bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Cucurbiturils on the Production of Reactive Oxygen Species by T- and B-Lymphocytes, Platelets and Red Blood Cells
Authors: Aktanova Alina A. , Boeva Olga S. , Barkovskaya Margarita Sh. , Kovalenko Ekaterina A. , Pashkina Ekaterina A.
Published: January 2023

Reactive oxygen species (ROS) are highly reactive chemical molecules containing oxygen. ROS play an important role in signaling and cell homeostasis at low and moderate concentrations. ROS could be a cause of damage to proteins, nucleic acids, lipids, membranes and organelles at high concentrations. There are a lot of cells that can produce ROS to maintain functional activity. It is known that metal nanoparticles can increase production of ROS in cells. However, the effect of cucurbiturils on ROS production is still unknown. In our study, we evaluated production of ROS by the immune (T-, B-lymphocytes, NK-cells) and non-immune cells (red blood cells, platelets), as well as tumor cells line (1301, K562) after treatment with cucurbiturils in vitro. Assessment of reactive oxide species (ROS) were provided by using dihydrorhodamine 123 (DHR 123). Fluorescence intensity and percentage DHR123 were measured by flow cytometry. Platelets, erythrocytes and activated T-helpers were changed the level of ROS production in response to stimulation with cucurbiturils. It was found that the percentage of these ROS-producing cells was reduced by cucurbiturils. Thus, cucurbiturils may affect the production of ROS by cells, but further research is needed in this area.
Tumorigenicity of EGFR- and/or HER2-Positive Breast Cancers Is Mediated by Recruitment of Tumor-Associated Macrophages
Authors: You Daeun , Kim Hyungjoo , Jeong Yisun , Yoon Sun Young , Lo Eunji , Kim Sangmin , Lee Jeong Eon
Published: January 2023

Basal-like breast cancer (BLBC) has a clinically aggressive nature. It is prevalent in young women and is known to often relapse rapidly. To date, the molecular mechanisms regarding the aggressiveness of BLBC have not been fully understood. In the present study, mechanisms of aggressiveness of BLBC involving EGFR and/or HER2 expression and interactions between tumor and tumor-associated macrophages (TAMs) were explored. The prognosis of breast cancer patients who underwent surgery at Samsung Medical Center was analyzed. It was found that the co-expression of EGFR and HER2 was associated with a worse prognosis. Therefore, we generated EGFR-positive BLBC cells with stable HER2 overexpression and analyzed the profile of secretory cytokines. Chemokine (C-C motif) ligand 2 (CCL2) expression was increased in HER2-overexpressed BLBC cells. Recombinant human CCL2 treatment augmented the motility of TAMs. In addition, the conditioned culture media of HER2-overexpressed BLBC cells increased the motility of TAMs. Furthermore, activation of TAMs by CCL2 or the conditioned culture media of HER2-overexpressed cells resulted in the production of pro-inflammatory cytokines, such as IL-8 and IL-1β. These observations reveal that CCL2 derived from EGFR and HER2 co-expressed BLBC cells can lead to increased TAM recruitment and the induction of IL-8 and IL-1β from recruited TAMs, triggering the tumorigenesis of breast cancer with the expression of both EGFR and HER2. Our findings demonstrate that EGFR+ and HER2+ BLBC aggressiveness is partially mediated through the interaction between BLBC and TAMs recruited by CCL2.
Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins
Authors: Vovk Andrei , Zilman Anton
Published: January 2023

Intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) perform diverse functions in cellular organization, transport and signaling. Unlike the well-defined structures of the classical natively folded proteins, IDPs and IDRs dynamically span large conformational and structural ensembles. This dynamic disorder impedes the study of the relationship between the amino acid sequences of the IDPs and their spatial structures and dynamics, with different experimental techniques often offering seemingly contradictory results. Although experimental and theoretical evidence indicates that some IDP properties can be understood based on their average biophysical properties and amino acid composition, other aspects of IDP function are dictated by the specifics of the amino acid sequence. We investigate the effects of several key variables on the dimensions and the dynamics of IDPs using coarse-grained polymer models. We focus on the sequence “patchiness” informed by the sequence and biophysical properties of different classes of IDPs—and in particular FG nucleoporins of the nuclear pore complex (NPC). We show that the sequence composition and patterning are well reflected in the global conformational variables such as the radius of gyration and hydrodynamic radius, while the end-to-end distance and dynamics are highly sequence-specific. We find that in good solvent conditions highly heterogeneous sequences of IDPs can be well mapped onto averaged minimal polymer models for the purpose of prediction of the IDPs dimensions and dynamic relaxation times. The coarse-grained simulations are in a good agreement with the results of atomistic MD. We discuss the implications of these results for the interpretation of the recent experimental measurements, and for the further applications of mesoscopic models of FG nucleoporins and IDPs more broadly.
Vertical Transmission and Antifungal Susceptibility Profile of Yeast Isolates from the Oral Cavity, Gut, and Breastmilk of Mother–Child Pairs in Early Life
Authors: Azevedo Maria João , Araujo Ricardo , Campos Joana , Campos Carla , Ferreira Ana Filipa , Falcão-Pires Inês , Ramalho Carla , Zaura Egija , Pinto Eugénia , Sampaio-Maia Benedita
Published: January 2023

Yeast acquisition begins at birth; however, the contribution of the mother on yeast transmission to the offspring and associated resistance is yet to be clarified. The aim of this study was to explore the vertical transmission of yeasts and their antifungal susceptibility profile in early life. Oral, fecal, and breastmilk samples were collected from 73 mother–child pairs four to twelve weeks after delivery and cultured on Sabouraud dextrose agar with chloramphenicol. The isolates were identified by MALDI-TOF MS. The vertical transmission was studied by microsatellite genotyping. Antifungal susceptibility was determined for fluconazole, voriconazole, miconazole, anidulafungin, and nystatin by broth microdilution assay, following CLSI–M60 guidelines. A total of 129 isolates were identified from 53% mother–child pairs. We verified the vertical transmission of Candida albicans (n = three mother–child pairs) and Candida parapsilosis (n = one mother–child pair) strains, including an antifungal resistant strain transmitted from breastmilk to the gut of a child. Most isolates were susceptible to the tested antifungals, with the exception of four C. albicans isolates and one R. mucilaginosa isolate. The vertical transmission of yeasts happens in early life. This is the first work that demonstrated the role of the mother as a source of transmission of antifungal-resistant yeasts to the child.
Discovery of Tryptanthrin and Its Derivatives and Its Activities against NSCLC In Vitro via Both Apoptosis and Autophagy Pathways
Authors: Zou Yayu , Zhang Guanglong , Li Chengpeng , Long Haitao , Chen Danping , Li Zhurui , Ouyang Guiping , Zhang Wenjing , Zhang Yi , Wang Zhenchao
Published: January 2023

In this study, a series of novel tryptanthrin derivatives were synthesized and their inhibitory activities against selected human cancer cell lines, namely, lung (A549), chronic myeloid leukemia (K562), prostate (PC3), and live (HepG2), were evaluated using a methyl thiazolyl tetrazolium colorimetric (MTT) assay. Among the tested compounds, compound C1 exhibited a promising inhibitory effect on the A549 cell line with an IC50 value of 0.55 ± 0.33 µM. The observation of the cell morphological result showed that treatment with C1 could significantly inhibit the migration of A549 cells through the cell migration assay. Moreover, after treatment with C1, the A549 cells exhibited a typical apoptotic morphology and obvious autophagy. In addition, the detection of apoptosis and the mitochondrial membrane potential indicated that C1 induced A549 cell apoptosis via modulating the levels of Bcl2 family members and disrupted the mitochondrial membrane potential. Compound C1 also suppressed the expression of cyclin D1 and increased the expression of p21 in the A549 cells, inducing cell cycle arrest in the G2/M phase in a dose dependent manner. The further mechanism study found that C1 markedly increased the transformation from LC3-I to LC3-II. Taken together, our results suggest that C1 is capable of inhibiting the proliferation of non-small cell lung cancer (NSCLC) cells, inducing cell apoptosis, and triggering autophagy.
The Monocytic Cell Line THP-1 as a Validated and Robust Surrogate Model for Human Dendritic Cells
Authors: Hölken Johanna Maria , Teusch Nicole
Published: January 2023

We have implemented an improved, cost-effective, and highly reproducible protocol for a simple and rapid differentiation of the human leukemia monocytic cell line THP-1 into surrogates for immature dendritic cells (iDCs) or mature dendritic cells (mDCs). The successful differentiation of THP-1 cells into iDCs was determined by high numbers of cells expressing the DC activation markers CD54 (88%) and CD86 (61%), and the absence of the maturation marker CD83. The THP-1-derived mDCs are characterized by high numbers of cells expressing CD54 (99%), CD86 (73%), and the phagocytosis marker CD11b (49%) and, in contrast to THP-1-derived iDCs, CD83 (35%) and the migration marker CXCR4 (70%). Treatment of iDCs with sensitizers, such as NiSO4 and DNCB, led to high expression of CD54 (97%/98%; GMFI, 3.0/3.2-fold induction) and CD86 (64%/96%; GMFI, 4.3/3.2-fold induction) compared to undifferentiated sensitizer-treated THP-1 (CD54, 98%/98%; CD86, 55%/96%). Thus, our iDCs are highly suitable for toxicological studies identifying potential sensitizing or inflammatory compounds. Furthermore, the expression of CD11b, CD83, and CXCR4 on our iDC and mDC surrogates could allow studies investigating the molecular mechanisms of dendritic cell maturation, phagocytosis, migration, and their use as therapeutic targets in various disorders, such as sensitization, inflammation, and cancer.
Concentration of Polycyclic Aromatic Hydrocarbons (PAHs) in Human Serum and Adipose Tissues and Stimulatory Effect of Naphthalene in Adipogenesis in 3T3-L1 Cells
Authors: Mlyczyńska Ewa , Bongrani Alice , Rame Christelle , Węgiel Małgorzata , Maślanka Anna , Major Piotr , Zarzycki Piotr , Ducluzeau Pierre-Henri , De Luca Arnaud , Bourbao-Tournois Celine , Froment Pascal , Rak Agnieszka , Dupont Joëlle
Published: January 2023

Polycyclic aromatic hydrocarbons (PAHs) are one of the most prevalent classes of environmental pollutants. Some evidence shows that PAHs could be involved in human obesity. However, little is known about the distribution patterns of PAHs in human adipose tissue (AT) and the role of PAHs on adipogenesis/lipogenesis. The aims of this pilot study were to determine concentrations of 16 PAHs defined as high-priority pollutants in the plasma and adipose tissue of French and Polish bariatric patients, as well as their correlation with body mass index (BMI), plasma and AT adipokines expression levels. We finally investigated the role of naphthalene on cell proliferation, viability, and differentiation in 3T3-L1 preadipocytes. The concentration of most PAHs was similar in the three types of AT and it was significantly higher in AT as compared to plasma, suggesting bioaccumulation. Polish patients had higher PAH levels in AT than French ones. Only the concentration of naphthalene in AT was positively correlated with the BMI and serum or adipose chemerin, adiponectin and resistin expression, in French but not in Polish patients, who had significantly higher BMIs. Moreover, naphthalene exposure increased the cell proliferation of 3T3-L1 preadipocytes and lipogenesis, and increased the expression of genes involved in adipogenesis after cell differentiation. Taken together, PAHs and more particularly naphthalene could be an obesogenic molecule and increase the risk of obesity.
Dry Eye Disease: What Is the Role of Vitamin D?
Authors: Rolando Maurizio , Barabino Stefano
Published: January 2023

Dry eye disease (DED) is a multifactorial condition resulting from reduced tear secretion from the lacrimal glands, increased tear water evaporation or the production of poor-quality tears. Such tear instability can lead to inflammation and damage of the ocular surface, as well as to abnormal nociception. Historically, tear substitutes and corticosteroids have been the bastion of DED therapy, but a substantial number of patients still suffer from residual symptoms even after being treated with traditional treatments. Aiming to find safe and effective alternative therapies, recent efforts have been focused on the role of vitamin D in the cellular physiology of the eye. Possibly because of its positive effect in modulating the immune and inflammatory responses, the systemic supplementation of vitamin D seems, indeed, to be an effective therapeutic strategy, especially, but not only, for patients affected by DED that does not respond to conventional treatments. In this context, this review focuses on the literature reporting on the pathogenesis and treatment of DED, with a special emphasis on the recent investigations reporting on the potential role of the systemic administration of vitamin D as a therapeutic approach in the management of such condition.
Optimized Antimicrobial Peptide Jelleine-I Derivative Br-J-I Inhibits Fusobacterium Nucleatum to Suppress Colorectal Cancer Progression
Authors: Jia Fengjing , Yu Qun , Wang Ruolei , Zhao Ling , Yuan Fuwen , Guo Haidong , Shen Yunhui , He Feng
Published: January 2023

Colorectal cancer (CRC) is a major health burden worldwide due to its high morbidity, mortality, and complex etiology. Fusobacterium nucleatum (Fn), a Gram-negative anaerobe found in 30% of CRC patients, promotes CRC carcinogenesis, metastasis, and chemoresistance. Effective antimicrobial treatment is an unmet need for the rising CRC burden. Antimicrobial peptides (AMPs) represent a new class of antimicrobial drugs. In our previous study, we did the structure-activity study of Jelleine-I (J-I) and identified several halogenated J-I derivatives Cl-J-I, Br-J-I, and I-J-I. To determine whether those J-I derivatives can be a new therapy for bacterial-associated CRC, here we tested the antibacterial activities of these AMPs against Fn and their effects on CRC development. We found that Br-J-I showed the highest anti-Fn activity and Br-J-I may target membrane-associated FadA for Fn membrane disruption. More importantly, Fn promoted the growth of CRC cells-derived xenograft tumors. Br-J-I suppressed Fn load, colon inflammation, and Fn-induced CRC growth. Of note, Br-J-I induced better anti-CRC effects than common antibiotic metronidazole and Br-J-I sensitized the cancer-killing effect of chemotherapy drug 5-fluorouracil. These results suggest that Br-J-I could be considered as an adjunctive agent for CRC treatment and AMPs-based combination treatment is a new strategy for CRC in the future.
Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer
Authors: Yoon Ji Hye , Kim Mi-Yeon , Cho Jae Youl
Published: January 2023

The skin is the main barrier between the body and the environment, protecting it from external oxidative stress induced by ultraviolet rays. It also prevents the entrance of infectious agents such as viruses, external antigens, allergens, and bacteria into our bodies. An overreaction to these agents causes severe skin diseases, including atopic dermatitis, pruritus, psoriasis, skin cancer, and vitiligo. Members of the flavonoid family include apigenin, quercetin, luteolin, and kaempferol. Of these, apigenin has been used as a dietary supplement due to its various biological activities and has been shown to reduce skin inflammation by downregulating various inflammatory markers and molecular targets. In this review, we deal with current knowledge about inflammatory reactions in the skin and the molecular mechanisms by which apigenin reduces skin inflammation.
Protective Efficacy of Anti-Hyr1p Monoclonal Antibody against Systemic Candidiasis Due to Multi-Drug-Resistant Candida auris
Authors: Singh Shakti , Barbarino Ashley , Youssef Eman G. , Coleman Declan , Gebremariam Teclegiorgis , Ibrahim Ashraf S.
Published: January 2023

Candida auris is a multi-drug-resistant fungal pathogen that can survive outside the host and can easily spread and colonize the healthcare environment, medical devices, and human skin. C. auris causes serious life-threatening infections (up to 60% mortality) in immunosuppressed patients staying in such contaminated healthcare facilities. Some isolates of C. auris are resistant to virtually all clinically available antifungal drugs. Therefore, alternative therapeutic approaches are urgently needed. Using in silico protein modeling and analysis, we identified a highly immunogenic and surface-exposed epitope that is conserved between C. albicans hyphal-regulated protein (Cal-Hyr1p) and Hyr1p/Iff-like proteins in C. auris (Cau-HILp). We generated monoclonal antibodies (MAb) against this Cal-Hyr1p epitope, which recognized several clinical isolates of C. auris representing all four clades. An anti-Hyr1p MAb prevented biofilm formation and enhanced opsonophagocytic killing of C. auris by macrophages. When tested for in vivo efficacy, anti-Hyr1p MAb protected 55% of mice against lethal systemic C. auris infection and showed significantly less fungal burden. Our study is highly clinically relevant and provides an effective alternative therapeutic option to treat infections due to MDR C. auris.
Can a Negative Representation of Refugees in Social Media Lead to Compassion Fatigue? An Analysis of the Perspectives of a Sample of Syrian Refugees in Jordan and Turkey
Authors: Aldamen Yasmin
Published: January 2023

Negative, tragic, traumatic and suffering representations continue to dominate the discussions and content on social media in the stories and content related to Syrian refugees. The public, while browsing social media, finds that this representation is the dominant one that dominates the image of refugees. Thus, there is a potential risk that the public’s compassion will be negatively affected after repeated exposure to the dominant representation in light of the inability to put an end to that situation. This study discusses the perspectives of Syrian refugees living in Jordan and Turkey on whether they feel such repeated negative and tragic content about their stories and news on social media could affect the empathy of the audience in hosting communities with them, especially since social media is an open-source platform that all people at any time and from any place can post, re-share, comment and create content by adding texts, photos and videos, not like traditional media, which are controlled more than social media platforms for open participatory content. This study aims to explore how a vulnerable population, such as Syrian refugees in Istanbul and Amman, sees the effect of negative representation on themselves and their image in the hosting communities and does not aim to examine or offer any conclusion as to whether the public in Jordan and Turkey have experienced compassion fatigue. This study provides and extracts some useful insights, but proves no hypotheses or conclusive evidence regarding the occurrence of compassion fatigue in the public; thus, the study opens the door for the debate on the role that social media plays as a source of compassion fatigue among citizens towards refugees, mainly when they are repeatedly exposed to such negative stories and content, as well as calls for an in-depth and extensive study on the topic from the point of view of the public and citizens in the hosting countries, after examining, understanding and analyzing the opinions and their dimensions of the sample of refugees in this study.
Acetaminophen-Induced Hepatotoxicity in Obesity and Nonalcoholic Fatty Liver Disease: A Critical Review
Authors: Begriche Karima , Penhoat Clémence , Bernabeu-Gentey Pénélope , Massart Julie , Fromenty Bernard
Published: January 2023

The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.
A Comparative Study on the Clinical Efficacy of Simple Transobturator Midurethal Sling and Posterior Pelvic Floor Reconstruction
Authors: Tian Daoming , Gao Zhenhua , Zhou Hang , Lin Han , Wang Xingqi , Li Ling , Yang Xunguo , Wen Yubin , Zhang Quan , Shen Jihong
Published: January 2023

Background and Objectives: The purpose of this study was to compare the complications, success rate and satisfaction of pelvic floor reconstruction after transobturator midurethral sling (TOT) and TOT combined with pelvic floor reconstruction in the treatment of female stress urinary incontinence. To explore the pathogenesis of stress urinary incontinence after pelvic floor stress injury and improve the surgical treatment strategy. Materials and Methods: From 15 August 2018 to 24 February 2022, patients diagnosed with stress urinary incontinence (SUI) and secondary prolapse of the anterior pelvis were selected to receive surgically. Participants were followed up and evaluated at 2 months, 6 months and 1 year after treatment. According to the patient’s chief complaint, the patient can urinate automatically without incontinence. The number of urinary incontinence and urine leakage was significantly reduced compared with those before operation. Urinary incontinence symptoms did not improve or worsen as ineffective, observing the efficacy and complications. Results: We included 191 patients in the TOT group and 151 patients in the pelvic floor reconstruction group after TOT was combined. The operation time and hospital stay in the TOT group were short, but the TOT group needed a second operation to treat recurrent SUI. Perioperative complications were mostly dysuria, and the incidence of postoperative complications in the group of TOT combined with pelvic floor reconstruction was low. The complete success rate and effective rate of pelvic floor reconstruction after TOT in the merger group were significantly higher than those in the TOT group, and the patient satisfaction and complete success rate were also higher. Conclusions: TOT combined with posterior pelvic floor reconstruction has a definite short-term effect on patients with SUI and anterior pelvic secondary prolapse. The operation design should pay attention to the support of the posterior wall of the perineum to the bladder neck and the middle and proximal end of the urethra.
Nutrition Situation Analysis in the UAE: A Review Study
Authors: Al Sabbah Haleama , Assaf Enas A. , Al-Jawaldeh Ayoub , AlSammach Afra Salah , Madi Haifa , Khamis Al Ali Nouf , Al Dhaheri Ayesha S. , Cheikh Ismail Leila
Published: January 2023

This review study aimed to assess the nutrition situation in the UAE using published data from 2010 to 2022. It highlights the gaps and challenges that prevail in addressing the nutrition-related problems in the UAE and the opportunities that have been overlooked. The available literature indicates that the UAE is burdened with more than one form of nutrition-related problems, including being underweight, being overweight, obesity, micronutrient deficiencies, and nutrition-related chronic diseases. It is clear that data on micronutrient deficiencies, protein-energy malnutrition, obesity, diabetes, and other nutrition-related diseases among the UAE population are extremely scarce. The UAE has a high prevalence of obesity and diabetes; however, limited studies have been conducted to document this nutritional phenomenon. Few examples of published data are available assessing the burden of stunting, wasting, and being underweight among children under five years of age. Despite the importance of protein-energy malnutrition, no recent publications analyze its prevalence within the UAE population. Therefore, future studies must be conducted, focusing on malnutrition. Based on the literature, and bearing in mind the magnitude of the health issues due to the UAE population’s nutrition negligence, there is an urgent need to assess the population’s nutrient behaviors, to aid policy decision-makers in developing and implementing effective health policies and strategies.
Adherence to a Mediterranean Diet for 6 Months Improves the Dietary Inflammatory Index in a Western Population: Results from the MedLey Study
Authors: Clark Jessie S. , Dyer Kathryn A. , Davis Courtney R. , Shivappa Nitin , Hébert James R. , Woodman Richard , Hodgson Jonathan M. , Murphy Karen J.
Published: January 2023

Increasing evidence supports that a higher dietary inflammatory index (DII®) score is associated with inflammation and cardiovascular disease (CVD) risk, events, and mortality. This randomized trial sought to determine if a change to a Mediterranean diet resulted in a reduction in the DII score, and then it evaluated the relationship between the DII and cardiometabolic outcomes following the administration of a traditional Mediterranean diet in older Australian adults. A total of 152 Australian adults (mean age 71 ± 5 years) was randomly allocated either a MedDiet (n = 80) or to continue their habitual diet (HabDiet) (n = 72) for 6 months. Diet and cardiovascular outcomes were measured at baseline and 3 and 6 months of the intervention. DII and energy-adjusted DII (E-DIITM) scores were calculated from 3-day weighed food records. There was a significant reduction in the DII score at 2 and 4 months for the MedDiet group (−1.40 ± 0.20 p < 0.001 and −1.47 ± 0.20 p < 0.001, respectively), which was significantly different from the HabDiet group over time (p < 0.001). The HabDiet DII score did not change significantly at the 2 and 4 months timepoints (0.47 ± 0.21 p = 0.35 and 0.54 ± 0.21 p = 0.21, respectively). The improvement in the DII in the MedDiet group was not related to any cardiometabolic outcome. Baseline cross-sectional analyses identified a positive association between the E-DII score and average BMI, body weight, WHR, abdominal adiposity, and SBP, and a negative association with HDL-C. We demonstrate that a MedDiet intervention significantly reduced DII scores compared with a habitual Australian diet in older Australians. This could be beneficial for healthy ageing and the avoidance of chronic disease in Western populations.
Herbal Honey Preparations of Curcuma Xanthorriza and Black Cumin Protect against Carcinogenesis through Antioxidant and Immunomodulatory Activities in Sprague Dawley (SD) Rats Induced with Dimethylbenz(a)anthracene
Authors: Hidayati Titiek , Indrayanti Indrayanti , Darmawan Endang , Akrom Akrom
Published: January 2023

Background: Traditionally, Curcuma xanthorriza (CX), black cumin seed (BC), and honey have been used by the Indonesian people as medicinal ingredients to treat various health symptoms. CX extracts and BC have been proven in the laboratory as chemopreventive agents, antioxidants, and immunomodulators. In this study, we developed CX extract, BC oil, and honey into herbal honey preparations (CXBCH) and hypothesized that the preparations show chemopreventive activity. The purpose of the study was to determine the CXBCH potential as chemopreventive, antioxidant, and immunomodulatory. Method: In this experimental laboratory research, antioxidant, immunomodulatory, and cytotoxic activities were tested on human mammary cancer cell lines (T47D cells) while the chemopreventive activity of the CXBCH preparations on Sprague Dawley (SD) rats induced with dimethylbenzene(a)anthracene (DMBA). Results: CXBCH preparations demonstrated immunomodulatory, antioxidant, and cytotoxic activities in T47D, Hela, and HTB-183 cells and in DMBA-induced SD rats, as the preparations inhibited tumor nodule formation, increased the number of CD4, CD8 and CD4CD25 cells, and glutathione-S-transferase (GST) activity, and decreased serum NO levels. Conclusions: CXBCH preparations display chemopreventive, antioxidant, and immunomodulatory properties.
Abdominal Fat Characteristics and Mortality in Rectal Cancer: A Retrospective Study
Authors: Pellegrini Massimo , Besutti Giulia , Ottone Marta , Canovi Simone , Bonelli Efrem , Venturelli Francesco , Farì Roberto , Damato Angela , Bonelli Candida , Pinto Carmine , Ligabue Guido , Pattacini Pierpaolo , Giorgi Rossi Paolo , El Ghoch Marwan
Published: January 2023

The aim of this study was to evaluate the association of adipose tissue characteristics with survival in rectal cancer patients. All consecutive patients, diagnosed with stage II–IV rectal cancer between 2010–2016 using baseline unenhanced Computed Tomography (CT), were included. Baseline total, subcutaneous and visceral adipose tissue areas (TAT, SAT, VAT) and densities (TATd, SATd, VATd) at third lumbar vertebra (L3) were retrospectively measured. The association of these tissues with cancer-specific and progression-free survival (CCS, PFS) was assessed by using competitive risk models adjusted by age, sex and stage. Among the 274 included patients (median age 70 years, 41.2% females), the protective effect of increasing adipose tissue area on survival could be due to random fluctuations (e.g., sub-distribution hazard ratio—SHR for one cm2 increase in SAT = 0.997; 95%confidence interval—CI = 0.994–1.000; p = 0.057, for CSS), while increasing density was associated with poorer survival (e.g., SHR for one Hounsfield Unit—HU increase in SATd = 1.03, 95% CI = 1.01–1.05, p = 0.002, for CSS). In models considering each adipose tissue area and respective density, the association with CSS tended to disappear for areas, while it did not change for TATd and SATd. No association was found with PFS. In conclusion, adipose tissue density influenced survival in rectal cancer patients, raising awareness on a routinely measurable variable that requires more research efforts.
Prevalence of Radiological Chronic Pancreatitis and Exocrine Pancreatic Insufficiency in Patients with Decompensated Liver Disease: Is Fecal Elastase Useful in This Setting?
Authors: Llibre-Nieto Gemma , Lira Alba , Vergara Mercedes , Casas Meritxell , Solé Cristina , Ferrusquía-Acosta José , Puig-Diví Valentí , Grau-López Laia , Barradas Josep Maria , Solà Marta , Miquel Mireia , Sánchez-Delgado Jordi
Published: January 2023

Chronic alcohol consumption is a well-known etiological factor for both chronic pancreatitis (CP) and liver cirrhosis. However, there is discussion over how often these two entities are present together in the same patient. The main goal of our study is to establish the prevalence of CP and low fecal elastase (FE-1) in patients with decompensated liver disease (DLD). In addition, we aim to identify the demographic, epidemiological and clinical factors associated with EPI and CP in patients with decompensated liver cirrhosis. This was an observational single-center study including 119 consecutive patients hospitalized for acute decompensation of cirrhosis, mostly of alcoholic etiology. Patients underwent computed tomography (CT) or magnetic resonance imaging (MRI) to assess the radiological features of CP. We also performed two FE-1 tests and complete blood tests to assess the presence of exocrine pancreatic insufficiency (EPI) and nutritional status, including micronutrients. The results of our study show that 32 patients (26.9%) had low fecal elastase suggesting EPI and 11 (9.2%) had CP. Patients meeting radiological CP criteria had lower FE-1 than patients without CP. There were no statistically significant differences in micronutrient deficiencies according to the presence of CP or not. Likewise, we did not find any statistically significant differences in micronutrient deficiencies among patients with normal and low FE-1 indicative of EPI. FE-1 alone may not be suitable for assessing EPI in patients with acute DLD. Detecting co-existing pancreatic disease may be important in a subset of patients with DLD, when the FE-1 levels are significantly low, potentially suggestive of a pancreatic anomaly. Moreover, the clinical manifestations of EPI and CP are not useful in detecting CP in DLD patients. Likewise, CP cannot explain all causes of EPI in these patients.
The Effect of the Extra Virgin Olive Oil Minor Phenolic Compound 3′,4′-Dihydroxyphenylglycol in Experimental Diabetic Kidney Disease
Authors: Rodriguez-Pérez María Dolores , Santiago-Corral Laura , Ortega-Hombrados Laura , Verdugo Cristina , Arrebola María Monsalud , Martín-Aurioles Esther , Fernández-Prior María África , Bermúdez-Oria Alejandra , De La Cruz José Pedro , González-Correa José Antonio
Published: January 2023

The aim of this study was to analyze the possible nephroprotective effect of 3’,4’-dihydroxyphenylglycol (DHPG), a polyphenolic compound of extra virgin olive oil (EVOO), on renal lesions in an experimental model of type 1 diabetes. Rats were distributed as follows: healthy normoglycemic rats (NDR), diabetic rats treated with saline (DR), and DR treated with 0.5 mg/kg/day or 1 mg/kg/day of DHPG. DR showed a significantly higher serum and renal oxidative and nitrosative stress profile than NDR, as well as reduced prostacyclin production and renal damage (defined as urinary protein excretion, reduced creatinine clearance, increased glomerular volume, and increased glomerulosclerosis index). DHPG reduced the oxidative and nitrosative stress and increased prostacyclin production (a 59.2% reduction in DR and 34.7–7.8% reduction in DHPG-treated rats), as well as 38–56% reduction in urinary protein excretion and 22–46% reduction in glomerular morphological parameters (after the treatment with 0.5 or 1 mg/kg/day, respectively). Conclusions: DHPG administration to type 1-like diabetic rats exerts a nephroprotective effect probably due to the sum of its antioxidant (Pearson’s coefficient 0.68–0.74), antinitrosative (Pearson’s coefficient 0.83), and prostacyclin production regulator (Pearson’s coefficient 0.75) effects.
Ultra-Processed Food Consumption Is Related to Higher Trans Fatty Acids, Sugar Intake, and Micronutrient-Impaired Status in Schoolchildren of Bahia, Brazil
Authors: Menezes Camilla Almeida , Magalhães Letícia Bastos , da Silva Jacqueline Tereza , da Silva Lago Renata Maria Rabello , Gomes Alexvon Nunes , Ladeia Ana Marice Teixeira , Vianna Nelzair Araújo , Oliveira Ricardo Riccio
Published: January 2023

Ultra-processed food (UPF) consumption impacts nutrient intake and plays an important role in non-communicable diseases (NCD), even among schoolchildren. This cross-sectional study aimed to characterize the food consumption of this population and its relationship with laboratory and anthropometric aspects. A sample of 190 subjects aged 5 to 19 y was randomly selected for dietary, laboratory, and anthropometric assessment. Statistical inference was calculated using Spearman’s correlation. Excess weight was observed in 34%, a high Waist-to-Height Ratio in 9%, and hypertriglyceridemia in 17% of the subjects, higher among those from urban schools (45%, p = 0.011; 15%, p = 0.015; 24%, p = 0.026, respectively). UPF consumption represented 21% of caloric intake and showed a positive correlation with trans fatty acids (r = 0.70) and sugar (r = 0.59) intake. Unprocessed food consumption showed a weak, but significant, correlation with Body Mass Index (r = 0.22) and Waist Circumference (r = 0.23), while processed meat showed a negative correlation with serum ferritin (r = −0.16) and vitamins D (r = −0.20) and B12 (r = −0.15). These findings highlight the need for public policies to promote Food and Nutritional Security for schoolchildren to prevent NCD and nutritional deficiencies.
Dietary Intake, Serum Hormone Concentrations, Amenorrhea and Bone Mineral Density of Physique Athletes and Active Gym Enthusiasts
Authors: Mursu Jaakko , Ristimäki Maija , Malinen Inga , Petäjä Pirita , Isola Ville , Ahtiainen Juha P. , Hulmi Juha J.
Published: January 2023

As the diet, hormones, amenorrhea, and bone mineral density (BMD) of physique athletes (PA) and gym enthusiasts (GE) are little-explored, we studied those in 69 females (50 PA, 19 GE) and 20 males (11 PA, 9 GE). Energy availability (EA, kcal·kgFFM−1·d−1 in DXA) in female and male PA was ~41.3 and ~37.2, and in GE ~39.4 and ~35.3, respectively. Low EA (LEA) was found in 10% and 26% of female PA and GE, respectively, and in 11% of male GE. In PA, daily protein intake (g/kg body mass) was ~2.9–3.0, whereas carbohydrate and fat intakes were ~3.6–4.3 and ~0.8–1.0, respectively. PA had higher protein and carbohydrate and lower fat intakes than GE (p < 0.05). Estradiol, testosterone, IGF-1, insulin, leptin, TSH, T4, T3, cortisol, or BMD did not differ between PA and GE. Serum IGF-1 and leptin were explained 6% and 7%, respectively, by EA. In non-users of hormonal contraceptives, amenorrhea was found only in PA (27%) and was associated with lower fat percentage, but not EA, BMD, or hormones. In conclusion, off-season dietary intakes, hormone levels, and BMD meet the recommendations in most of the PA and GE. Maintaining too-low body fat during the off-season may predispose to menstrual disturbances.
Evaluation of a Plant-Based Infant Formula Containing Almonds and Buckwheat on Gut Microbiota Composition, Intestine Morphology, Metabolic and Immune Markers in a Neonatal Piglet Model
Authors: Gurung Manoj , Rosa Fernanda , Yelvington Brooke , Terry Nathan , Read Quentin D. , Piccolo Brian D. , Moody Becky , Tripp Patricia , Pittman Hoy E. , Fay Bobby L. , Ross Talyor J. , Sikes James D. , Flowers Jessica B. , Fox Renee , LeRoith Tanya , Talatala Rachelanne , Bar-Yoseph Fabiana , Yeruva Laxmi
Published: January 2023

A controlled-neonatal piglet trial was conducted to evaluate the impact of a plant-based infant formula containing buckwheat and almonds as the main source of protein compared to a commercially available dairy-based formula on the gut health parameters. Two day old piglets were fed either a plant-based or a dairy-based formula until day 21. Gut microbiome, cytokines, growth and metabolism related outcomes, and intestinal morphology were evaluated to determine the safety of the plant-based infant formula. This study reported that the plant-based formula-fed piglets had a similar intestinal microbiota composition relative to the dairy-based formula-fed group. However, differential abundance of specific microbiota species was detected within each diet group in the small and large intestinal regions and fecal samples. Lactobacillus delbrueckii, Lactobacillus crispatus, and Fusobacterium sp. had higher abundance in the small intestine of plant-based formula-fed piglets compared to the dairy-based group. Bacteroides nordii, Enterococcus sp., Lactobacillus crispatus, Prevotella sp., Ruminococcus lactaris, Bacteroides nordii, Eisenbergiella sp., Lactobacillus crispatus, Prevotella sp., and Akkermansia muciniphila had greater abundance in the large intestine of the plant based diet fed piglets relative to the dairy-based diet group. In the feces, Clostridiales, Bacteroides uniformis, Butyricimonasvirosa, Cloacibacillus porcorum, Clostridium clostridioforme, and Fusobacterium sp. were abundant in dairy-based group relative to the plant-based group. Lachnospiraceae, Clostridium scindens, Lactobacillus coleohominis, and Prevetolla sp. had greater abundance in the feces of the plant-based group in comparison to the dairy-based group. Gut morphology was similar between the plant and the dairy-based formula-fed piglets. Circulatory cytokines, magnesium, triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), vitamin D, vitamin K, and IgE levels were similar among all piglets independent of dietary group. Overall, the present study demonstrated that a plant-based formula with buckwheat and almonds as the primary source of protein can support similar gut microbiota growth and health outcomes compared to a dairy-based infant formula.
Soy Food Consumption Is Inversely Associated with Handgrip Strength: Results from the TCLSIH Cohort Study
Authors: Wu Hongmei , Quan Jing , Wang Xuena , Gu Yeqing , Zhang Shunming , Meng Ge , Zhang Qing , Liu Li , Wang Xing , Sun Shaomei , Jia Qiyu , Song Kun , Huang Jian , Huo Junsheng , Zhang Bing , Ding Gangqiang , Niu Kaijun
Published: January 2023

Background: Soy foods contain high levels of soy protein or isoflavones, which can stimulate muscle protein synthesis and increase antioxidant capacity, and thus ameliorate muscle strength decline. However, data from epidemiological studies investigating the association of habitual soy food consumption with muscle strength decline among general Chinese adults are limited. Methods: This study included 29,525 participants (mean age: 41.6 years; 16,933 (53.8%) males). Soy food consumption was evaluated using a validated 100-item food frequency questionnaire. Handgrip strength (HGS) was assessed with a hand dynamometer. Analysis of covariance were performed to assess the multivariable-adjusted least square means (LSM) and 95% confidence interval (CI) for HGS. Results: The multiple adjusted LSM (95% CI) of HGS across soy food consumption were 35.5 (34.2, 37.1) kg for <1 time per week, 36.1 (34.6, 37.6) kg for 1 time per week, 36.3 (34.8, 37.8) kg for 2–3 times per week, and 36.6 (35.1, 38.0) kg for ≥4 times per week (p for trend < 0.001). Compared to participants with soy food consumption less than one time per week, the multiple adjusted odds ratio (95% CI) of low HGS was 0.638 (0.485, 0.836) when the weekly consumption was ≥ 4 times (p for trend < 0.01). Conclusions: Higher habitual soy food consumption was positively associated with HGS in general Chinese adults. Consumption of soy foods may have beneficial effects on muscle health.
Amber Extract Suppressed Mast Cell-Mediated Allergic Inflammation via the Regulation of Allergic Mediators—An In Vitro Study
Authors: Refli Redoyan , Sofyana Neng Tanty , Haeiwa Haruna , Takeda Reiko , Okazaki Kazuma , Sekita Marie , Sakamoto Kazuichi
Published: January 2023

The various clinical approaches for treating allergy-related diseases have shown modest progress in low side effects and improved clinical outcomes. Therefore, finding alternative anti-allergic agents is crucial. The present study explored the anti-allergic effects of amber extract (fossilized tree resin) in RBL-2H3 mast cells stimulated with different allergens. In order to support the information on the inflammatory effect of the amber extract, NO production analysis on RAW 264.7 cells was conducted. β-Hexosaminidase release, an indicator of the efficacy of the amber extract in preventing mast cell activation and degranulation, reactive oxygen species (ROS) generation, and the effect of the amber extract on key cytokines production on RBL-2H3 cells, was evaluated. The results demonstrated that amber extract at concentrations up to 50 μg/mL had no cytotoxic effect on RAW 264.7 and RBL-2H3 cells. Amber extract inhibited NO production in RAW 264.7 cells. Treatment with amber extract significantly suppressed the release of β-hexosaminidase, especially at 50 μg/mL. Furthermore, amber extract suppressed the significantly increased ROS levels induced by allergen stimulation and allergy-associated cytokines. The results also suggested that amber extract exerts anti-allergic inflammatory effects by inhibiting the MAPK and NF-κB signaling pathways, resulting in decreased cytokines production. Thus, the amber extract is a promising anti-allergic agent.
Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies
Authors: Kozalak Gül , Bütün İsmail , Toyran Erçil , Koşar Ali
Published: January 2023

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic has been developed for various reasons. 2D cell cultures and animal models have failed to understand the MM disease and Bortezomib resistance. It is therefore essential to utilize new technologies to reveal a complete molecular profile of the disease. In this review, we in-depth examined the possible molecular mechanisms that cause Bortezomib resistance and specifically addressed MM and Bortezomib resistance. Moreover, we also included the use of nanoparticles, 3D culture methods, microfluidics, and organ-on-chip devices in multiple myeloma. We also discussed whether the emerging technology offers the necessary tools to understand and prevent Bortezomib resistance in multiple myeloma. Despite the ongoing research activities on MM, the related studies cannot provide a complete summary of MM. Nanoparticle and 3D culturing have been frequently used to understand MM disease and Bortezomib resistance. However, the number of microfluidic devices for this application is insufficient. By combining siRNA/miRNA technologies with microfluidic devices, a complete molecular genetic profile of MM disease could be revealed. Microfluidic chips should be used clinically in personal therapy and point-of-care applications. At least with Bortezomib microneedles, it could be ensured that MM patients can go through the treatment process more painlessly. This way, MM can be switched to the curable cancer type list, and Bortezomib can be targeted for its treatment with fewer side effects.
Development and Characterization of Novel In-Situ-Forming Oleogels
Authors: Dümichen Anne , Lucas Henrike , Trutschel Marie-Luise , Mäder Karsten
Published: January 2023

PLGA-based in situ forming implants (ISFI) often require a high amount of potentially toxic solvents such as N methyl-Pyrrolidone (NMP). The aim of the present study was to develop lipid in-situ-forming oleogels (ISFOs) as alternative delivery systems. 12-Hydroxystearic acid (12-HSA) was selected as the oleogelling agent and three different oleoformulations were investigated: (a) 12-HSA, peanut oil (PO), NMP; (b) 12-HSA, medium-chain triglycerides (MCT), ethanol; (c) 12-HSA, isopropyl myristate (IPM), ethanol. The effects of the 12-HSA concentration, preparation method, and composition on the mechanical stability were examined using a texture analysis and oscillating rheology. The texture analysis was used to obtain information on the compression strength. The amplitude sweeps were analyzed to provide information on the gel strength and the risk of brittle fractures. The frequency sweeps allowed insights into the long-term stability and risk of syneresis. The syringeability of the ISFOs was tested, along with their acute and long-term cytotoxicity in vitro. The developed ISFOs have the following advantages: (1) the avoidance of highly acidic degradation products; (2) low amounts of organic solvents required; (3) low toxicity; (4) low injection forces, even with small needle sizes. Therefore, ISFOs are promising alternatives to the existing polymer/NMP-based ISFIs.