transmission of ASFV to gilts via AI and also to implanted embryos. These results underline the critical role that boar semen could play in ASFV transmission.
Immunopathology of Renal Tissue in Fatal Cases of Dengue in Children
Authors: de Lima Siqueira Oliveira Lucca , de Andrade Vieira Alves Felipe , Rabelo Kíssila , Moragas Leandro Junqueira , Mohana-Borges Ronaldo , de Carvalho Jorge José , Basílio-de-Oliveira Carlos , Basílio-de-Oliveira Rodrigo , Rosman Fernando Colonna , Salomão Natália Gedeão , Paes Marciano Viana
Published: December 2022

Dengue virus (DENV) infection represents a worldwide public health concern and can cause damage to multiple organs, including the kidney. In this work, we investigated the histopathological changes caused by dengue virus infection along with the detection of inflammatory mediators, cytokines, and cell expression patterns in the renal tissue of three fatal cases in children. Hematoxylin and Eosin staining was performed to analyze these histopathological changes. Immunohistochemistry allowed for the detection of immunological inflammatory markers in renal tissues that were quantified and further analyzed. Vascular congestion, edema and glomerular infiltrate were observed in the three cases, in addition to the thickening of the matrix area around the glomerular capillaries and mononuclear infiltrate associated with vascular congestion in the medullary region. The renal tissues exhibited collagen deposition and high expression of CD68+ Mø, CD8+ T, CD56+ cells and MMP-9, and the cytokine profile was mainly characterized by the expression of IFN-γ and TNF-α. Additionally, the expression of RANTES, VEGFR-2 and VCAM-1 were observed. The replication of DENV was evidenced by the detection of the NS3 protein. These results contributed to clarifying the main factors that may be involved in changes in the renal tissue of fatal cases of dengue in children.
Protective Effects of Naringin–Dextrin Nanoformula against Chemically Induced Hepatocellular Carcinoma in Wistar Rats: Roles of Oxidative Stress, Inflammation, Cell Apoptosis, and Proliferation
Authors: Mohamed Eman E. , Ahmed Osama M. , Abdel-Moneim Adel , Zoheir Khairy M. A. , Elesawy Basem H. , Al Askary Ahmad , Hassaballa Ahmed , El-Shahawy Ahmed A. G.
Published: December 2022

Nanotechnology holds great promise for the development of treatments for deadly human diseases, such as hepatocellular carcinoma (HCC). In the current study, we compared the hepatoprotective effects of naringin–dextrin nanoparticles (NDNPs) against HCC in male Wistar rats with those of pure naringin and investigated the underlying cellular and molecular mechanisms. HCC was induced by intraperitoneal injection of diethylnitrosamine (DEN, 150 mg/kg body weight (b.w.) per week) for two weeks, followed by oral administration of 2-acetylaminofluorene (2AAF, 20 mg/kg b.w.) four times per week for three weeks. DEN/2AAF-administered rats were divided into three groups that respectively received 1% carboxymethyl cellulose (as vehicle), 10 mg/kg b.w. naringin, or 10 mg/kg b.w. NDNP every other day by oral gavage for 24 weeks. Both naringin and NDNP significantly attenuated the harmful effects of DEN on liver function. Both compounds also suppressed tumorigenesis as indicated by the reduced serum concentrations of liver tumor markers, and this antitumor effect was confirmed by histopathological evaluation. Additionally, naringin and NDNP prevented DEN-induced changes in hepatic oxidative stress and antioxidant activities. In addition, naringin and NDNP suppressed inflammation induced by DEN. Moreover, naringin and NDNP significantly reduced the hepatic expression of Bcl-2 and increased Bax, p53, and PDCD5 expressions. Naringin and NDNP also reduced expression of IQGAP1, IQGAP3, Ras signaling, and Ki-67 while increasing expression of IQGAP2. Notably, NDNP more effectively mitigated oxidative stress and inflammatory signaling than free naringin and demonstrated improved antitumor efficacy, suggesting that this nanoformulation improves bioavailability within nascent tumor sites.
Current Pharmacotherapy and Multi-Target Approaches for Alzheimer’s Disease
Authors: Cheong Siew Lee , Tiew Jian Kai , Fong Yi Hang , Leong How Wan , Chan Yew Mun , Chan Zhi Ling , Kong Ethan Wei Jie
Published: December 2022

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by decreased synaptic transmission and cerebral atrophy with appearance of amyloid plaques and neurofibrillary tangles. Cognitive, functional, and behavioral alterations are commonly associated with the disease. Different pathophysiological pathways of AD have been proposed, some of which interact and influence one another. Current treatment for AD mainly involves the use of therapeutic agents to alleviate the symptoms in AD patients. The conventional single-target treatment approaches do not often cause the desired effect in the disease due to its multifactorial origin. Thus, multi-target strategies have since been undertaken, which aim to simultaneously target multiple targets involved in the development of AD. In this review, we provide an overview of the pathogenesis of AD and the current drug therapies for the disease. Additionally, rationales of the multi-target approaches and examples of multi-target drugs with pharmacological actions against AD are also discussed.
Identification of Potential Treatments for Acute Lymphoblastic Leukemia through Integrated Genomic Network Analysis
Authors: Zazuli Zulfan , Irham Lalu Muhammad , Adikusuma Wirawan , Sari Nur Melani
Published: December 2022

The advancement of high-throughput sequencing and genomic analysis revealed that acute lymphoblastic leukemia (ALL) is a genetically heterogeneous disease. The abundance of such genetic data in ALL can also be utilized to identify potential targets for drug discovery and even drug repurposing. We aimed to determine potential genes for drug development and further guide the identification of candidate drugs repurposed for treating ALL through integrated genomic network analysis. Genetic variants associated with ALL were retrieved from the GWAS Catalog. We further applied a genomic-driven drug repurposing approach based on the six functional annotations to prioritize crucial biological ALL-related genes based on the scoring system. Lastly, we identified the potential drugs in which the mechanisms overlapped with the therapeutic targets and prioritized the candidate drugs using Connectivity Map (CMap) analysis. Forty-two genes were considered biological ALL-risk genes with ARID5B topping the list. Based on potentially druggable genes that we identified, palbociclib, sirolimus, and tacrolimus were under clinical trial for ALL. Additionally, chlorprothixene, sirolimus, dihydroergocristine, papaverine, and tamoxifen are the top five drug repositioning candidates for ALL according to the CMap score with dasatinib as a comparator. In conclusion, this study determines the practicability and the potential of integrated genomic network analysis in driving drug discovery in ALL.
Characterization of Sigma-2 Receptor—Specific Binding Sites Using [3H]DTG and [125I]RHM-4
Authors: Weng Chi-Chang , Riad Aladdin , Lieberman Brian P. , Xu Kuiying , Peng Xin , Mikitsh John L. , Mach Robert H.
Published: December 2022

The sigma-2 receptor/transmembrane protein 97 (σ2R/TMRM97) is a promising biomarker of tumor proliferation and a target for cancer therapy. [3H]DTG has been used to evaluate σ2R/TMEM97 binding affinity in compound development studies. However, [3H]DTG has equal and moderate binding affinities to both sigma 1 receptor (σ1R) and σ2R/TMEM97. Furthermore, co-administration with the σ1R masking compound (+)-pentazocine may cause bias in σ2R/TMEM97 binding affinity screening experiments. We have developed a radioiodinated ligand, [125I]RHM-4, which has high affinity and selectivity for σ2R/TMEM97 versus σ1R. In this study, a head-to-head comparison between [3H]DTG and [125I]RHM-4 on the binding affinity and their effectiveness in σ2R/TMEM97 compound screening studies was performed. The goal of these studies was to determine if this radioiodinated ligand is a suitable replacement for [3H]DTG for screening new σ2R/TMEM97 compounds. Furthermore, to delineate the binding properties of [125I]RHM-4 to the σ2R/TMEM97, the structure of RHM-4 was split into two fragments. This resulted in the identification of two binding regions in the σ2R, the “DTG” binding site, which is responsible for binding to the σ2R/TMEM97, and the secondary binding site, which is responsible for high affinity and selectivity for the σ2R/TMEM97 versus the σ1R. The results of this study indicate that [125I]RHM-4 is an improved radioligand for in vitro binding studies of the σ2R/TMEM97 versus [3H]DTG.
Non-Apoptotic Programmed Cell Death in Thyroid Diseases
Authors: Ji Feihong , Qiu Xinguang
Published: December 2022

Thyroid disorders are among the most common endocrinological conditions. As the prevalence of thyroid diseases increases annually, the exploration of thyroid disease mechanisms and the development of treatments are also gradually improving. With the gradual advancement of therapies, non-apoptotic programmed cell death (NAPCD) has immense potential in inflammatory and neoplastic diseases. Autophagy, pyroptosis, ferroptosis, and immunogenic cell death are all classical NAPCD. In this paper, we have compiled the recent mechanistic investigations of thyroid diseases and established the considerable progress by NAPCD in thyroid diseases. Furthermore, we have elucidated the role of various types of NAPCD in different thyroid disorders. This will help us to better understand the pathophysiology of thyroid-related disorders and identify new targets and mechanisms of drug resistance, which may facilitate the development of novel diagnostic and therapeutic strategies for patients with thyroid diseases. Here, we have reviewed the advances in the role of NAPCD in the occurrence, progression, and prognosis of thyroid diseases, and highlighted future research prospects in this area.
Safety Investigations of Two Formulations for Vaginal Use Obtained from Eugenia uniflora L. Leaves in Female Rats
Authors: Donadel Guilherme , Dalmagro Mariana , de Oliveira João Antonio Berta , Zardeto Giuliana , Pinc Mariana Moraes , Hoscheid Jaqueline , Alberton Odair , Belettini Salviano Tramontin , Jacomassi Ezilda , Gasparotto Junior Arquimedes , Lourenço Emerson Luiz Botelho
Published: December 2022

Medicinal plants have great prominence in research into the development of new medicines. Eugenia uniflora L. (Myrtaceae) is an edible and medicinal plant with economic value in the northeast region of Brazil. Several preparations from E. uniflora leaves and its fruits are employed as a source of nutrients and bioactive compounds. In this study we evaluated the preclinical toxicology of crude extract and vaginal gel obtained from the leaves of E. uniflora (5%, 10%, and 15%) aiming to provide safety for its use in the treatment of vulvovaginitis. Both formulations were applied to the vaginal cavity for 14 days. Detailed observations of the vaginal region, including pruritus, swelling, irritation, burning, pain, and vaginal secretion, as well as the estrous cycle were evaluated. On the fifth day, blood samples were obtained from the supraorbital plexus for biochemical and hematological analyses. The animals were subsequently euthanized. All animals underwent necropsy and macroscopic examination of the vaginal mucosa and reproductive system. A histological examination was also performed. No clinically significant changes were detected during the entire experimental period. All biochemical, hematological, or histopathological parameters were within the normal range for the species. The data obtained allow us to suggest that the E. uniflora vaginal formulations are safe in this experimental model.
Isotopic Radiolabeling of Crizotinib with Fluorine-18 for In Vivo Pet Imaging
Authors: Sardana Malvika , Breuil Louise , Goutal Sébastien , Goislard Maud , Kondrashov Mikhail , Marchal Etienne , Besson Florent L. , Dugave Christophe , Wrigley Gail , Jonson Anna C. , Kuhnast Bertrand , Schou Magnus , Tournier Nicolas , Elmore Charles S. , Caillé Fabien
Published: December 2022

Crizotinib is a tyrosine kinase inhibitor approved for the treatment of non-small-cell lung cancer, but it is inefficient on brain metastases. Crizotinib is a substrate of the P-glycoprotein, and non-invasive nuclear imaging can be used to assess the brain penetration of crizotinib. Positron emission tomography (PET) imaging using fluorine-18-labeled crizotinib would be a powerful tool for investigating new strategies to enhance the brain distribution of crizotinib. We have synthesized a spirocyclic hypervalent iodine precursor for the isotopic labeling of crizotinib in a 2.4% yield. Because crizotinib is an enantiomerically pure drug, a chiral separation was performed to afford the (R)-precursor. A two-step radiolabeling process was optimized and automated using the racemic precursor to afford [18F](R,S)-crizotinib in 15 ± 2 radiochemical yield and 103 ± 18 GBq/µmol molar activity. The same radiolabeling process was applied to the (R)-precursor to afford [18F](R)-crizotinib with comparable results. As a proof-of-concept, PET was realized in a single non-human primate to demonstrate the feasibility of [18F](R)-crizotinib in in vivo imaging. Whole-body PET highlighted the elimination routes of crizotinib with negligible penetration in the brain (SUVmean = 0.1). This proof-of-concept paves the way for further studies using [18F](R)-crizotinib to enhance its brain penetration depending on the P-glycoprotein function.
Dinuclear Iron Complexes of Iminopyridine-Based Ligands as Selective Cytotoxins for Tumor Cells and Inhibitors of Cancer Cell Migration
Authors: Castro Jessica , Bravo Marlon , Albertí Meritxell , Marsal Anaís , Alonso-De Gennaro María José , Martínez-Ferraté Oriol , Claver Carmen , van Leeuwen Piet W. N. M. , Romero Isabel , Benito Antoni , Vilanova Maria
Published: December 2022

A family of dinuclear iron (II) compounds with iminopyridine-based ligands displays selective cytotoxic activity against cancer cell lines. All compounds have IC50 values 2–6 fold lower than that of cisplatin, and 30–90 fold lower than that of carboplatin for the tumor cell lines assayed. Comparing the IC50 values between tumor and non-tumor cell lines, the selectivity indexes range from 3.2 to 34, compound 10, [Fe2(4)2(CH3CN)4](BF4)4, showing the highest selectivity. Those compounds carrying substituents on the iminopyridine ring show the same cytotoxicity as those without substituents. However, the electronic effects of the substituents on position 6 may be important for the cytotoxicity of the complexes, and consequently for their selectivity. All compounds act over DNA, promoting cuts on both strands in the presence of reactive oxygen species. Since compound 10 presented the highest selectivity, its cytotoxic effect was further characterized. It induces apoptosis, affects cell cycle phase distribution in a cell-dependent manner, and its cytotoxic effect is linked to reactive oxygen species generation. In addition, it decreases tumor cell migration, showing potential antimetastatic effects. These properties make compound 10 a good lead antitumor agent among all compounds studied here.
Solid Lipid Microparticles by Spray Congealing of Water/Oil Emulsion: An Effective/Versatile Loading Strategy for a Highly Soluble Drug
Authors: Candiani Alessandro , Milanesi Andrea , Foglio Bonda Andrea , Diana Giada , Bari Elia , Segale Lorena , Torre Maria Luisa , Giovannelli Lorella
Published: December 2022

Spray congealing technique was exploited to produce solid lipid microparticles (SLMp) loaded with a highly water-soluble drug (metoclopramide hydrochloride) dissolved in the aqueous phase of a water in oil (W/O) emulsion. The use of an emulsion as starting material for a spray congealing treatment is not so frequent. Moreover, for this application, a W/O emulsion with a drug dissolved in water is a totally novel path. A ternary diagram was built to optimize the emulsion composition, a factorial design was used to identify the factors affecting the properties of the microparticles and a Design of Experiment strategy was applied to define the impact of process conditions and formulation variables on the SLMp properties. SLMp were characterized by particle size distribution, morphology, residual moisture, drug content, release behavior, FT-IR analysis and XRPD. The obtained microparticles presented a spherical shape, particle size distribution between 54–98 µm depending on atomizing pressure used during the production step and 2–5% residual moisture 4 days after the preparation. XRPD analysis revealed that lipid polymorphic transition alfa-beta occurs depending on the presence of water. In vitro drug release tests highlighted that all the formulations had a reduced release rate compared to the drug alone. These results suggest that spray congealing of a W/O emulsion could be proposed as a good strategy to obtain SLMp with a high loading of a hydrophilic drug and able to control its release rate.
Hélène Cixous, Laida Lertxundi, and the Fruits of the Feminine
Authors: Staab Laura
Published: December 2022

In the fields of experimental writing and experimental filmmaking, respectively, Hélène Cixous and Laida Lertxundi gather images of fruits: apples, oranges and lemons. Although Cixous and Lertxundi are well-known for seeking something of the feminine for writing and filmmaking, in these texts and these films, fruit is not equivalent to feminine anatomy and the juiciness of neither apple, nor orange, nor lemon is mere metaphor for feminine jouissance. While Cixous and Lertxundi recognise in art, literature and philosophy an historical relation of women to nature, an essentialist equation of one to the other is loosened as the texts and the films situate apples, oranges and lemons as organic things in the world. Neither Cixous nor Lertxundi, then, eradicate the distance between human and non-human on the ground of the feminine: fruit is not entwined with women—but women do look, from time to time, at fruit. As if photosynthetically towards the sun, both Cixous and Lertxundi turn from the self towards the world, taken by the beauty and the light of fruit. In an addition to recent ecofeminist philosophy (Donna Haraway, Luce Irigaray) and also to recent feminist film-philosophy on attention (by way of Iris Murdoch, Simone Weil), I refer throughout the article to Kaja Silverman’s philosophy of ‘world spectatorship’ (2000) as I outline the way Cixous and Lertxundi each post-deconstructively combine a language of desire—feminine appetite, curiosity and pleasure—with a language of things to affirm, with women’s eyes on a simple piece of fruit, the world anew.
Influence of Gold Nanoantennas on the Photoluminescence of Silicon Nanocrystals
Authors: Köthemann Ronja , Golla Christian , Qu Hong , Meier Cedrik
Published: December 2022

We study the influence of gold nanoantennas on the photoluminescence signal of silicon nanocrystals. Unlike bulk silicon, which only exhibits low photoluminescence at room temperature due to its indirect band gap, silicon nanocrystals have the advantage of producing strong and size-dependent photoluminescence. Here, we place gold nanoantennas on a layered system in which silicon nanocrystals are integrated. The nanoantennas are embedded in the layered system by subsequent overgrowth. We find that the photoluminescence signal can be manipulated ranging from attenuation to enhancement. Moreover, we investigate the impact of grating coupling and the number of antennas per antenna array on the amplification of the photoluminescence signal.
Impact of Temperature on Phenolic and Osmolyte Contents in In Vitro Cultures and Micropropagated Plants of Two Mediterranean Plant Species, Lavandula viridis and Thymus lotocephalus
Authors: Mansinhos Inês , Gonçalves Sandra , Rodríguez-Solana Raquel , Ordóñez-Díaz José Luis , Moreno-Rojas José Manuel , Romano Anabela
Published: December 2022

In this study, in vitro cultures and micropropagated plants of two Mediterranean aromatic plants, Lavandula viridis L’Hér and Thymus lotocephalus López and Morales, were exposed to different temperatures (15, 20, 25, and 30 °C). The effect of temperature on the levels of hydrogen peroxide (H2O2), lipid peroxidation, and osmoprotectants (proline, soluble sugars, and soluble proteins), as well as on the phenolic profile by HPLC-HRMS and intermediates of the secondary metabolism (phenylalanine ammonia lyase (PAL) activity and shikimic acid content), was investigated. Moreover, the antioxidant activity of the plant extracts was also analyzed. Overall, considering the lipid peroxidation and H2O2 content, the extreme temperatures (15 and 30 °C) caused the greatest damage to both species, but the osmoprotectant response was different depending on the species and plant material. In both species, phenolic compounds and related antioxidant activity increased with the rise in temperature in the micropropagated plants, while the opposite occurred in in vitro cultures. L. viridis cultures showed the highest biosynthesis of rosmarinic acid (92.6 g/kgDW) at 15 °C and seem to be a good alternative to produce this valuable compound. We conclude that contrasting temperatures greatly influence both species’ primary and secondary metabolism, but the response is different depending on the plant micropropagation stage.
Morphological, Biochemical, and Molecular Diversity of an Indian Ex Situ Collection of Pomegranate (Punica granatum L.)
Authors: Parashuram Shilpa , Singh Nripendra Vikram , Gaikwad Nilesh Nivrutti , Corrado Giandomenico , Roopa Sowjanya P. , Basile Boris , Devaraja Nitesh Shirur , Chandra Ram , Babu Karuppannan Dhinesh , Patil Prakash Goudappa , Kumar Pradeep , Singh Akath , Marathe Rajiv Arvind
Published: December 2022

Pomegranate (Punica granatum, L.) is a fruit tree that is increasingly popular worldwide due to the health-related properties of the fruit juice. While several studies highlighted the rich phytochemical diversity, few efforts have been devoted to an integrative understanding of the level of diversity of this species. This study investigated the diversity of 40 pomegranate accessions in an Indian ex situ collection by using twenty-nine morphological traits, six biochemical parameters, and twenty-nine Simple Sequence Repeats (SSR) markers. Among the evaluated traits, fruit volume (23.34% CV), fruit weight (21.12% CV), and fruit color (*a) (22.69 % CV) largely contributed to the morphological classification. Based on Mahalanobis D2 distance and Tocher’s clustering, the 40 pomegranate accessions were grouped into eight clusters, partly consistent with their origin. Specifically, cultivars introduced from foreign countries were present in distinct clusters. The SSR marker analysis generated 66 alleles. The observed heterozygosity values ranged from 0.05 to 0.63, with a mean value of 0.30. Maximum molecular genetic dissimilarity was observed between ‘IC-318720′ and ‘Gul-e-Shah Red’ (0.30). The neighbor-joining dendrogram separated wild accessions from cultivated varieties. The combination of morphological, biochemical, and molecular characterization allowed for comprehensively characterizing the pomegranate diversity and provided information on the relationships between the different aspects of the diversity. This work also suggests that the origin of the accessions is an important factor of discrimination and that the level of admixture between local and foreign material is currently limited.