bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Implications of the Bidirectional Relationship between the Gut Microflora and Inflammatory Diseases with Special Emphasis on Irritable Bowel Disease: Current and Future Perspective
Authors: Aziz Tariq , Khan Ayaz Ali , Tzora Athina , Voidarou Chrysoula (Chrysa) , Skoufos Ioannis
Published: June 2023

The immune system is vital for safeguarding the human body against infections and inflammatory diseases. The role of diet and meal patterns in modulating immune function is complex, and highlighting this topic is crucial for identifying potential ways to improve immune health. In Europe, the Mediterranean diet and Western diet are the most common dietary patterns, and gaining an understanding of how they affect immune function is essential for public health. There are numerous inflammatory diseases that are observed in younger and older people. Some of the common diseases include polymyalgia rheumatica (PMR), spinal muscular atrophy (SMA), vasculitis, sarcopenia, cirrhosis, cancer, and fibromyalgia, but the main focus in this review article is on irritable bowel disease (IBD). In general, dietary choices can have an immense impact on the microbial flora of the gut in people with inflammatory diseases. The intake of Mediterranean-style foods promotes the growth of healthy bacteria that enhances the function of the immune system. On the other hand, it is mostly seen that the intake of Western-style foods leads to the growth of harmful gut bacteria that contributes to inflammation and disease development by weakening the immune system. Additionally, inflammation in the gut can impact brain function, leading to mood disorders, such as anxiety and depression. Rare inflammatory diseases, such as psoriasis and sarcoidosis, are of main interest in this article. All the above-mentioned common and rare inflammatory diseases have a certain relationship with the microbiota of the gut. The gut microbiome plays a significant role in IBD; fiber and prebiotic interventions may represent promising adjunct therapies for pediatric IBD by targeting the gut microbiome. By advancing a good overall arrangement of microorganisms in the stomach through dietary mediations, working on the side effects and alleviating of diseases might be conceivable. The gut microbiota can be affected differently by various dietary fatty acid types. There is also an involvement of genetics in the progression of IBD, such as transcriptional factors, and one gene of interest is the LCT gene, which encodes for lactase, an enzyme responsible for digesting lactose in the gut.
Sourdough “Biga” Fermentation Improves the Digestibility of Pizza Pinsa Romana: An Investigation through a Simulated Static In Vitro Model
Authors: Costantini Alice , Verni Michela , Mastrolonardo Federica , Rizzello Carlo Giuseppe , Di Cagno Raffaella , Gobbetti Marco , Breedveld Mario , Bruggink Suzan , Lefever Kristof , Polo Andrea
Published: June 2023

Baked goods manufacturing parameters and fermentation conditions interfere with the nutrients content and affect their gastrointestinal fate. Pinsa Romana is a type of pizza that, recently, has been commercially rediscovered and that needed elucidation from a nutritional and digestibility perspective. In this study, six types of Pinsa Romana (five made with indirect method and one produced with straight dough technology) were characterized for their biochemical and nutritional features. Several variables like indirect (biga) Pinsa Romana production process, fermentation time and use of sourdough were investigated. The Pinsa Romana made with biga including sourdough and fermented for 48 h at 16 °C ((PR_48(SD)) resulted in the lowest predicted glycemic index, in the highest content of total peptides, total and individual free amino acids and gamma-amino butyric acid (GABA), and in the best protein quality indexes (protein efficiency ratio and nutritional index). The static in vitro digestion showed that the digesta from PR_48(SD) confirmed a reduced in vitro glycemic response after intake, and it showed a lower bioavailability of hydrophilic peptides. Furthermore, the inclusion of sourdough in biga enhanced the bioavailability of protein-related end-products including human health promoting compounds such as essential amino acids.
Formononetin, a Beer Polyphenol with Catabolic Effects on Chondrocytes
Authors: Guillán-Fresco María , Franco-Trepat Eloi , Alonso-Pérez Ana , Jorge-Mora Alberto , López-López Verónica , Pazos-Pérez Andrés , Piñeiro-Ramil María , Gómez Rodolfo
Published: June 2023

Beer consumption has been identified as a risk factor for osteoarthritis (OA), a rheumatic disease characterised by cartilage degradation, joint inflammation, and eventual joint failure. One of the main isoflavonoids in beer is formononetin (FNT), an estrogenic compound also found in multiple plants and herbs. In this study, we aimed to investigate the effect of FNT on chondrocyte viability, inflammation, and metabolism. Cells were treated with FNT with or without IL-1β for 48 h and during 7 days of differentiation. Cell viability was determined via MTT assay. Nitrite accumulation was determined by Griess reaction. The expression of genes involved in inflammation and metabolism was determined by RT-PCR. The results revealed that a low concentration of FNT had no deleterious effect on cell viability and decreased the expression of inflammation-related genes. However, our results suggest that FNT overexposure negatively impacts on chondrocytes by promoting catabolic responses. Finally, these effects were not mediated by estrogen receptors (ERs) or aryl hydrocarbon receptor (AhR). In conclusion, factors that favour FNT accumulation, such as long exposure times or metabolic disorders, can promote chondrocyte catabolism. These data may partially explain why beer consumption increases the risk of OA.
Functional Properties of Natural Products and Human Health
Authors: Bontempo Paola , De Masi Luigi , Rigano Daniela
Published: June 2023

Natural products (NPs), broadly defined as chemicals produced by living organisms including microbes, marine organisms, animals, fungi and plants, are widely used as therapeutic agents for treating diseases and maintaining health and “wellness” [...]
Editorial to the Special Issue ‘Nutritional Intervention in Digestive Diseases in the Era of Nutraceuticals, Nutrigenomics and Microbiomics’
Authors: Ashktorab Hassan , Brim Hassan
Published: June 2023

Environmental exposures, particularly diet, play an important role in the prevention or exacerbation of illnesses, including gastrointestinal (GI) diseases [...]
Endometriosis Treatment: Role of Natural Polyphenols as Anti-Inflammatory Agents
Authors: Tassinari Valentina , Smeriglio Antonella , Stillittano Virgilio , Trombetta Domenico , Zilli Romano , Tassinari Roberta , Maranghi Francesca , Frank Giulia , Marcoccia Daniele , Di Renzo Laura
Published: June 2023

Endometriosis is an estrogen-dependent common chronic inflammatory disease defined by the presence of extrauterine endometrial tissue that promotes pelvic pain and fertility impairment. Its etiology is complex and multifactorial, and several not completely understood theories have been proposed to describe its pathogenesis. Indeed, this disease affects women’s quality of life and their reproductive system. Conventional therapies for endometriosis treatment primarily focus on surgical resection, lowering systemic levels of estrogen, and treatment with non-steroidal anti-inflammatory drugs to counteract the inflammatory response. However, although these strategies have shown to be effective, they also show considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis; however, to date, only very limited literature is present on this topic. Polyphenols display important anti-endometriotic properties; in particular, they are potent phytoestrogens that in parallel modulates estrogen activity and exerts anti-inflammatory activity. The aim of this review is to provide an overview on anti-inflammatory activity of polyphenols in the treatment of endometriosis.
Dietary Vitamin D Intake in Italian Subjects: Validation of a Frequency Food Questionnaire (FFQ)
Authors: Nuti Ranuccio , Gennari Luigi , Cavati Guido , Pirrotta Filippo , Gonnelli Stefano , Caffarelli Carla , Tei Luciano , Merlotti Daniela
Published: June 2023

Vitamin D plays a crucial role in calcium and phosphate metabolism, relating to bone health and preventing metabolic bone disorders such as rickets and osteomalacia. Vitamin D deficiency (serum 25-OH-D values <20 ng/mL or 50 nmol/L) is common also in Italian people; it is recommended to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. Supplementation and/or fortification with either ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) aimed to modify this condition have commonly been proposed. Studies about vitamin D intake are numerous in the literature but not adequately designed and are very often incomplete in Mediterranean Countries such as in the Italian population. On these bases, we performed a survey to validate a frequency food questionnaire (FFQ) specifically created to rapidly assess dietary vitamin D intake in Italian people. For this aim, the data of questionnaires were compared with results derived in the same population from a designed 14-day frequency food diary (FFD). Overall, a good correlation between FFQ and FFD was observed (r = 0.89, p < 0.001), both demonstrating a remarkably low vitamin D intake, irrespective of age and gender. Our data confirm that the vitamin D intake is very low in Italy, which likely contributes to hypovitaminosis D.
Maternal Pre-Pregnancy BMI, Offspring Adiposity in Late Childhood, and Age of Weaning: A Causal Mediation Analysis
Authors: Zhang Jie , Clayton Gemma L. , Hansen Stefan Nygaard , Olsen Anja , Lawlor Deborah A. , Dahm Christina C.
Published: June 2023

Infant feeding practices have been hypothesized to influence offspring’s body mass index (BMI) later in life, and women with overweight or obesity tend to wean their infants earlier than women with healthy BMI. We, therefore, aimed to investigate how much early age of weaning mediated the maternal-offspring adiposity relationship. The study included 4920 mother-child pairs from the Avon Longitudinal Study of Parents and Children birth cohort. G-computation was applied to estimate the natural direct (NDE) and indirect (NIE) effects, via the age of weaning (<3 months, 3 months, >3 months), of maternal pre-pregnancy overweight or obesity on offspring’s BMI and fat mass index. The NDE of maternal overweight or obesity on offspring BMI at 17 years old was 2.63 kg/m2 (95% CI: 2.27 to 2.99). The NIE via the age of weaning was 0.02 kg/m2 (95% CI: 0.00 to 0.04), corresponding to 0.8% of the total effect. Similar results were observed for the offspring’s fat mass index. The NDE and NIE were similar to the main analyses when we looked at the relationship stratified by breastfeeding status. Our study found a minimal influence of age of weaning on the pathway between maternal and offspring adiposity, indicating the age of weaning may not be a key mediator.
Efficacy and Safety of a Parenteral Nutrition Program for Patients with RAS Wild-Type Metastatic Colorectal Cancer Administered First-Line Cetuximab Plus Chemotherapy: A Propensity Score Matching Study
Authors: Chang Yu-Tang , Chen Chou-Chen , Chang Shih-Ching , Chang Yu-Yao , Lin Bo-Wen , Chen Hong-Hwa , Hsieh Yao-Yu , Hsu Hung-Chih , Hsieh Meng-Che , Kuan Feng-Che , Wu Chih-Chien , Lu Wei-Chen , Su Yu-Li , Liang Yi-Hsin , Chen Joe-Bin , Huang Shuan-Yuan , Huang Ching-Wen , Wang Jaw-Yuan
Published: June 2023

Malnutrition is a common problem in patients with metastatic colorectal cancer (mCRC) receiving targeted therapy plus chemotherapy, resulting in severe toxicity and decreased survival rates. This retrospective study employing propensity score matching (PSM) examined the efficacy and safety of a supplemental home parenteral nutrition (HPN) program for patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy. This retrospective nationwide registry study included data from 14 medical centers/hospitals across Taiwan, and the data period ranged from November 2016 to December 2020. Patients with RAS wild-type mCRC receiving cetuximab plus chemotherapy as their first-line therapy were included and divided into HPN and non-HPN program groups. HPN was initiated based on patient-specific factors, such as baseline nutritional status, treatment-related toxicities, and comorbidities. Clinical outcomes were evaluated using response to therapy, duration of response (DoR), progression-free survival (PFS), and overall survival (OS). This study recruited 758 patients, of whom 110 and 648 were included in the HPN and non-HPN program groups, respectively. After 1:3 PSM, the data of 109 and 327 patients from the HPN and non-HPN program groups were analyzed, respectively. The HPN program group had a higher metastasectomy rate (33.9% vs. 20.2%, p = 0.005), and longer duration of treatment and DoR than the non-HPN program group (13.6 vs. 10.3 and 13.6 vs. 9.9 months, p = 0.001 and < 0.001, respectively). The HPN program group tended to have a longer median PFS (18.2 vs. 13.9 months, p = 0.102). Moreover, we noted a significant improvement in the median OS in the same group (53.4 vs. 34.6 months, p = 0.002). Supplemental HPN programs may be recommended for select patients with mCRC receiving targeted therapy plus chemotherapy to improve oncological outcomes.
Enhanced Measurement of Sugar-Sweetened Beverage Marketing to Young Immigrant Children in Grocery Store Environments
Authors: Dastgerdizad Hadis , Dombrowski Rachael D. , Kulik Noel , Knoff Kathryn A. G. , Bode Bree , Mallare James , Elyaderani Dariush K. , Kaur Ravneet
Published: June 2023

The marketing of Sugar-Sweetened Beverages (SSBs) within grocers is an obesogenic factor that negatively impacts children’s nutritional behavior, specifically for people from racial and ethnic minority groups, such as immigrants. We aimed to develop and employ a methodology that more precisely assesses the availability, price, and promotion of SSBs to young immigrant children within independently owned grocery stores. A case comparison design was used to explore the differences in the grocery store landscape of SSB marketing by conducting an enhanced Nutrition Environment Measures Survey-SSB (NEMS-SSB) within 30 grocery stores in the Hispanic and Latino enclaves in Southwest Detroit, in the Arab and Chaldean enclaves in North-central Detroit, and in Warren, Hamtramck, and Dearborn, in comparison with 48 grocers in Metro Detroit. Unsweetened, plant-based, and organic toddler and infant beverages, as well as questions about marketing, were added to the original NEMS to capture the promotion tactics used in marketing SSBs. NEMS-SSB scores revealed that, in the immigrant enclaves, there was a significantly higher availability of SSBs in grocery stores (−2.38), and they had lower prices than those in the comparison group (−0.052). Unsweetened, plant-based, and organic beverages were unavailable in 97% of all participating grocery stores across both groups. Signage featuring cartoon characters was the most frequent in-store SSB marketing tactic across both groups. Widespread SSB marketing toward toddlers within the grocery stores in immigrant enclaves could be linked with the higher early childhood obesity prevalence among the immigrant population. Our findings can assist local and national organizations in developing and implementing healthy eating interventions. This study must be repeated in other immigrant enclaves across states to provide comparable results.
Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway
Authors: Liu Jie , Mai Peishi , Yang Zihui , Wang Zongwei , Yang Wei , Wang Ziyuan
Published: June 2023

Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H2O2)-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H2O2-induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway.
A Comparison of Clinical and Radiographic Signs of Nontuberculous Mycobacterial Pulmonary Disease, Destructive Drug-Resistant Pulmonary Tuberculosis and a Combination of Nontuberculous Mycobacterium Pulmonary Disease and Pulmonary Tuberculosis
Authors: Giller Dmitrii , Scherbakova Galina , Enilenis Inga , Martel Ivan , Kesaev Oleg , Koroev Vadim , Popova Anna , Ilyukhin Alexandr , Basangova Valeria , Smerdin Sergey , Mayusupov Shokirjon , Saenko Sergey , Frolova Olga , Vinarskaya Veronika , Severova Lyudmila
Published: June 2023

A misdiagnosis of isolated pulmonary tuberculosis (pTB) is highly likely when a patient has nontuberculous mycobacterial pulmonary disease (NTMPD) or a combination of nontuberculous mycobacterium pulmonary disease and pulmonary tuberculosis. Frequently, bacterial excretion is absent or only Mycobacteria tuberculosis (MBT) is found. This often results in an incorrect diagnosis and subsequent misinformed treatment regimes. In order to determine possible clinical and radiographic differences between patients with NTMPD (Group 1), destructive drug-resistant pulmonary tuberculosis (Group 3) and a combination of NTMPD and pTB (Group 2) we compare clinical and radiographic signs for these three patient groups. When comparing with Group 3 (2.5%), Groups 1 (25%) and 2 (17.4%) have a substantially higher incidence of pulmonary haemorrhages. Thus, upon clinically observing the combination of pTB and NTMPD, there are no pathognomonic clinical and radiographic detected symptoms. However, the presence of an indolent course, hemoptysis and bronchiectasis in the presence of acid-fast bacteria (or identified MBT) in the sputum makes it possible to suspect not simple pTB, but a combination of pTB and NTMPD. To clarify this necessitated in-depth bacteriological examination.
The Extraordinary Case of a Woman with a 30-Year-Long Diffuse Leishmaniasis Cured with One Single Ampoule of Intranasal Pentavalent Antimoniate
Authors: Gonçalves Sheila V. C. B. , Costa Dorcas L. , Cantinho-Junior João da J. , Vieira-Junior José N. , Ishikawa Edna A. Y. , Costa Rubens N. , Costa-Filho Antônio C. G. , Araújo Ronald da C. , Uliana Silvia R. B. , Yasunaka Jenicer K. U. Y. , Coelho Adriano C. , Costa Jackson M. L. , Costa Carlos H. N.
Published: June 2023

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.
A 5-Year Study of Antiseizure Medications (ASMs) Monitoring in Patients with Neuropsychiatric Disorders in an Italian Clinical Center
Authors: Biso Letizia , Carli Marco , Kolachalam Shivakumar , Monticelli Giorgio , Calabrò Pasquale Fabio , di Paolo Antonello , Giorgi Filippo Sean , Bocci Guido , Scarselli Marco
Published: June 2023

Despite receiving appropriate antiseizure medications (ASMs), a relevant percentage of neuropsychiatric patients do not benefit from this approach, and one reason is subtherapeutic ASMs plasma concentration (C(p)) due to improper drug adherence, interindividual pharmacokinetic differences, or metabolic interactions among different drugs. For these reasons, therapeutic drug monitoring (TDM) by measuring ASMs C(p) is an effective tool that improves pharmacological therapies in clinical practice. Based on these premises, in the present real-world study, we analyzed the C(p) of the most used ASMs in diverse medical conditions, which were assayed during the years 2018–2022 at the University Hospital of Pisa, including about 24,000 samples. This population was largely heterogeneous, and our database did not contain clinical information about the patients. The most used ASMs were Valproate (VPA: 54.5%) and Levetiracetam (LEV: 18.6%), followed by Oxcarbazepine (OxCBZ: 8.3%) and Carbamazepine (CBZ: 7.2%), whereas the associations LEV/VPA, Ethosuximide (ESM)/VPA, and CBZ/VPA were the most frequently proposed. In about 2/3 of assays, ASMs C(p) was in range, except for VPA, which was underdosed in almost half of the samples. Importantly, toxic levels of ASMs C(p) were found very rarely. For VPA, there was a decrease of mean C(p) across ages, from adolescents to older patients, while the C(p) of LEV, CBZ, OxCBZ, and Topiramate (TPM) showed a slight tendency to increase. When we compared females and males, we found that for VPA, the average age was higher for females, whereas women taking Lamotrigine (LTG) and OxCBZ were younger than men. Then, comparing ASMs used in neurologic and psychiatric disorders, based on the request form, it emerged that the mean C(p) of CBZ, OxCBZ, and LTG on samples collected in the Psychiatric Unit was lower compared to the Neurology and Child Neuropsychiatry Units. Finally, the ASMs subjected to multiple dosing starting from an initial subtherapeutic C(p) increased their level at different time points within a year, reaching the reference range for some of them. In conclusion, the present study suggests that TDM is widely applied to monitor ASMs C(p), finding many of them within the reference range, as a demonstration of its utility in clinical practice.
Application of the Analytical Procedure Lifecycle Concept to a Quantitative 1H NMR Method for Total Dammarane-Type Saponins
Authors: Li Wenzhu , Yang Jiayu , Zhao Fang , Xie Xinyuan , Pan Jianyang , Qu Haibin
Published: June 2023

Dammarane-type saponins (DTSs) exist in various medicinal plants, which are a class of active ingredients with effects on improving myocardial ischemia and immunomodulation. In this study, a quantitative 1H NMR method of total DTSs in herbal medicines was developed based on the analytical procedure lifecycle. In the first stage (analytical procedure design), the Ishikawa diagram and failure mode effects and criticality analysis were used to conduct risk identification and risk ranking. Plackett–Burman design and central composite design were used to screen and optimize critical analytical procedure parameter. Then, the method operable design region was obtained through modeling. In the second stage (analytical procedure performance qualification), the performance of methodological indexes was investigated based on analytical quality by design. As examples of continued procedure performance verification, the method was successfully applied to determine the total DTSs in herbal pharmaceutical preparations and botanical extracts. As a general analytical method to quantify total DTSs in medicinal plants or pharmaceutical preparations, the developed method provides a new quality control strategy for various products containing dammarane-type saponin.
Enteric-Coated Cysteamine Bitartrate in Cystinosis Patients
Authors: Klank Sabrina , van Stein Christina , Grüneberg Marianne , Ottolenghi Chris , Rauwolf Kerstin K. , Grebe Jürgen , Reunert Janine , Harms Erik , Marquardt Thorsten
Published: June 2023

Cystinosis is a severe inherited metabolic storage disease caused by the lysosomal accumulation of cystine. Lifelong therapy with the drug cysteamine bitartrate is necessary. Cysteamine cleaves intralysosomal cystine, and thereafter, it can exit from the organelle. The need for frequent dosing every 6 h and the high prevalence of gastrointestinal side effects lead to poor therapy adherence. The purpose of our study was to improve cysteamine treatment by comparing the efficacy of two cysteamine formulas. This is highly relevant for the long-term outcome of cystinosis patients. The cystine and cysteamine levels of 17 patients taking immediate-release cysteamine (IR-cysteamine/Cystagon®) and 6 patients taking encapsulated delayed-release cysteamine (EC-cysteamine) were analyzed. The EC-cysteamine levels showed a near-ideal pharmacokinetic profile indicative of delayed release (longer Tmax and Tmin), and the corresponding cystine levels showed few fluctuations. In addition, the Cmax of IR-cysteamine was greater, which was responsible for unbearable side effects (e.g., nausea, vomiting, halitosis, lethargy). Treatment with EC-cysteamine improves the quality of life of cystinosis patients because the frequency of intake can be reduced to 2–3 times daily and it has a more favorable pharmacokinetic profile than IR-cysteamine. In particular, cystinosis patients with no access to the only approved delayed-release cysteamine Procysbi® could benefit from a cost-effective alternative.
Correction: Trenkel, M.; Scherließ, R. Nasal Powder Formulations: In-Vitro Characterisation of the Impact of Powders on Nasal Residence Time and Sensory Effects. Pharmaceutics 2021, 13, 385
Authors: Trenkel Marie , Scherließ Regina
Published: June 2023

There was an error in the original publication [...]
Combining Molecular Dynamics Simulations and Biophysical Characterization to Investigate Protein-Specific Excipient Effects on Reteplase during Freeze Drying
Authors: Ko Suk Kyu , Björkengren Gabriella , Berner Carolin , Winter Gerhard , Harris Pernille , Peters Günther H. J.
Published: June 2023

We performed molecular dynamics simulations of Reteplase in the presence of different excipients to study the stabilizing mechanisms and to identify the role of excipients during freeze drying. To simulate the freeze-drying process, we divided the process into five distinct steps: (i) protein–excipient formulations at room temperature, (ii) the ice-growth process, (iii)–(iv) the partially solvated and fully dried formulations, and (v) the reconstitution. Furthermore, coarse-grained (CG) simulations were employed to explore the protein-aggregation process in the presence of arginine. By using a coarse-grained representation, we could observe the collective behavior and interactions between protein molecules during the aggregation process. The CG simulations revealed that the presence of arginine prevented intermolecular interactions of the catalytic domain of Reteplase, thus reducing the aggregation propensity. This suggests that arginine played a stabilizing role by interacting with protein-specific regions. From the freeze-drying simulations, we could identify several protein-specific events: (i) collapse of the domain structure, (ii) recovery of the drying-induced damages during reconstitution, and (iii) stabilization of the local aggregation-prone region via direct interactions with excipients. Complementary to the simulations, we employed nanoDSF, size-exclusion chromatography, and CD spectroscopy to investigate the effect of the freeze-drying process on the protein structure and stability.
Phenylalanine and Tryptophan-Based Surfactants as New Antibacterial Agents: Characterization, Self-Aggregation Properties, and DPPC/Surfactants Vesicles Formulation
Authors: Hafidi Zakaria , Pérez Lourdes , El Achouri Mohammed , Pons Ramon
Published: June 2023

Cationic surfactants based on phenylalanine (CnPC3NH3Cl) and tryptophan (CnTC3NH3Cl) were synthesized using renewable raw materials as starting compounds and a green synthetic procedure. The synthesis, acid-base equilibrium, aggregation properties, and antibacterial activity were investigated. Conductivity and fluorescence were used to establish critical micelle concentrations. Micellization of CnPC3NH3Cl and CnTC3NH3Cl occurred in the ranges of 0.42–16.2 mM and 0.29–4.6 mM, respectively. Since those surfactants have some acidic character, the apparent pKa was determined through titrations, observing increasing acidity with increasing chain length and being slightly more acidic with the phenylalanine than the tryptophan derivatives. Both families showed promising antibacterial efficacy against eight different bacterial strains. Molecular docking studies against the enzyme peptidoglycan glycosyltransferase (PDB ID:2OQO) were used to investigate the potential binding mechanism of target surfactant molecules. According to small angle X-ray scattering (SAXS) results, the surfactants incorporate into DPPC (Dipalmitoyl Phosphatidyl Choline) bilayers without strong perturbation up to high surfactant concentration. Some of the C12TC3NH3Cl/DPPC formulations (40%/60% and 20%/80% molar ratios) exhibited good antibacterial activity, while the others were not effective against the tested bacteria. The strong affinity between DPPC and surfactant molecules, as determined by the DFT (density functional theory) method, could be one of the reasons for the loss of antibacterial activity of these cationic surfactants when they are incorporated in vesicles.
ABA Biosynthesis- and Signaling-Related Gene Expression Differences between Sweet Cherry Fruits Suggest Attenuation of ABA Pathway in Bicolored Cultivars
Authors: Acevedo Orlando , Ponce Claudio , Arellano Macarena , Multari Salvatore , Carrera Esther , Donoso José Manuel , Martens Stefan , Kuhn Nathalie , Meisel Lee A.
Published: June 2023

Fruit development involves exocarp color evolution. However, signals that control this process are still elusive. Differences between dark-red and bicolored sweet cherry cultivars rely on MYB factor gene mutations. Color evolution in bicolored fruits only occurs on the face receiving sunlight, suggesting the perception or response to color-inducing signals is affected. These color differences may be related to synthesis, perception or response to abscisic acid (ABA), a phytohormone responsible for non-climacteric fruit coloring. This work aimed to determine the involvement of ABA in the coloring process of color-contrasting varieties. Several phenolic accumulation patterns differed between bicolored ‘Royal Rainier’ and dark-red ‘Lapins’. Transcript abundance of ABA biosynthetic genes (PavPSY, PavZEP and PavNCED1) decreased dramatically from the Pink to Red stage in ‘Royal Rainier’ but increased in ‘Lapins’, which correlated with a higher ABA content in this dark-red cultivar. Transcripts coding for ABA signaling (PavPP2Cs, PavSnRKs and PavMYB44.1) were almost undetectable at the Red stage in ‘Royal Rainier’. Field trials revealed that ‘Royal Rainier’ color development was insensitive to exogenous ABA, whereas it increased in ‘Lapins’. Furthermore, ABA treatment only increased transcript levels of signaling genes in ‘Lapins’. Further studies may address if the ABA pathway is attenuated in bicolor cultivars.
Therapeutic Effects of Plant Extracts of Anoectochilus roxburghii on Side Effects of Chemotherapy in BALB/c Breast Cancer Mice
Authors: Cheng Chi-Feng , Lu Chen-Wen , Wu Wen-Jhen , Su Li-Yu , Nguyen Thi Kim Ngan , Shen Szu-Chuan , Lien Chia-Ying , Chuang Wu-Chang , Lee Ming-Chung , Wu Chung-Hsin
Published: June 2023

Breast cancer is the most common cancer in women, and chemotherapy is an effective treatment. However, chemotherapy often causes adverse side effects such as cardiotoxicity, myelosuppression, immunodeficiency, and osteoporosis. Our study focused on the alleviating effects of Anoectochilus roxburghii extracts (AREs) on the adverse side effects of chemotherapy in mice with breast cancer. We individually evaluated the antioxidant capacity and cytotoxicity of the AREs using DPPH and MTT assays. We also examined the effects of the AREs on intracellular F-actin, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) of 4T1 cancer cells before and after doxorubicin (DOX) treatment. Our results showed that ARE treatment enhanced the effects of DOX chemotherapy by promoting cell morphology damage, oxidative stress, and ROS generation, as well as by reducing MMP in the 4T1 breast cancer cells. By using BALB/c mice with breast cancer with DOX treatment, our results showed that the DOX treatment reduced body weight, blood pressure, and heart rate and induced myelosuppression, immunodeficiency, cardiotoxicity, and osteoporosis. After oral ARE treatment of BALB/c mice with breast cancer, the chemotherapeutic effects of DOX were enhanced, and the adverse side effects of DOX chemotherapy were alleviated. Based on the above results, we suggest that AREs can be used as an adjuvant reliever to DOX chemotherapy in BALB/c mice with breast cancer.
Dittrichia viscosa Selection Strategy Based on Stress Produces Stable Clonal Lines for Phytoremediation Applications
Authors: Anglana Chiara , Capaci Piergiorgio , Barozzi Fabrizio , Migoni Danilo , Rojas Makarena , Stigliano Egidio , Fanizzi Francesco Paolo , Di Sansebastiano Gian , Papadia Paride
Published: June 2023

Dittrichia viscosa uptake and translocation of the metalloid As is not fully understood and some data are contradictory, but its adaptability to this pollutant is known and is dependent on its genetic variability. D. viscosa is not a hyperaccumulator plant, but it can grow in high-drought conditions while still producing large biomass, even tolerating significant concentrations of As3+ and As5+. In spite of these remarkable characteristics, adaptive modification of performances is not predictable in wild populations. In previous work, we established experimental clonal populations to perform a functional study on the aquaporin NIP1.1. Here, we propose a strategy to select a clonal population of D. viscosa with a defined phenotype related to As tolerance and to reduced NIP1.1 expression levels for phytoremediation applications. From the previous work, we selected four independent clones, two of them belonging to the weak population (W8 and W9) and the other two belonging to the strong population (S1 and S3). The weak and strong populations differ for a different expression ratio root/shoot of DvNip1;1 that brings a different tolerance to As presence. The stress response of the populations, revealed by the CAT enzymatic test, was statistically correlated to the clones, but not to As uptake. Performance of the selected plants on a second unrelated metallic pollutant, Cd, was evaluated, showing that Cd uptake is also independent from the tolerant phenotype. In vitro culture methods using solid media and temporary immersion bioreactors were compared to propose an optimized combined protocol. The procedure yielded propagation of genetically stable tolerant clonal lines with good uptake of As and Cd. The plants, mass-produced with the developed in vitro protocol, were able to maintain their acquired abilities and are potentially able be later applied in phytoremediation or contaminated areas’ re-naturalization.
In Vitro Propagation and Genetic Uniformity Assessment of Manglietiastrum sinicum: A Critically Endangered Magnoliaceae Species
Authors: Luo Yiyang , Zheng Keyuan , Liu Xiaodi , Tao Jialu , Sun Xugao , Deng Yanwen , Deng Xiaomei
Published: June 2023

Manglietiastrum sinicum Y.W. Law is a critically endangered species with great ornamental and commercial value, which urgently requires protection. We tested different combinations of basal media and plant growth regulators to determine (i) the optimal conditions for bud induction and proliferation of explants and (ii) optimal rooting conditions. RAPD- and ISSR-PCR were used to assess the genetic fidelity of regenerated plantlets. Murashige and Skoog medium (MS) supplemented with 0.5 mg/L 6-benzyladenine (BA) and 0.05 mg/L indole-3-butyric acid (IBA) is the optimal medium for bud induction (100% induction). MSM medium (a special basal medium for M. sinicum) was more suitable for the efficient proliferation and rooting of M. sinicum. Maximum bud proliferation rate (446.20%) was obtained on MSM, with 0.4 mg/L BA, 0.5 mg/L kinetin, and 0.06 mg/L IBA, while maximum root induction rate (88.89%) was obtained on MSM supplemented with 0.4 mg/L 1-naphthylacetic acid and 1.0 mg/L IBA with a 7-day initial darkness treatment. The rooted plantlets were transferred to a substrate containing peat soil, perlite, coconut chaff, and bark (volume ratio 2:1:1:1), with a resulting survival rate of 92.2%. RAPD and ISSR markers confirmed the genetic uniformity and stability of regenerated plants.
Ecological Stoichiometry and Stock Distribution of C, N, and P in Three Forest Types in a Karst Region of China
Authors: Wang Wancai , Peng Yuanying , Chen Yazhen , Lei Shilong , Wang Xiaojun , Farooq Taimoor Hassan , Liang Xiaocui , Zhang Chao , Yan Wende , Chen Xiaoyong
Published: June 2023

Ecological stoichiometry plays important roles in understanding the nutrient constraints on tree growth and development, as well in maintaining ecosystem services in forests, yet the characteristics of carbon:nitrogen:phosphorous (C:N:P) stoichiometry in forests under karst environment have not been sufficiently evaluated. In this study, concentration, distribution, stocks of Nitrogen (N) and Phosphorous (P), and ecological stoichiometry were studied in three common forest types: Masson pine natural forests (MPNF), Masson pine plantation forests (MPPF), and Slash pine plantation forests (SPPF) in a karst region of southwestern China. Results showed that N concentrations were higher in overstory than in understory and litter in the studied forests. However, P concentration was relatively low in overstory component of the forested ecosystems. Meanwhile, the N and P concentrations were higher in SPPF in the stem and litter, while these contents were higher in MPPF and MPNP in the overstory and understory. The N and P stocks ranged from 5.7–6.2 t ha−1, and 0.5–0.6 t ha−1 in the examined forests. The ecological stoichiometry of C:N:P in the three forest types was similar in litter (46–49:2:1), and relatively steady in soil (250–320:13–16:1) and tree leaf (100–200:14–20:1). Soil P status was the primary limiting factor in affecting tree growth in MPPF and SPPF (N:P ratio > 16), while both N and P conditions were the main restrictive factors in MPNP (N:P ratio = 15) in the study area. Our study provides scientific references and useful datasets of C:N:P stoichiometry for sustainable management of forest ecosystems in karst regions.
Population Genetics, Genetic Structure, and Inbreeding of Commiphora gileadensis (L.) C. Chr Inferred from SSR Markers in Some Mountainous Sites of Makkah Province
Authors: Mansour Hassan , Alamer Khalid H. , Al-Hasawi Zaki M.
Published: June 2023

Commiphora gileadensis (L.) C. Chr is a perennial plant existing mainly in the southern and western mountains of the Arabian Peninsula. In the Makkah province, the remaining populations are threatened by many factors such as overcutting, overgrazing, and urban developments. These dangers are expected to be aggravated by the progression of aridification factors arising from climate change. To overcome the decline in remaining populations of this valuable species, a timely evaluation of the population’s genetic variables and genetic structure is vital for the conservation of existing C. gileadensis populations. In this study, we used 61 SSR primers to achieve this objective. Only 50 loci showed polymorphisms, which led to further analysis of the population genetics for 600 genotypes that were collected from 50 populations of C. gileadensis found in 10 different sites in the Makkah region: Gebel Al Muliesaa, Wadi Albathna, Wadi Houra, Wadi Albaidaa, Wadi Elebiedia, Gebel Kniethl, Wadi Sayaa, Wadi Elbarasa, Wadi Alfawara, and Wadi Alkharar. The results showed an obvious decrease in genetic diversity variables in all studied populations. The range of PPL was between 8 and 40; additionally, the low HT value of 0.804 and the high value of inbreeding, Fis = 0.238, reflected a severe lack of heterozygotes. High levels of FST and GST and low gene flow indicate considerable segregation among the C. gileadensis populations, which creates a barrier to gene migration. Our data suggest the need for conservation planning for C. gileadensis in order to avoid the species’ forthcoming extinction. Efforts should be largely oriented around managing water consumption, prohibiting overcutting and overgrazing, and establishing appropriate seed banks.
Identification and Expression of the CorA/MRS2/ALR Type Magnesium Transporters in Tomato
Authors: Liu Wen , Khan Shahbaz , Tong Mengying , Hu Haiyan , Yin Liyan , Huang Jiaquan
Published: June 2023

Magnesium (Mg2+) is the most abundant divalent ion in plants, participating in numerous metabolic processes in growth and development. CorA/MRS2/ALR type Mg2+ transporters are essential for maintaining Mg2+ homeostasis in plants. However, the candidate protein and its potential functions in the tomato plant have not been fully understood. In this study, we identified seven MGT genes (SlMRS2) in tomato based on sequence similarity, domain analysis, conserved motif identification, and structure prediction. Two SlMRS2 genes were analyzed in the bacterial strain MM281, and a functional complementary assay demonstrated their high-affinity transport of Mg2+. Quantitative real-time PCR analysis revealed that the expressions of these Mg2+ transporters were down-regulated in leaves under Mg2+ limitation, with a greater impact on lower and middle leaves compared to young leaves. Conversely, under Mg2+ toxicity, several genes were up-regulated in leaves with a circadian rhythm. Our findings indicate that members of the SlMRS2 family function as Mg2+ transporters and lay the groundwork for further analysis of their distinct functions in tomato.
On the Possible Trade-Off between Shoot and Root Biomass in Wheat
Authors: Bektas Harun , Hohn Christopher E. , Lukaszewski Adam J. , Waines John Giles
Published: June 2023

Numerous studies have shown that under a limited water supply, a larger root biomass is associated with an increased above-ground biomass. Root biomass, while genetically controlled, is also greatly affected by the environment with varying plasticity levels. In this context, understanding the relationship between the biomass of shoots and roots appears prudent. In this study, we analyze this relationship in a large dataset collected from multiple experiments conducted up to different growth stages in bread wheat (Triticum aestivum L.) and its wild relatives. Four bread wheat mapping populations as well as wild and domesticated members of the Triticeae tribe were evaluated for the root and shoot biomass allocation patterns. In the analyzed dataset the root and shoot biomasses were directly related to each other, and to the heading date, and the correlation values increased in proportion to the length of an experiment. On average, 84.1% of the observed variation was explained by a positive correlation between shoot and root biomass. Scatter plots generated from 6353 data points from numerous experiments with different wheats suggest that at some point, further increases in root biomass negatively impact the shoot biomass. Based on these results, a preliminary study with different water availability scenarios and growth conditions was designed with two cultivars, Pavon 76 and Yecora Rojo. The duration of drought and water level significantly affected the root/shoot biomass allocation patterns. However, the responses of the two cultivars were quite different, suggesting that the point of diminishing returns in increasing root biomass may be different for different wheats, reinforcing the need to breed wheats for specific environmental challenges.
Synergistic Effects of Rhizobacteria and Salicylic Acid on Maize Salt-Stress Tolerance
Authors: Ali Qasim , Ahmad Maqshoof , Kamran Muhammad , Ashraf Sana , Shabaan Muhammad , Babar Babar Hussain , Zulfiqar Usman , Haider Fasih Ullah , Ali M. Ajmal , Elshikh Mohamed S
Published: June 2023

Maize (Zea mays L.) is a salt-sensitive plant that experiences stunted growth and development during early seedling stages under salt stress. Salicylic acid (SA) is a major growth hormone that has been observed to induce resistance in plants against different abiotic stresses. Furthermore, plant growth-promoting rhizobacteria (PGPR) have shown considerable potential in conferring salinity tolerance to crops via facilitating growth promotion, yield improvement, and regulation of various physiological processes. In this regard, combined application of PGPR and SA can have wide applicability in supporting plant growth under salt stress. We investigated the impact of salinity on the growth and yield attributes of maize and explored the combined role of PGPR and SA in mitigating the effect of salt stress. Three different levels of salinity were developed (original, 4 and 8 dS m−1) in pots using NaCl. Maize seeds were inoculated with salt-tolerant Pseudomonas aeruginosa strain, whereas foliar application of SA was given at the three-leaf stage. We observed that salinity stress adversely affected maize growth, yield, and physiological attributes compared to the control. However, both individual and combined applications of PGPR and SA alleviated the negative effects of salinity and improved all the measured plant attributes. The response of PGPR + SA was significant in enhancing the shoot and root dry weights (41 and 56%), relative water contents (32%), chlorophyll a and b contents (25 and 27%), and grain yield (41%) of maize under higher salinity level (i.e., 8 dS m−1) as compared to untreated unstressed control. Moreover, significant alterations in ascorbate peroxidase (53%), catalase (47%), superoxide dismutase (21%), MDA contents (40%), Na+ (25%), and K+ (30%) concentration of leaves were pragmatic under combined application of PGPR and SA. We concluded that integration of PGPR and SA can efficiently induce salinity tolerance and improve plant growth under stressed conditions.