bluuebunny/crossref_metadata_2025 huggingface dataset:
Moderate-to-Severe Malnutrition Identified by the Controlling Nutritional Status (CONUT) Score Is Significantly Associated with Treatment Failure of Periprosthetic Joint Infection
Authors: Li Zhuo , Maimaiti Zulipikaer , Li Zhi-Yuan , Fu Jun , Hao Li-Bo , Xu Chi , Chen Ji-Ying
Published: October 2022

The prevalence and role of malnutrition in periprosthetic joint infection (PJI) remain unclear. This study aimed to use measurable nutritional screening tools to assess the prevalence of malnutrition in PJI patients during two-stage exchange arthroplasty and to explore the association between malnutrition and treatment failure. Our study retrospectively included 183 PJI cases who underwent 1st stage exchange arthroplasty and had available nutritional parameters, of which 167 proceeded with 2nd stage reimplantation. The recently proposed Musculoskeletal Infection Society (MSIS) Outcome Reporting Tool was used to determine clinical outcomes. The Controlling Nutritional Status (CONUT), Nutritional Risk Index (NRI), and Naples Prognostic Score (NPS) were used to identify malnutrition at 1st and 2nd stage exchange, respectively. Multivariate logistic regression analyses were performed to determine the association between malnutrition and treatment failure. Restricted cubic spline models were further used to explore the dose–response association. Additionally, risk factors for moderate-to-severe malnutrition were evaluated. Malnourished patients identified by CONUT, NPS, and NRI accounted for 48.1% (88/183), 98.9% (181/183), and 55.7% (102/183) of patients at 1st stage, and 9.0% (15/167), 41.9% (70/167), and 43.1% (72/167) at 2nd stage, indicating a significant improvement in nutritional status. We found that poorer nutritional status was a predictor of treatment failure, with CONUT performing best as a predictive tool. Moderate-to-severe malnutrition at 1st stage identified by CONUT was significantly related to treatment failure directly caused by PJI (odds ratio [OR] = 5.86), while the OR was raised to 12.15 at 2nd stage (OR = 12.15). The linear dose–response associations between them were also confirmed (P for nonlinearity at both 1st and 2nd stage > 0.05). As for total treatment failure, moderate-to-severe malnutrition as determined by CONUT was associated with a 1.96-fold and 8.99-fold elevated risk at the 1st and 2nd stages, respectively. Age ≥ 68 years (OR = 5.35) and an increased number of previous surgeries (OR = 2.04) may be risk factors for moderate-to-severe malnutrition. Overall, the prevalence of malnutrition in PJI patients is very high. Given the strong association between moderate-to-severe malnutrition identified by CONUT and PJI treatment failure, COUNT could be a promising tool to evaluate the nutritional status of PJI patients to optimize treatment outcomes.
Is the Use of Artificial Sweeteners Beneficial for Patients with Diabetes Mellitus? The Advantages and Disadvantages of Artificial Sweeteners
Authors: Iizuka Katsumi
Published: October 2022

Artificial sweeteners have been developed as substitutes for sugar. Sucralose, acesulfame K (ACE K), aspartame, and saccharin are artificial sweeteners. Previously, artificial sweeteners were thought to be effective in treating obesity and diabetes. Human meta-analyses have reported that artificial sweeteners have no effect on body weight or glycemic control. However, recent studies have shown that artificial sweeteners affect glucose absorption in the intestinal tract as well as insulin and incretin secretion in humans and animals. Moreover, artificial sweeteners alter the composition of the microbiota and worsen the glycemic control owing to changes in the gut microbiota. The early intake of ACE K was also shown to suppress the taste response to sugar. Furthermore, a large cohort study showed that high artificial sweetener intake was associated with all-cause mortality, cardiovascular risk, coronary artery disease risk, cerebrovascular risk, and cancer risk. The role of artificial sweeteners in the treatment of diabetes and obesity should be reconsidered, and the replacement of sugar with artificial sweeteners in patients will require the long-term tracking of not only intake but also changes in blood glucose and weight as well as future guidance based on gut bacteria data. To utilize the beneficial properties of artificial sweeteners in treatment, further studies are needed.
Dissecting Supplement and Nutrients Intake of Adults with and without COVID-19 History through the Lens of Health Belief Model
Authors: Mahmudiono Trias , Yuniar Cindra Tri , Dewi Risti Kurnia , Rachmah Qonita , Atmaka Dominikus Raditya , Zebadia Eurika , Sahila Nur , Wijanarko Mutiara Arsya Vidianinggar , Haliman Chika Dewi , Tang Shirley Gee Hoon
Published: October 2022

Over the past two years, the world has faced the pandemic, COVID-19, and various changes. Several regulations and recommendations from the Ministry of Health of Indonesia have contributed to behavioral changes among Indonesian residents, especially in food consumption patterns. The change in food consumption patterns can be a positive change that formed due to the COVID-19 pandemic. This study aimed to examine whether the application of a Health Belief Model (HBM)-based nutrition education programme can be effectively used in changing the beliefs of adults with or without a COVID-19 history in supplement and nutrient intake. This study was a cross-sectional study involving 140 adults. This study placed 70 adults with/without a COVID-19 history into the intervention group. The intervention group participated in a nutrition education programme. The respondents were asked to fill out the questionnaire. The data were analyzed by independent and paired t-tests and Chi-square test. The result of this study showed no association between perceived susceptibility, severity, benefit, barrier, and self-efficacy, of nutrient and supplement intake with the history of COVID-19 among the respondents. However, most of the respondents in this study were low in their scores of perceivedness. Thus, it is still important for the government to increase nutrient and supplement intake education, especially in young adults aged below 25 years old.
Testosterone Deficiency and Nutritional Parameters as Predictors of All-Cause Mortality among Male Dialysis Patients
Authors: Leśniak Ksymena , Rymarz Aleksandra , Sobol Maria , Dymus Jolanta , Woźniak-Kosek Agnieszka , Niemczyk Stanisław
Published: October 2022

Background: Chronic kidney disease (CKD) is associated with an accelerated risk of cardiovascular mortality. Hormonal and metabolic disorders in CKD may constitute novel risk factors. Our objective was to characterize and evaluate prognostic implications of circulating sex steroids and selected nutritional parameters in patients at different stages of CKD. Methods: Studied groups were composed of 78 men: 31 on hemodialysis (HD), 17 on peritoneal dialysis (PD), 30 with CKD stage G3-G4. Total testosterone (TT), dehydroepiandrosterone sulphate (DHEA-S), androstenedione, luteinizing hormone (LH), prolactin (PRL), and biochemical parameters were measured; Free testosterone (FT) was calculated. Results: The lowest TT and FT were observed in HD, the highest- in CKD (p = 0.006 for TT, p = 0.005 for FT). TT positively correlated with total cholesterol in HD (p = 0.012), FT negatively correlated with BMI in CKD (p = 0.023). During the 12 months, 9 patients died (5 in the HD, 4 in the PD group). The deceased group had significantly lower concentrations of albumin (p = 0.006) and prealbumin (p = 0.001), and a significantly higher concentration of androstenedione (p = 0.019) than the surviving group. In the group of men on dialysis, a serum TT concentration <2.55 ng/mL (Q1-first quartile) was associated with a 3.7-fold higher risk of death, although statistical significance was not achieved (p = 0.198). After analysis of the ROC curves, the FT level was the best prognostic marker in HD (AUC = 0.788; 95% CI: 0.581–0.996; p = 0.006) Conclusions: Total and free testosterone levels were lower in the HD group than in the CKD group. The nutritional status undoubtedly affects the survival of dialysis patients but also the concentrations of testosterone significantly contributes to further worsening the prognosis.
Lactic Acid Bacteria: A Promising Tool for Menopausal Health Management in Women
Authors: Chen Qian , Wang Haojue , Wang Gang , Zhao Jianxin , Chen Haiqin , Lu Xianyi , Chen Wei
Published: October 2022

Menopause is a period during which women undergo dramatic hormonal changes. These changes lead to physical and mental discomfort, are greatly afflictive, and critically affect women’s lives. However, the current safe and effective management measures for women undergoing menopause are insufficient. Several probiotic functions of lactic acid bacteria (LAB) have been recognized, including alleviation of lactose intolerance, protection of digestive tract health, activation of the immune system, protection against infections, improvement of nutrient uptake, and improvement of the microbiota. In this review, we highlight the currently available knowledge of the potential protective effects of LAB on preventing or mitigating menopausal symptoms, particularly in terms of maintaining balance in the vaginal microbiota, reducing bone loss, and regulating the nervous system and lipid metabolism. Given the increasing number of women entering menopause and the emphasis on the management of menopausal symptoms, LAB are likely to soon become an indispensable part of clinical/daily care for menopausal women. Herein, we do not intend to provide a comprehensive analysis of each menopausal disorder or to specifically judge the reliability and safety of complementary therapies; rather, we aim to highlight the potential roles of LAB in individualized treatment strategies for the clinical management of menopause.
Preventive Mechanism of Lycopene on Intestinal Toxicity Caused by Cyclophosphamide Chemotherapy in Mice by Regulating TLR4-MyD88/TRIF-TRAF6 Signaling Pathway and Gut-Liver Axis
Authors: Pan Xiao , Niu Xiaoyan , Li Yaping , Yao Yupei , Han Lirong
Published: October 2022

Cyclophosphamide (CYC) is the first-line chemotherapy drug for cancer in clinical practice, and its intestinal toxicity seriously affects the treatment effect and prognosis of patients. Lycopene (LP) is the main pigment of ripe tomatoes and has strong antioxidant activity. However, the mechanism by which LP prevents CYC-induced intestinal injury remains unclear. The aim of this study was to investigate the mechanism of LP in preventing intestinal toxicity caused by CYC chemotherapy in mice. The results showed that LP significantly prevented spleen and thymus atrophy induced by CYC. In terms of intestinal injury, LP significantly increased the levels of superoxide dismutase (SOD), secretory immunoglobulin A (sIgA), interleukin (IL)-4, IL-12, and interferon (IFN)-γ, decreased the content of lipid oxidation (MDA), upregulated the protein expressions of toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), toll/IL-1receptor domain containing adaptor protein inducing IFN-β (TRIF), p-P38 MAPK (P38), and p-nuclear factor kappa-B (NF-κB) p65, and improved the small intestine tissue injury induced by CYC. In terms of liver injury, LP significantly increased the content of glutathione (GSH), decreased the contents of MDA, nitric oxide (NO), IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and repaired the liver tissue injury induced by CYC. Importantly, 10 mg/kg LP significantly prevented intestinal microbiota dysregulation in CYC mice. These results suggested that LP significantly prevented intestinal injury induced by CYC in mice by regulating the TLR4-MyD88/TRIF-TRAF6 signaling pathway and gut-liver axis.
Urinary Potential Renal Acid Load (uPRAL) among Vegans Versus Omnivores and Its Association with Bone Health in the Cross-Sectional Risks and Benefits of a Vegan Diet Study
Authors: Penczynski Katharina J. , Remer Thomas , Menzel Juliane , Abraham Klaus , Weikert Cornelia
Published: October 2022

Both veganism and high dietary acid load are linked to unfavorable bone health. However, the specific role of dietary alkali or acid load for the bone health of vegans is so far unknown. Thus, the renal biomarker for dietary acid or alkali load, i.e., urinary potential renal acid load (uPRAL), was measured in 24 h urine samples of 34 vegans and 35 omnivores (50.7% males). Bone health was assessed via calcaneal quantitative ultrasound. Associations between uPRAL and bone health indices were examined using multivariable general linear models. Compared to omnivores, vegans had a significantly lower uPRAL (mean difference = −34.5 mEq/24 h, p < 0.0001), a lower 24 h urinary phosphate excretion (p = 0.0004), a lower 24 h urinary sulfate excretion (p = 0.01), and a higher urine pH value (p < 0.0001). Broadband ultrasound attenuation (BUA) was lower among vegans versus omnivores (p = 0.037), yet it was not associated with uPRAL irrespective of adjustments. This study confirms different acid-base profiles of vegans and omnivores, with a pronounced alkaline excess among vegans and a rather low acid load among a group of omnivores with moderate protein intake. Within this spectrum of alkaline to low acid load, no association with bone health was found.
Humidity and Light Modulate Oxygen-Induced Viability Loss in Dehydrated Haematococcus lacustris Cells
Authors: Roach Thomas , Fambri Alessandro , Ballesteros Daniel
Published: October 2022

Haematoccocus lacustris (previously H. pluvialis) is a desiccation-tolerant unicellular freshwater green alga. During acclimation to desiccation, astaxanthin-rich lipid bodies and low-molecular-weight antioxidants (α-tocopherol, glutathione) accumulate, while the chloroplast area and chlorophyll contents decrease, which may facilitate desiccation tolerance by preventing damage mediated by reactive oxygen species (ROS). Here, we investigated the influence of moisture, light, oxygen, and temperature on redox homeostasis and cell longevity. Respiration and unbound freezable water were detectable in cells equilibrated to ≥90% relative humidity (RH), a threshold above which viability considerably shortened. At 92.5% RH and 21 °C, antioxidants depleted over days as cells lost viability, especially in an oxygen-rich atmosphere, supporting the role of ROS production in uncoupled respiration in viability loss. At 80% RH and 21 °C, redox homeostasis was maintained over weeks, and longevity was less influenced by oxygen. Light and oxygen was a lethal combination at 92.5% RH, under which pigments bleached, while in the dark only astaxanthin bleached. Viability positively correlated with glutathione concentrations across all treatments, while correlation with α-tocopherol was weaker, indicating limited viability loss from lipid peroxidation at 80% RH. In cells equilibrated to 50% RH, longevity and redox homeostasis showed strong temperature dependency, and viability was maintained at sub-zero temperatures for up to three years, revealing cryogenic storage to be an optimal strategy to store H. lacustris germplasm.
Blastocystis sp. Infection: Prevalence and Clinical Aspects among Patients Attending to the Laboratory of Parasitology–Mycology of Fann University Hospital, Dakar, Senegal
Authors: Sylla Khadime , Sow Doudou , Lelo Souleye , Dieng Thérèse , Tine Roger Clément , Faye Babacar
Published: October 2022

Introduction: Blastocystis sp. is a unicellular obligate anaerobic protozoa found in the human intestinal tract. Its role in human health is widely discussed because of the high proportion of asymptomatic carriers. In sub-Saharan Africa, the prevalence of the disease is underestimated. This study was performed to describe the epidemiological, clinical, and parasitological aspects of Blastocystis sp. infection in patients attending to Fann University Hospital. Material and Methods: We carried out a retrospective and descriptive study among patients attending to the laboratory of Parasitology and Mycology of Fann University Hospital from January 2016 to December 2020. All stool samples collected were examined using direct examination, a formal ether concentration method, and a modified Zeilh–Nielsen staining method. A descriptive analysis was performed with Stata MP 16 software. The significance level was set at 5%. Results: Overall, 447 cases of Blastocystis sp. were reported in our study, representing a prevalence rate of 13.7% ((447/3264) (95% CI: 12.5–15.5)). The mean age of the patients was 26 ± 20.7 years. Subjects over 45 years of age were more affected, with a frequency of 14.7%. Blastocystis sp. carriage was more common in males, at 14.6%. The symptomatology was mainly represented by diarrhea, abdominal pain, and dyspeptic disorders. In asymptomatic patients, the frequency of Blastocystis sp. was 33.3%. Mono-infection was found in 78.6% of cases. In total, 96 patients were carriers of at least two parasites (21.5%). Blastocystis sp. was most associated with Entamoeba coli (8.1%) and Endolimax nanus (4.03%). The association with helminths was noted in 5 patients (3 Ascaris lumbricoides, Trichuris trichiura, and Taenia). Conclusion: These results show the frequency of Blastocystis sp. infection with a large proportion of asymptomatic carriers. The presence of the parasite in the stool, associated with digestive disorders or with the association of other intestinal parasites, could justify the initiation of an anti-parasitic treatment.
Antimicrobial Resistance and Virulence Factors of Proteus mirabilis Isolated from Dog with Chronic Otitis Externa
Authors: Kwon Jun , Yang Myoung-Hwan , Ko Hyoung-Joon , Kim Sang-Guen , Park Chul , Park Se-Chang
Published: October 2022

Otitis externa is among the most prevalent diseases in dogs. If the underlying cause is not addressed, bacterial reinfection becomes frequent, necessitating antibiotic administration for an extended period of time. Prolonged treatment promotes the emergence of antibiotic-resistant bacteria and increases the risk of their transmission from animals to humans. This study aimed to analyze the antibiotic resistance pattern of the emerging pathogen Proteus mirabilis to identify bacterial virulence and antibiotic selection. Samples were collected from randomly encountered dogs with chronic otitis externa. Thirty-two strains of P. mirabilis were isolated and identified, using MALDI-TOF. The Kirby-Bauer disk diffusion method was used to assess the antibiotic susceptibility of P. mirabilis to 11 antibiotics. The isolates (n = 32) were most resistant to cefazolin (75%), trimethoprim–sulfamethoxazole (72%), chloramphenicol (72%), amoxicillin–clavulanate (63%), ampicillin (59%), cefepime (56%), ciprofloxacin (53%), aztreonam (50%), ceftazidime avibactam (50%), gentamicin (22%), and amikacin (16%). Moreover, 75% of isolates were found to be multidrug-resistant bacteria. P. mirabilis was found to have a high resistance-pattern ratio. Although the exact cause is unknown, continuous antibiotic use is thought to be a major factor. We concluded that antibiotic use must be prudent and selective to prevent antibiotic resistance.
Targeting NMDA Receptor Complex in Management of Epilepsy
Authors: Sivakumar Shravan , Ghasemi Mehdi , Schachter Steven C.
Published: October 2022

N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy. In this review, we provide an update on the pathologic role of NMDARs in epilepsy and an overview of the NMDAR antagonists that have been evaluated as anticonvulsive agents in clinical studies, as well as in preclinical seizure models.
Repurposing Lenvatinib as A Potential Therapeutic Agent against Thyroid Eye Disease by Suppressing Adipogenesis in Orbital Adipose Tissues
Authors: Cheng Lu , Hu Jing , Zhang Ling , Shen Ning , Chen Hui , Zhang Fang
Published: October 2022

Thyroid eye disease (TED) is the most common orbital disease in adults. Targeting expanded orbital adipose tissue (OAT) removed by surgery has therapeutic potential. However, drugs targeting OAT are unavailable because of the lack of deciphering features of OAT. Here, we aimed to investigate the mechanism underlying OAT expansion and identify a drug targeting OAT in TED. We found an increasing number of adipocytes with smaller size in TED-derived OATs as compared with controls, indicating that hyperplasia rather than hypertrophy contributed to OAT enlargement in TED. Typically smaller-sized adipocytes in TED patient-derived OATs were noted to localize surrounding vessels. RNA sequencing revealed enriched vascular endothelial growth factor receptor (VEGFR) genes in adipocytes differentiated from preadipocytes of TED-derived stromal vascular fraction (SVF). Similarly, OATs in patients with TED also expressed a higher level of VEGFR-1 and -2. We induced adipogenesis in TED-derived SVF with or without Lenvatinib, an FDA-approved small-molecule VEGFR inhibitor. Lenvatinib significantly suppressed lipid accumulation in a dose-dependent manner. In conclusion, our study revealed the potential anti-adipogenic effect of Lenvatinib on the OAT of TED-affected patients. In addition to proposing a drug for TED treatment, this study shows the therapeutic potential of anti-adipogenesis drugs targeting the VEGF pathway.
The N-Substituted-4-Methylbenzenesulphonyl Hydrazone Inhibits Angiogenesis in Zebrafish Tg(fli1: EGFP) Model
Authors: Gawrońska-Grzywacz Monika , Piątkowska-Chmiel Iwona , Popiołek Łukasz , Herbet Mariola , Dudka Jarosław
Published: October 2022

One of the most important therapies of malignant neoplasms, which are the second cause of death worldwide, is focused on the inhibition of pathological angiogenesis within the tumor. Therefore, the searching for the efficacious and relatively inexpensive small-molecule inhibitors of this process is essential. In this research, the anti-angiogenic potential of N-substituted-4-methylbenzenesulphonyl hydrazone, possessing antiproliferative activity against cancer cells, was tested. For this purpose, an intersegmental vessel (ISV) angiogenesis assay was performed using 6 hpf (hours post fertilization), 12 hpf and 24 hpf embryos of zebrafish transgenic strain, Tg(fli1: EGFP). They were incubated with different concentrations of tested molecule and after 24 h the development of intersegmental vessels of the trunk was analysed. In turn, the acute toxicity study in the zebrafish model was mainly conducted on strain AB, using the OECD-approved and recommended fish embryo acute toxicity test (FET) procedure. The results showed the moderate toxicity of N-[(3-chloro-4-methoxyphenyl)methylidene]-4-methylbenzenesulphonohydrazide in above-mentioned model with the LC50 value calculated at 23.04 mg/L. Moreover, newly synthesized molecule demonstrated the anti-angiogenic potential proved in Tg(fli1: EGFP) zebrafish model, which may be promising for the therapy of neoplastic tumors as well as other diseases related to pathological angiogenesis, such as age-related macular degeneration and diabetic retinopathy.
Neuroprotective Effect of Red Sea Marine Sponge Xestospongia testudinaria Extract Using In Vitro and In Vivo Diabetic Peripheral Neuropathy Models
Authors: Magadmi Rania , Borouk Kariman , Youssef Diaa T. A. , Shaala Lamiaa A. , Alrafiah Aziza R. , Shaik Rasheed A. , Alharthi Sameer E.
Published: October 2022

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Oxidative stress plays an important role in the pathophysiology of DPN. Red Sea marine sponge Xestospongia testudinaria extract has a promising neuroprotective effect, presumably owing to its antioxidant and anti-inflammatory properties. Thus, this study aimed to investigate the neuroprotective effect of the sponge X. testudinaria extract on in vitro and in vivo models of DPN. Mice dorsal root ganglia (DRG) were cultured with high glucose (HG) media and used as an in vitro model of DPN. Some of the DRGs were pre-treated with 2 mg/mL of X. testudinaria. The X. testudinaria extract significantly improved the HG-induced decreased neuronal viability and the neurite length. It improved the oxidative stress biomarkers in DRG cultures. The DPN model was induced in vivo by an injection of streptozotocin at a dose of 150 mg/kg in mice. After 35 days, 0.75 mg/kg of the X. testudinaria extract improved the hot hyperalgesia and the DRG histology. Although the sponge extract did not reduce hyperglycemia, it ameliorated the oxidative stress markers and pro-inflammatory markers in the DRG. In conclusion, the current study demonstrates the neuroprotective effect of Red Sea sponge X. testudinaria extract against experimentally induced DPN through its antioxidant and anti-inflammatory mechanisms.
Exosomes as CNS Drug Delivery Tools and Their Applications
Authors: Sun Ke , Zheng Xue , Jin Hongzhen , Yu Fan , Zhao Wei
Published: October 2022

Central nervous system (CNS) diseases threaten the health of people all over the world. However, due to the structural and functional particularities of the brain and spinal cord, CNS-targeted drug development is rather challenging. Exosomes are small cellular vesicles with lipid bilayers that can be secreted by almost all cells and play important roles in intercellular communication. The advantages of low immunogenicity, the ability to cross the blood-brain barrier, and the flexibility of drug encapsulation make them stand out among CNS drug delivery tools. Herein, we reviewed the research on exosomes in CNS drug delivery over the past decade and outlined the impact of the drug loading mode, administration route, and engineered modification on CNS targeting. Finally, we highlighted the problems and prospects of exosomes as CNS drug delivery tools.
Antioxidant, Antimicrobial, and Kinetic Studies of Β-Cyclodextrin Crosslinked with Lignin for Drug Delivery
Authors: Anghel Narcis , Melinte Violeta , Spiridon Iuliana , Pertea Mihaela
Published: October 2022

β-Cyclodextrin was attached to lignin/lignin crosslinked by epichlorohydrin and served as a drug delivery matrix. Ketoconazole and piroxicam were added into the polymeric matrix as antifungal and anti-inflammatory agents, respectively. The percentage of drug retained ranged from 48.4% to 58.4% for ketoconazole and piroxicam, respectively. It was found that their tensile strengths increased with decreasing particle size, ranging between 59% and 71% for lignin crosslinked with β-cyclodextrin base matrix (LCD). Depending on the polymeric matrix, the drug release kinetics fit well in the Korsmeyer–Peppas model, with or without Fickian diffusion. From the materials based on the mixture of epoxidized lignin and β-cyclodextrin, the medicines were released more slowly (the release rate constant presents lower values ranging between 1.117 and 1.783), as compared with those comprising LCD (2.210–4.824). The materials were also demonstrated to have antimicrobial activity. The antioxidant activity of LCD loaded with piroxicam was found to be 23.9% greater than that of the base matrix (LCD). These findings could be useful towards β-cyclodextrin attached to lignin formulation development of drug carriers with antioxidant activity.
Arginine-Modified 3D-Printed Chromatographic Supports
Authors: Valente Joana F. A. , Carreira Tiago Soares , Dias Juliana R. , Sousa Fani , Alves Nuno
Published: October 2022

The increasing progression of biopharmaceutical-based therapies highlights the demand for efficient chromatographic methods that can be used to purify the desired biomolecules (e.g., nucleic acids, enzymes, or monoclonal antibodies) which are presently under consideration in clinical trials or approved by the Food and Drug Administration. These molecules present distinct chemical and structural properties, which are critical cues for the development and production of adequate chromatographic supports. Until now, it has not been possible to fully control the characteristics of the chromatographic matrices to assure the total reproducibility of their structure and packing. Meanwhile, three-dimensional printing (3DP) is in the early stage of its use in the production of chromatographic supports as a fast, very precise, and reproducible methodology. Although 3DP can provide excellent performance properties to the chromatographic structures, it cannot, per se, lead to high-quality pharmaceutical products. However, the association of affinity ligands, such as amino acids, which is possible in 3DP, could enable the attainment of high-purity yields of the desired molecules. Beyond the amino acids most widely studied as chromatographic ligands, arginine has been successfully immobilized on different chromatographic supports (namely, agarose bead matrices, macroporous matrices, and monoliths) to achieve extra-pure gene therapy products. In this research, we studied the immobilization of arginine on 3DP chromatographic supports, evaluating the stability of the ligand/chromatographic support linkage under different chromatographic conditions to determine the robustness of these new prototypes. Moreover, we also applied plasmid DNA samples to these supports to observe the practical behaviour of the developed arginine 3DP chromatographic structures.
Design, Formulation, and Characterization of Valsartan Nanoethosomes for Improving Their Bioavailability
Authors: Nasr Ali M. , Moftah Fayrouz , Abourehab Mohammed A. S. , Gad Shadeed
Published: October 2022

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (−51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0–∞). The AUC (0–∞) with oral treatment was 7.0 ± 2.94 (μg.h/mL), but the AUC (0–∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (μg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel.
Effect of the Silica–Magnetite Nanocomposite Coating Functionalization on the Doxorubicin Sorption/Desorption
Authors: Demin Alexander M. , Vakhrushev Alexander V. , Valova Marina S. , Korolyova Marina A. , Uimin Mikhail A. , Minin Artem S. , Pozdina Varvara A. , Byzov Iliya V. , Tumashov Andrey A. , Chistyakov Konstantin A. , Levit Galina L. , Krasnov Victor P. , Charushin Valery N.
Published: October 2022

A series of new composite materials based on Fe3O4 magnetic nanoparticles coated with SiO2 (or aminated SiO2) were synthesized. It has been shown that the use of N-(phosphonomethyl)iminodiacetic acid (PMIDA) to stabilize nanoparticles before silanization ensures the increased content of a SiO2 phase in the Fe3O4@SiO2 nanocomposites (NCs) in comparison with materials obtained under similar conditions, but without PMIDA. It has been demonstrated for the first time that the presence of PMIDA on the surface of NCs increases the level of Dox loading due to specific binding, while surface modification with 3-aminopropylsilane, on the contrary, significantly reduces the sorption capacity of materials. These regularities were in accordance with the results of quantum chemical calculations. It has been shown that the energies of Dox binding to the functional groups of NCs are in good agreement with the experimental data on the Dox sorption on these NCs. The mechanisms of Dox binding to the surface of NCs were proposed: simultaneous coordination of Dox on the PMIDA molecule and silanol groups at the NC surface leads to a synergistic effect in Dox binding. The synthesized NCs exhibited pH-dependent Dox release, as well as dose-dependent cytotoxicity in in vitro experiments. The cytotoxic effects of the studied materials correspond to their calculated IC50 values. NCs with a SiO2 shell obtained using PMIDA exhibited the highest effect. At the same time, the presence of PMIDA in NCs makes it possible to increase the Dox loading, as well as to reduce its desorption rate, which may be useful in the design of drug delivery vehicles with a prolonged action. We believe that the data obtained can be further used to develop stimuli-responsive materials for targeted cancer chemotherapy.
Comparison of the Robustness of Pellet Film Coating with and without In-Process Coating Thickness Evaluation
Authors: Brezovar Teja , Svetič Sandi , Dreu Rok
Published: October 2022

The robustness of the pellet coating process with and without the use of an in-process coating thickness analyzer (PATVIS APA) was investigated. Pellets containing model drug were coated with a prolonged release film coating, using different process conditions. In the first set of experiments film coating was performed as process repetitions with unintentional variation of process parameters, and in the second set, controlled changes (inlet air humidity, gap between distribution plate and Wurster partition, starting pellet load) were made. Within the first set of experiments, the coating process endpoint was determined either via gravimetric consumption of coating dispersion or by means of in-line coating thickness monitoring. The release profiles of the pellets were analyzed and the density of coating calculated. Both methods of the process endpoint determination can be relatively robust in batch processing, if key factors influencing drug release profile are under control. PATVIS APA was shown to be a useful tool to better understand the coating process and can be helpful if coating process interruptions are encountered. Water content was shown to be the key factor influencing the drug profile, presumably by influencing the structure and thickness of the coating applied.
Mitophagy Induced by Metal Nanoparticles for Cancer Treatment
Authors: Mundekkad Deepa , Cho William C.
Published: October 2022

Research on nanoparticles, especially metal nanoparticles, in cancer therapy is gaining momentum. The versatility and biocompatibility of metal nanoparticles make them ideal for various applications in cancer therapy. They can bring about apoptotic cell death in cancer cells. In addition to apoptosis, nanoparticles mediate a special type of autophagy facilitated through mitochondria called mitophagy. Interestingly, nanoparticles with antioxidant properties are capable of inducing mitophagy by altering the levels of reactive oxygen species and by influencing signaling pathways like PINK/Parkin pathway and P13K/Akt/mTOR pathway. The current review presents various roles of metal nanoparticles in inducing mitophagy in cancer cells. We envision this review sheds some light on the blind spots in the research related to mitophagy induced by nanoparticles for cancer treatment.
Properties of Compacts from Mixtures of Calcium Fluoride Micro- and Nanopowders
Authors: Ilves Vladislav G. , Sokovnin Sergey Yu. , Zayats Sergey V. , Zuev Mikhail G.
Published: October 2022

In this work, compacts from mechanical mixtures of CaF2 micron powder (MCP) with CaF2 nanopowder (NP) additives were produced, with mass ratios of the mixture components ranging from 10:0.125 to 10:1, respectively, using magnetic pulse (MP) and static pressing (SP) methods. The effects of pressure (Pp) and pressing temperature (Tp), concentration and phase composition of the additive on the density and color of compacts were studied, taking into account the properties of the initial components of the mixtures. The evolution of pulsed cathodoluminescence (PCL) spectra and photoluminescence (PL) of compacts from pure powders and their mixtures depending on Pp, Tp and characteristics of initial CaF2 NP was also studied. A new near-infrared (NIR) band associated with fluoride vacancies was discovered with a maximum at ~765 nm in PCL spectra of compacts produced by MP at a temperature of 425 °C. A blue band at 435 nm associated with impurity oxygen vacancies in the CaF2 lattice was found in PL spectra compacts of pure NP and powder mixtures. The density of compacts of pure NP and MCP reached 89% of the theoretical density, and the density of compacts of mixtures did not exceed 78%. The defective structure and phase composition of the CaF2 NP had a decisive effect on the luminescent properties of compacts from mixtures of micro- and nanopowders.
Design of Multi-Wavelength Diffractive Lenses Focusing Radiation of Different Wavelengths to Different Points
Authors: Doskolovich Leonid L. , Skidanov Roman V. , Blank Veronika A. , Ganchevskaya Sofiya V. , Podlipnov Vladimir V. , Bykov Dmitry A. , Golovastikov Nikita V. , Bezus Evgeni A.
Published: October 2022

We propose a method for calculating the so-called multi-wavelength diffractive lenses (MWDLs) intended for separating and focusing the radiation of L given wavelengths to L given points located in a certain plane perpendicular to the optical axis. The method is based on minimizing the objective function characterizing the deviation of the complex transmission functions of the MWDL from the complex transmission functions of diffractive lenses focusing the design wavelengths to the given points. In the method, the MWDL calculation is reduced to a set of independent pointwise optimization problems, each of which describes the calculation of the MWDL microrelief at one point. The presented results of the numerical simulation of the designed MWDLs confirm high performance of the proposed method. The numerical simulation results are confirmed by the results of experimental investigations, including the fabrication of MWDLs using the direct laser writing technique and the study of the MWDL operation in an optical experiment.
A Multi-Level Approach as a Powerful Tool to Identify and Characterize Some Italian Autochthonous Common Bean (Phaseolus vulgaris L.) Landraces under a Changing Environment
Authors: Falcione Martina , Simiele Melissa , Renella Alessandra , Scippa Gabriella Stefania , Di Martino Paolo , Trupiano Dalila
Published: October 2022

A prime role in matters of agrobiodiversity is held by landraces, which serve as a repository gene pool able to meet sustainable development goals and to face the ongoing challenges of climate change. However, many landraces are currently endangered due to environmental and socio-economic changes. Thus, effective characterization activities and conservation strategies should be undertaken to prevent their genetic and cultural erosion. In the current study, the morphological, genetic, and biochemical analyses were integrated with stress response-related studies to characterize the diversity of seven Italian autochthonous common bean landraces. The results showed that the morphological descriptors and the neutral molecular markers represent powerful tools to identify and distinguish diversity among landrace populations, but they cannot correlate with the stress tolerance pattern of genetically similar populations. The study also supported the use of proline as a biochemical marker to screen the most salt-sensitive bean landraces. Thus, to fully elucidate the future dynamics of agrobiodiversity and to establish the basis for safeguarding them while promoting their utilization, a multi-level approach should always be included in any local and national program for the characterization/conservation/use of genetic resources. This study should represent the basis for further joint research that effectively contributes to set/achieve Italian priorities towards sustainability in the framework of emerging environmental, societal, and economic challenges.
Evaluation of Chemical Composition of Miscanthus × giganteus Raised in Different Climate Regions in Russia
Authors: Gismatulina Yulia A. , Budaeva Vera V. , Kortusov Aleksey N. , Kashcheyeva Ekaterina I. , Gladysheva Evgenia K. , Mironova Galina F. , Skiba Ekaterina A. , Shavyrkina Nadezhda A. , Korchagina Anna A. , Zolotukhin Vladimir N. , Sakovich Gennady V.
Published: October 2022

Lignocellulosic biomass is of great interest as an alternative energy resource because it offers a range of merits. Miscanthus × giganteus is a lignocellulosic feedstock of special interest, as it combines a high biomass productivity with a low environmental impact, including CO2 emission control. The chemical composition of lignocellulose determines the application potential for efficient industrial processing. Here, we compiled a sample collection of Miscanthus × giganteus that had been cultivated in different climate regions between 2019 and 2021. The chemical composition was quantified by the conventional wet methods. The findings were compared with each other and with the known data. Starting as soon as the first vegetation year, Miscanthus was shown to feature the following chemical composition: 43.2–55.5% cellulose content, 17.1–25.1% acid-insoluble lignin content, 17.9–22.9% pentosan content, 0.90–2.95% ash content, and 0.3–1.2% extractives. The habitat and the surrounding environment were discovered herein to affect the chemical composition of Miscanthus. The stem part of Miscanthus was found to be richer in cellulose than the leaf (48.4–54.9% vs. 47.2–48.9%, respectively), regardless of the planation age and habitat. The obtained findings broaden the investigative geography of the chemical composition of Miscanthus and corroborate the high value of Miscanthus for industrial conversion thereof into cellulosic products worldwide.
Physiological Response, Oxidative Stress Assessment and Aquaporin Genes Expression of Cherry Tomato (Solanum lycopersicum L.) Exposed to Hyper-Harmonized Fullerene Water Complex
Authors: Subotić Angelina , Jevremović Slađana , Milošević Snežana , Trifunović-Momčilov Milana , Đurić Marija , Koruga Đuro
Published: October 2022

The rapid production and numerous applications of nanomaterials warrant the necessity and importance of examining nanoparticles in terms to their environmental and biological effects and implications. In this study, the effects of a water-soluble hyper-harmonized hydroxyl-modified fullerene (3HFWC) on cherry tomato seed germination, seedlings growth, physiological response and fruiting was evaluated. Changes in the photosynthetic pigments content, oxidative stress assessment, and aquaporin genes expression in cherry tomato plants were studied after during short- and long-term continuous exposure to 3HFWC nanosubstance (200 mg/L). Increased levels of photosynthetic pigments in leaves, lycopene in fruits, decreased levels of hydrogen peroxide content, activation of cellular antioxidant enzymes such as superoxide dismutase, catalase and peroxidase and increased aquaporin gene expression (PIP1;3, PIP1;5 and PIP2;4) were observed in 3HFWC nanosubstance-exposed plants in comparison to control, untreated cherry tomato plants. The 3HFWC nanosubstance showed positive effects on cherry tomato seed germination, plantlet growth and lycopene content in fruits and may be considered as a promising nanofertilizer.
Few-Shot Learning for Plant-Disease Recognition in the Frequency Domain
Authors: Lin Hong , Tse Rita , Tang Su-Kit , Qiang Zhenping , Pau Giovanni
Published: October 2022

Few-shot learning (FSL) is suitable for plant-disease recognition due to the shortage of data. However, the limitations of feature representation and the demanding generalization requirements are still pressing issues that need to be addressed. The recent studies reveal that the frequency representation contains rich patterns for image understanding. Given that most existing studies based on image classification have been conducted in the spatial domain, we introduce frequency representation into the FSL paradigm for plant-disease recognition. A discrete cosine transform module is designed for converting RGB color images to the frequency domain, and a learning-based frequency selection method is proposed to select informative frequencies. As a post-processing of feature vectors, a Gaussian-like calibration module is proposed to improve the generalization by aligning a skewed distribution with a Gaussian-like distribution. The two modules can be independent components ported to other networks. Extensive experiments are carried out to explore the configurations of the two modules. Our results show that the performance is much better in the frequency domain than in the spatial domain, and the Gaussian-like calibrator further improves the performance. The disease identification of the same plant and the cross-domain problem, which are critical to bring FSL to agricultural industry, are the research directions in the future.
Activity of Aqueous Extracts from Native Plants of the Yucatan Peninsula against Fungal Pathogens of Tomato In Vitro and from Croton chichenensis against Corynespora cassiicola on Tomato
Authors: Moo-Koh Felicia Amalia , Cristóbal-Alejo Jairo , Tun-Suárez José María , Medina-Baizabal Irma Leticia , Arjona-Cruz Alejandra Anahi , Gamboa-Angulo Marcela
Published: October 2022

Plant extracts are a valuable alternative to control pathogens of horticultural crops. In the present study, four species of pathogenic fungi were isolated from leaf spots on Solanum lycopersicum and identified by traditional and molecular techniques as Alternaria alternata ITC24, Corynespora cassiicola ITC23, Curvularia lunata ITC22, and Fusarium equiseti ITC32. When 11 aqueous extracts from eight native plants of the Yucatan Peninsula were tested against the four fungi in vitro, the extract from Croton chichenensis roots was most active, inhibiting mycelial growth (79–100%), sporulation (100%), and conidial germination (71–100%) at 3% (w/v). A logarithmic–diagrammatic scale of the pathosystem C. cassiicola–S. lycopersicum was established and used to assess disease severity on inoculated tomato plants in a greenhouse after treatment with the aqueous extract from C. chichenensis roots at 12% (w/v). After 21 days, the disease severity was 57% lower than on the control without extract applied. This dose of the extract was not phytotoxic to tomato leaves and was compatible with the beneficial organisms Bacillus subtilis CBCK47 and Trichodema asperellum Ta13-17. The antifungal efficacy of C. chichenensis is highly promising for incorporation into integrated disease management of tomato crops.