bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammation in Relation to Sarcopenia and Sarcopenic Obesity among Older Adults Living with Chronic Comorbidities: Results from the National Health and Nutrition Examination Survey 1999–2006
Authors: Karanth Shama D. , Washington Caretia , Cheng Ting-Yuan D. , Zhou Daohong , Leeuwenburgh Christiaan , Braithwaite Dejana , Zhang Dongyu
Published: November 2021

Loss of muscle mass and waning in muscle strength are common in older adults, and inflammation may play a key role in pathogenesis. This study aimed to examine associations of C-reactive protein (CRP) and systemic immune-inflammation index (SII) with sarcopenia and sarcopenic obesity in older adults with chronic comorbidities. Cross-sectional data from the National Health and Nutrition Examination Survey (1999–2006) were obtained for participants aged ≥60 years. Sarcopenia was defined by a lean mass and body height (males < 7.26 kg/m2, females < 5.45 kg/m2). Sarcopenic obesity was defined by the concurrent presence of sarcopenia and obesity (defined by relative fat mass). Logistic regression was used to assess the associations of CRP and SII with sarcopenia and sarcopenic obesity. The dose–response relationship was examined via restricted cubic splines. Of the participants (n = 2483), 23.1% (n = 574) and 7.7% (n = 190) had sarcopenia and sarcopenic obesity, respectively. The multivariable logistic regression models suggested a positive association of SII with sarcopenia and sarcopenic obesity, but a positive statistically significant association was not consistently observed for CRP. Dose–response curves suggested similar association patterns for these biomarkers. In clinical practice, measures to prevent sarcopenia and sarcopenic obesity are needed for older vulnerable people with high systemic inflammation.
The Effects of TRX Suspension Training Combined with Taurine Supplementation on Body Composition, Glycemic and Lipid Markers in Women with Type 2 Diabetes
Authors: Samadpour Masouleh Shohreh , Bagheri Reza , Ashtary-Larky Damoon , Cheraghloo Neda , Wong Alexei , Yousefi Bilesvar Omid , Suzuki Katsuhiko , Siahkouhian Marefat
Published: November 2021

Background: We aimed to investigate the effects of an 8-week total-body resistance exercise (TRX) suspension training intervention combined with taurine supplementation on body composition, blood glucose, and lipid markers in T2D females. Methods: Forty T2D middle-aged females (age: 53 ± 5 years, body mass = 84.3 ± 5.1 kg) were randomly assigned to four groups, TRX suspension training + placebo (TP; n = 10), TRX suspension training + taurine supplementation (TT; n = 10), taurine supplementation (T; n = 10), or control (C; n = 10). Body composition (body mass, body mass index (BMI), body fat percentage (BFP)), blood glucose (fasting blood sugar (FBS)), hemoglobin A1c (HbA1c), Insulin, and Insulin resistance (HOMA-IR), and lipid markers (low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG), and total cholesterol (TC)) were evaluated prior to and after interventions. Results: All three interventions significantly decreased body mass, BMI, and BFP with no changes between them for body mass and BMI; however, BFP changes in the TT group were significantly greater than all other groups. FBS was significantly reduced in TP and TT. Insulin concentrations’ decrement were significantly greater in all experimental groups compared to C; however, no between group differences were observed between TT, TP, and T. In regards to HOMA-IR, decreases in TT were significantly greater than all other groups TG, HbA1c, and LDL were reduced following all interventions. HDL values significantly increased only in the TT group, while TC significantly decreased in TP and TT groups. Changes in HbA1c, TG, HDL, and TC were significantly greater in the TT compared to all other groups. Conclusions: TRX training improved glycemic and lipid profiles, while taurine supplementation alone failed to show hypoglycemic and hypolipidemic properties. Notably, the synergic effects of TRX training and taurine supplementation were shown in HbA1c, HOMA-IR, TG, TC, HDL, and BFP changes. Our outcomes suggest that TRX training + taurine supplementation may be an effective adjuvant therapy in individuals with T2D.
Length of Nutritional Transition Associates Negatively with Postnatal Growth in Very Low Birthweight Infants
Authors: Immeli Lotta , Sankilampi Ulla , Mäkelä Pauliina M. , Leskinen Markus , Sund Reijo , Andersson Sture , Luukkainen Päivi
Published: November 2021

Very low birthweight (VLBW, <1500 g) infants may be predisposed to undernutrition during the nutritional transition phase from parenteral to enteral nutrition. We studied the associations among the length of the transition phase, postnatal macronutrient intake, and growth from birth to term equivalent age in VLBW infants. This retrospective cohort study included 248 VLBW infants born before 32 weeks of gestation and admitted to the Children’s Hospital, Helsinki, Finland during 2005–2013. Daily nutrient intakes were obtained from computerized medication administration records. The length of the transition phase correlated negatively with cumulative energy, protein, fat, and carbohydrate intake at 28 days of age. It also associated negatively with weight and head circumference growth from birth to term equivalent age. For infants with a long transition phase (over 12 d), the estimates (95% CI) for weight and head circumference z-score change from birth to term equivalent age were −0.3 (−0.56, −0.04) and −0.44 (−0.81, −0.07), respectively, in comparison to those with a short transition phase (ad 7 d). For VLBW infants, rapid transition to full enteral feeding might be beneficial. However, if enteral nutrition cannot be advanced, well-planned parenteral nutrition during the transition phase is necessary to promote adequate growth.
Energy Expenditure, Protein Oxidation and Body Composition in a Cohort of Very Low Birth Weight Infants
Authors: Perrone Michela , Menis Camilla , Piemontese Pasqua , Tabasso Chiara , Mallardi Domenica , Orsi Anna , Amato Orsola , Liotto Nadia , Roggero Paola , Mosca Fabio
Published: November 2021

The nutritional management of preterm infants is a critical point of care, especially because of the increased risk of developing extrauterine growth restriction (EUGR), which is associated with worsened health outcomes. Energy requirements in preterm infants are simply estimated, so the measurement of resting energy expenditure (REE) should be a key point in the nutritional evaluation of preterm infants. Although predictive formulae are available, it is well known that they are imprecise. The aim of our study was the evaluation of REE and protein oxidation (Ox) in very low birth weight infants (VLBWI) and the association with the mode of feeding and with body composition at term corrected age. Methods: Indirect calorimetry and body composition were performed at term corrected age in stable very low birth weight infants. Urinary nitrogen was measured in spot urine samples to calculate Ox. Infants were categorized as prevalent human milk (HMF) or prevalent formula diet (PFF). Results: Fifty VLBWI (HMF: 23, PFF: 27) were evaluated at 36.48 ± 0.85 post-conceptional weeks. No significant differences were found in basic characteristics or nutritional intake in the groups at birth and at the assessment. No differences were found in the REE of HMF vs. PFF (59.69 ± 9.8 kcal/kg/day vs. 59.27 ± 13.15 kcal/kg/day, respectively). We found statistical differences in the protein-Ox of HMF vs. PFF (1.7 ± 0.92 g/kg/day vs. 2.8 ± 1.65 g/kg/day, respectively, p < 0.01), and HMF infants had a higher fat-free mass (kg) than PFF infants (2.05 ± 0.26 kg vs. 1.82 ± 0.35 kg, respectively, p < 0.01), measured with air displacement plethysmography. Conclusion: REE is similar in infants with a prevalent human milk diet and in infants fed with formula. The HMF infants showed a lower oxidation rate of proteins for energy purposes and a better quality of growth. A greater amount of protein in HMF is probably used for anabolism and fat-free mass deposition. Further studies are needed to confirm our hypothesis.
Effects of Periodic Religious Fasting for Decades on Nutrient Intakes and the Blood Biochemical Profile
Authors: Petridou Anatoli , Rodopaios Nikolaos E. , Mougios Vassilis , Koulouri Alexandra-Aikaterini , Vasara Eleni , Papadopoulou Sousana K. , Skepastianos Petros , Hassapidou Maria , Kafatos Anthony
Published: November 2021

The aim of the present study was to examine differences and correlations in nutrient intakes and serum parameters related to nutrient intake (lipid profile, vitamins, and trace elements) in 200 lifelong Christian Orthodox Church (COC) fasters with periodic abstinence from certain foods (predominantly of animal origin) for approximately half of the year and 200 non-fasting controls, all of whom did not take dietary supplements. Nutrient intakes were assessed through three-day dietary recalls. Blood samples were drawn for the analysis of potential biomarkers of nutrient intake. Fasters had lower energy intake, due to lower fat and protein intake, compared to non-fasters (p < 0.05). Fasters also had lower intakes of vitamins A, B1, B2, B6, B12, D, folate, pantothenate, sodium, calcium, zinc, and phosphorus. Most participants (in both groups) did not meet the recommended dietary allowances of most vitamins and elements. Most serum biochemical parameters did not reflect the differences in nutrient intakes between groups, and none exhibited a correlation coefficient above 0.5 with nutrient intakes. Our findings suggest that COC fasting is associated with reduced intake of many nutrients, although this does not seem to have an impact on the blood biochemical profile.
Long-Term Evolution of Malnutrition and Loss of Muscle Strength after COVID-19: A Major and Neglected Component of Long COVID-19
Authors: Gérard Marine , Mahmutovic Meliha , Malgras Aurélie , Michot Niasha , Scheyer Nicolas , Jaussaud Roland , Nguyen-Thi Phi-Linh , Quilliot Didier
Published: November 2021

Post-acute consequences of COVID-19, also termed long COVID, include signs and symptoms persisting for more than 12 weeks with prolonged multisystem involvement; most often, however, malnutrition is ignored. Method: The objective was to analyze persistent symptoms, nutritional status, the evolution of muscle strength and performance status (PS) at 6 months post-discharge in a cohort of COVID-19 survivors. Results: Of 549 consecutive patients hospitalized for COVID-19 between 1 March and 29 April 2020, 23.7% died and 288 patients were at home at D30 post-discharge. At this date, 136 of them (47.2%) presented persistent malnutrition, a significant decrease in muscle strength or a PS ≥ 2. These patients received dietary counseling, nutritional supplementation, adapted physical activity guidance or physiotherapy assistance, or were admitted to post-care facilities. At 6 months post-discharge, 91.0% of the 136 patients (n = 119) were evaluated and 36.0% had persistent malnutrition, 14.3% complained of a significant decrease in muscle strength and 14.9% had a performance status > 2. Obesity was more frequent in patients with impairment than in those without (52.8% vs. 31.0%; p = 0.0071), with these patients being admitted more frequently to ICUs (50.9% vs. 31.3%; p = 0.010). Among those with persistent symptoms, 10% had psychiatric co-morbidities (mood disorders, anxiety, or post-traumatic stress syndrome), 7.6% had prolonged pneumological symptoms and 4.2% had neurological symptoms. Conclusions: Obese subjects as well as patients who have stayed in intensive care have a higher risk of functional loss or undernutrition 6 months after a severe COVID infection. Malnutrition and loss of muscle strength should be considered in the clinical assessment of these patients.
Differences in Dietary Patterns among the Polish Elderly: A Challenge for Public Health
Authors: Gajda Robert , Jeżewska-Zychowicz Marzena , Raczkowska Ewa
Published: November 2021

The aim of the study was to assess the diversity of dietary patterns within the elderly, in relation to the region of residence, household structure, and socioeconomic status. The questionnaire was conducted in a group of 427 Polish adults aged 60 and older from June to September 2019. The sample was selected by means of the snowball method in two regions. Principal component analysis (PCA) was used to extract and identify three dietary patterns (factors) from the frequency of eating 32 groups of foods. Logistic regression analysis was used to determine the relationship between the identified dietary patterns (DPs), region, household status, and socioeconomic index (SES). Adherence to the identified DPs, i.e., traditional, prudent, and adverse, was associated with socioeconomic status (SES) and living environment, i.e., living alone, with partner, or with family, while the region did not differentiate them. Less people living with their family were characterized by the frequent consumption of traditional food (the upper tertile of this DP), while more of them often consumed food that was typical for both prudent and adverse DPs (the upper tertiles of these DPs). The presence of a partner when living with family did not differentiate the adherence to DPs. A high SES decreased the chances of adhering to the upper tertiles of the “prudent” and “traditional” DPs, while living with family increased the chances of adhering to both the upper and middle tertiles of the “prudent” DP. Identifying the dietary patterns of the elderly contributes to a better understanding of the food intake of the senior citizens living in different social situations, in order to support public policies and nutritional counseling among this age group.
Sustained Antiviral and Liver Protection by a Nasal Therapeutic Vaccine (NASVAC, Containing Both HBsAg and HBcAg) in Patients with Chronic Hepatitis B: 2-Year Follow-Up of Phase III Clinical Trial
Authors: Akbar Sheikh Mohammad Fazle , Al Mahtab Mamun , Aguilar Julio Cesar , Yoshida Osamu , Penton Eduardo , Gerardo Guillen Nieto , Hiasa Yoichi
Published: November 2021

A phase III clinical trial in treatment-naïve patients with chronic hepatitis B (CHB) revealed the safety and considerable therapeutic efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (NASVAC) at the end of treatment (EOT) and 24 weeks after EOT. Two years after EOT, we checked HBV DNA, alanine aminotransferase (ALT), and hepatitis B e antigen (HBeAg). The data reveal that 33 of 66 NASVAC-recipient CHB patients became negative for HBV DNA in the blood two years after EOT. The ALT levels were within the upper limit of normal (ULN) in 37 patients, although all 66 CHB patients had elevated ALT (above ULN) before the start of therapy. Out of the total twelve HBeAg-positive patients, eight patients became negative for HBeAg. None of the patients developed cirrhosis of the liver within this period. NASVAC is a finite treatment regimen with sustained antiviral and liver-protecting properties. This study is the first to report follow-up data of immune therapy for CHB. NASVAC, an immune therapy of finite duration, is endowed with sustained antiviral and liver protection properties in CHB patients.
Transplacental Antibody Transfer of Respiratory Syncytial Virus Specific IgG in Non-Human Primate Mother-Infant Pairs
Authors: Citron Michael P. , McAnulty Jessica , Callahan Cheryl , Knapp Walter , Fontenot Jane , Morales Pablo , Flynn Jessica A. , Douglas Cameron M. , Espeseth Amy S.
Published: November 2021

One approach to protect new-borns against respiratory syncytial virus (RSV) is to vaccinate pregnant women in the last trimester of pregnancy. The boosting of circulating antibodies which can be transferred to the foetus would offer immune protection against the virus and ultimately the disease. Since non-human primates (NHPs) have similar reproductive anatomy, physiology, and antibody architecture and kinetics to humans, we utilized this preclinical species to evaluate maternal immunization (MI) using an RSV F subunit vaccine. Three species of NHPs known for their ability to be infected with human RSV in experimental challenge studies were tested for RSV-specific antibodies. African green monkeys had the highest overall antibody levels of the old-world monkeys evaluated and they gave birth to offspring with anti-RSV titers that were proportional to their mother. These higher overall antibody levels are associated with greater durability found in their offspring. Immunization of RSV seropositive AGMs during late pregnancy boosts RSV titers, which consequentially results in significantly higher titers in the vaccinated new-borns compared to the new-borns of unvaccinated mothers. These findings, accomplished in small treatment group sizes, demonstrate a model that provides an efficient, resource sparing and translatable preclinical in vivo system for evaluating vaccine candidates for maternal immunization.
Survival of Enterohemorrhagic Escherichia coli O104:H4 Strain C227/11Φcu in Agricultural Soils Depends on rpoS and Environmental Factors
Authors: Detert Katharina , Schmidt Herbert
Published: November 2021

The consumption of contaminated fresh produce caused outbreaks of enterohemorrhagic (EHEC) Escherichia coli. Agricultural soil might be a reservoir for EHEC strains and represent a contamination source for edible plants. Furthermore, the application of manure as fertilizer is an important contamination route. Thus, the German fertilizer ordinance prohibits the use of manure 12 weeks before crop harvest to avoid pathogen transmission into the food chain. In this study, the survival of E. coli O104:H4 strain C227/11Φcu in soil microenvironments with either diluvial sand or alluvial loam at two temperatures was investigated for more than 12 weeks. It was analyzed whether the addition of cattle manure extends EHEC survival in these microenvironments. The experiments were additionally performed with isogenic ΔrpoS and ΔfliC deletion mutants of C227/11Φcu. The survival of C227/11Φcu was highest at 4 °C, whereas the soil type had a minor influence. The addition of cattle manure increased the survival at 22 °C. Deletion of rpoS significantly decreased the survival period under all cultivation conditions, whereas fliC deletion did not have any influence. The results of our study demonstrate that EHEC C227/11Φcu is able to survive for more than 12 weeks in soil microenvironments and that RpoS is an important determinant for survival.
Characterisation of Macrophage Polarisation in Mice Infected with Ninoa Strain of Trypanosoma cruzi
Authors: Medina-Buelvas Dunia M. , Rodríguez-Sosa Miriam , Vega Libia
Published: November 2021

Macrophages (MΦ) play a key role in the development of the protective immune response against Trypanosoma cruzi infection. To determine the role of MΦ subtypes M1 and M2 in the development of immunity against the Mexican strain of T. cruzi (Ninoa strain), we have analysed in a time course the infection and characterised the M1 and M2 subtypes in two mouse models, BALB/c and C57BL/6. After infection, BALB/c mice developed an increased blood parasite load and the parasites were cleared from the blood one week later than in C57BL/6 mice. However, similar cellular infiltrate and cardiac alterations were observed between BALB/c and C57BL/6 mice. At 36 days, the T. cruzi infection differentially modulated the expression of immune cells, and both the BALB/c and C57BL/6 mice significantly reduced TCD4+ cells. However, BALB/c mice produced significantly more TCD8+ than C57BL/6 mice in the spleen and lymph nodes. Furthermore, BALB/c mice produce significantly more MΦ in the spleen, while C57BL/6 produce similar levels to uninfected mice. The M1 MΦ ratio increased significantly at 3–5 days post-infection (dpi), but then decreased slightly. On the contrary, the M2 MΦ were low at the beginning of the infection, but the proportion of M1 and M2 MΦ at 36 dpi was similar. Importantly, the MΦ subtypes M2c and M2d significantly increased the induction of tissue repair by the end of the acute phase of the infection. These results indicate that the Ninoa strain has developed strategies to modulate the immune response, with fine differences depending on the genetic background of the host.
Alleviation of Androgenetic Alopecia with Aqueous Paeonia lactiflora and Poria cocos Extract Intake through Suppressing the Steroid Hormone and Inflammatory Pathway
Authors: Zhang Ting , Cao Shihua , Yuan Heng , Park Sunmin
Published: November 2021

Paeonia lactiflora Pallas (PL) and Poria cocos Wolf (PC) have been traditionally used to treat inflammatory diseases reported in Dongui Bogam and Shen Nong Ben Cao Jing, traditional medical books in Korean and China, respectively. We determined the efficacies and the molecular mechanisms of PL, PC, and PL + PC aqueous extracts on androgenetic alopecia (AGA) induced by testosterone propionate in C57BL/6 mice. The molecular mechanisms of PL and PC in AGA treatment were examined using experimental assays and network pharmacology. The AGA model was generated by topically applying 0.5% testosterone propionate in 70% ethanol solution to the backs of mice daily for 28 days while the normal-control (Normal-Con; no AGA induction) mice applied 70% ethanol. The 0.1% PL (AGA-PL), 0.1% PC (AGA-PC), 0.05% PL + 0.05% PC (AGA-MIX), and 0.1% cellulose (AGA-Con; control) were supplemented in a high-fat diet for 28 days in AGA-induced mice. Positive-control (AGA-Positive) were administered 2% finasteride daily on the backs of the AGA mice. Hair growth rates decreased in the order of AGA-PL, AGA-MIX, AGA-PC, AGA-Positive, and AGA-Con after 21 days of treatment (ED21). On ED28, skins were completely covered with hair in the AGA-PL and AGA-MIX groups. Serum testosterone concentrations were lower in the AGA-PL group than in the AGA-Con group and similar to concentrations in the Normal-Con group, whereas serum 17β-estradiol concentrations showed the opposite pattern with increasing aromatase mRNA expression (p < 0.05). In the dorsal skin, DKK1 and NR3C2 mRNA expressions were significantly lower, but TGF-β2, β-Catenin, and PPARG expressions were higher in the AGA-PL and AGA-PC groups than in the AGA-Con group (p < 0.05), whereas TNF-α and IL-6 mRNA expressions were lower in the AGA-PL, AGA-MIX, and Normal-Con groups than in the AGA-Con group (p < 0.05). The phosphorylation of Akt and GSK-3β in the dorsal skin was lower in AGA-Con than normal-Con, and PL and MIX ingestion suppressed their decrease similar to the Normal-Con. In conclusion, PL or PL + PC intake had beneficial effects on hair growth similar to Normal-Con. The promotion was related to lower serum testosterone concentrations and pro-inflammatory cytokine levels, and inhibition of the steroid hormone pathway, consistent with network pharmacology analysis findings.
The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-Candida Activity by Damaging Cell Membrane Integrity
Authors: Babii Cornelia , Savu Mihaela , Motrescu Iuliana , Birsa Lucian Mihail , Sarbu Laura Gabriela , Stefan Marius
Published: November 2021

Infections caused by Candida are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with Candida infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four Candida clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against C. albicans, C. parapsilosis, C. krusei and C. glabrata. The investigation of anti-Candida mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against Candida spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against C. albicans strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of Candida spp. multidrug resistance phenomenon.
Exosome-Mediated Insulin Delivery for the Potential Treatment of Diabetes Mellitus
Authors: Rodríguez-Morales Belén , Antunes-Ricardo Marilena , González-Valdez José
Published: November 2021

Exosomes are extracellular nanovesicles between 30 and 150 nm that serve as essential messengers for different biological signaling and pathological processes. After their discovery, a wide range of applications have been developed, especially in therapeutic drug delivery. In this context, the aim of this work was to test the efficiency of exosome-mediated human insulin delivery using exosomes extracted from three different cell lines: hepatocellular carcinoma (HepG2); primary dermal fibroblasts (HDFa) and pancreatic β cells (RIN-m); all are related to the production and/or the ability to sense insulin and to consequently regulate glucose levels in the extracellular medium. The obtained results revealed that the optimal insulin loading efficiency was achieved by a 200 V electroporation, in comparison with incubation at room temperature. Moreover, the maximum in vitro exosome uptake was reached after incubation for 6 h, which slightly decreased 24 h after adding the exosomes. Glucose quantification assays revealed that exosome-mediated incorporation of insulin presented significant differences in HDFa and HepG2 cells, enhancing the transport in HDFa, in comparison with free human insulin effects in the regulation of extracellular glucose levels. No significant differences were found between the treatments in RIN-m cells. Hence, the results suggest that exosomes could potentially become a valuable tool for stable and biocompatible insulin delivery in diabetes mellitus treatment alternatives.
Optimized In Silico Modeling of Drug Absorption after Gastric Bypass: The Case of Metformin
Authors: Dahan Arik , Porat Daniel , Markovic Milica , Zur Moran , Kister Olga , Langguth Peter
Published: November 2021

Bariatric surgery is an effective treatment for severe obesity and related comorbidities, such as type II diabetes. Gastric bypass surgery shortens the length of the intestine, possibly leading to altered drug absorption. Metformin, a first-line treatment for type II diabetes, has permeability-dependent drug absorption, which may be sensitive to intestinal anatomic changes during bypass surgery, including Roux-en-Y gastric bypass (RYGB). Previous computer simulation data indicate increased metformin absorption after RYGB. In this study, we experimentally determined the region-dependent permeability of metformin, using the rat single-pass intestinal perfusion method (SPIP), which we then implemented into GastroPlusTM to assess the contribution of our SPIP data to post-RYGB metformin absorption modeling. Previous simulations allowed a good fit with in vivo literature data on healthy and obese control subjects. However, it was revealed that for post-RYGB drug absorption predictions, simply excluding the duodenum/jejunum is insufficient, as the software underestimates the observed plasma concentrations post-RYGB. By implementing experimentally determined segmental-dependent permeabilities for metformin in the remaining segments post-surgery, GastroPlusTM proved to fit the observed plasma concentration profile, making it a useful tool for predicting drug absorption after gastric bypass. Reliable evaluation of the parameters dictating drug absorption is required for the accurate prediction of overall absorption after bariatric surgery.
Chitosan-Based Biocompatible Copolymers for Thermoresponsive Drug Delivery Systems: On the Development of a Standardization System
Authors: Marsili Lorenzo , Dal Bo Michele , Berti Federico , Toffoli Giuseppe
Published: November 2021

Chitosan is a natural polysaccharide that is considered to be biocompatible, biodegradable and non-toxic. The polymer has been used in drug delivery applications for its positive charge, which allows for adhesion with and recognition of biological tissues via non-covalent interactions. In recent times, chitosan has been used for the preparation of graft copolymers with thermoresponsive polymers such as poly-N-vinylcaprolactam (PNVCL) and poly-N-isopropylamide (PNIPAM), allowing the combination of the biodegradability of the natural polymer with the ability to respond to changes in temperature. Due to the growing interest in the utilization of thermoresponsive polymers in the biological context, it is necessary to increase the knowledge of the key principles of thermoresponsivity in order to obtain comparable results between different studies or applications. In the present review, we provide an overview of the basic principles of thermoresponsivity, as well as a description of the main polysaccharides and thermoresponsive materials, with a special focus on chitosan and poly-N-Vinyl caprolactam (PNVCL) and their biomedical applications.
Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design
Authors: Kejík Zdeněk , Kaplánek Robert , Dytrych Petr , Masařík Michal , Veselá Kateřina , Abramenko Nikita , Hoskovec David , Vašáková Martina , Králová Jarmila , Martásek Pavel , Jakubek Milan
Published: November 2021

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death. This review discusses the impact of NSCLC therapy strategies based on a meta-analysis of clinical studies. In addition, possible therapeutic strategies for repression when standard methods fail, such as the administration of low-toxicity natural anticancer agents targeting these phenomena (curcumin and flavonoids), are also discussed. These strategies are presented in the context of key mechanisms of tumour biology with a strong influence on CTC spread and metastasis (mechanisms related to tumour-associated and -infiltrating cells, epithelial–mesenchymal transition, and migration of cancer cells).
Microbial Fibrinolytic Enzymes as Anti-Thrombotics: Production, Characterisation and Prodigious Biopharmaceutical Applications
Authors: Sharma Chhavi , Osmolovskiy Alexander , Singh Rajni
Published: November 2021

Cardiac disorders such as acute myocardial infarction, embolism and stroke are primarily attributed to excessive fibrin accumulation in the blood vessels, usually consequential in thrombosis. Numerous methodologies including the use of anti-coagulants, anti-platelet drugs, surgical operations and fibrinolytic enzymes are employed for the dissolution of fibrin clots and hence ameliorate thrombosis. Microbial fibrinolytic enzymes have attracted much more attention in the management of cardiovascular disorders than typical anti-thrombotic strategies because of the undesirable after-effects and high expense of the latter. Fibrinolytic enzymes such as plasminogen activators and plasmin-like proteins hydrolyse thrombi with high efficacy with no significant after-effects and can be cost effectively produced on a large scale with a short generation time. However, the hunt for novel fibrinolytic enzymes necessitates complex purification stages, physiochemical and structural-functional attributes, which provide an insight into their mechanism of action. Besides, strain improvement and molecular technologies such as cloning, overexpression and the construction of genetically modified strains for the enhanced production of fibrinolytic enzymes significantly improve their thrombolytic potential. In addition, the unconventional applicability of some fibrinolytic enzymes paves their way for protein hydrolysis in addition to fibrin/thrombi, blood pressure regulation, anti-microbials, detergent additives for blood stain removal, preventing dental caries, anti-inflammatory and mucolytic expectorant agents. Therefore, this review article encompasses the production, biochemical/structure-function properties, thrombolytic potential and other surplus applications of microbial fibrinolytic enzymes.
Supramolecular Surface Functionalization of Iron Oxide Nanoparticles with α-Cyclodextrin-Based Cationic Star Polymer for Magnetically-Enhanced Gene Delivery
Authors: Li Hanyi , Peng Erwin , Zhao Feng , Li Jun , Xue Junmin
Published: November 2021

Supramolecular polymers formed through host–guest complexation have inspired many interesting developments of functional materials for biological and biomedical applications. Here, we report a novel design of a non-viral gene delivery system composed of a cationic star polymer forming supramolecular complexes with the surface oleyl groups of superparamagnetic iron oxide nanoparticles (SPIONs), for magnetically enhanced delivery of DNA into mammalian cells. The cationic star polymer was synthesized by grafting multiple oligoethylenimine (OEI) chains onto an α-cyclodextrin (α-CD) core. The SPIONs were synthesized from iron(III) acetylacetonate and stabilized by hydrophobic oleic acid and oleylamine in hexane, which were characterized in terms of their size, structure, morphology, and magnetic properties. The synthesized magnetic particles were found to be superparamagnetic, making them a suitable ferrofluid for biological applications. In order to change the hydrophobic surface of the SPIONs to a hydrophilic surface with functionalities for plasmid DNA (pDNA) binding and gene delivery, a non-traditional but simple supramolecular surface modification process was used. The α-CD-OEI cationic star polymer was dissolved in water and then mixed with the SPIONs stabilized in hexane. The SPIONs were “pulled” into the water phase through the formation of supramolecular host–guest inclusion complexes between the α-CD unit and the oleyl surface of the SPIONs, while the surface of the SPIONs was changed to OEI cationic polymers. The α-CD-OEI-SPION complex could effectively bind and condense pDNA to form α-CD-OEI-SPION/pDNA polyplex nanoparticles at the size of ca. 200 nm suitable for delivery of genes into cells through endocytosis. The cytotoxicity of the α-CD-OEI-SPION complex was also found to be lower than high-molecular-weight polyethylenimine, which was widely studied previously as a standard non-viral gene vector. When gene transfection was carried out in the presence of an external magnetic field, the α-CD-OEI-SPION/pDNA polyplex nanoparticles greatly increased the gene transfection efficiency by nearly tenfold. Therefore, the study has demonstrated a facile two-in-one method to make the SPIONs water-soluble as well as functionalized for enhanced magnetofection.
Status Quo and Trends of Intra-Arterial Therapy for Brain Tumors: A Bibliometric and Clinical Trials Analysis
Authors: Rechberger Julian S. , Thiele Frederic , Daniels David J.
Published: November 2021

Intra-arterial drug delivery circumvents the first-pass effect and is believed to increase both efficacy and tolerability of primary and metastatic brain tumor therapy. The aim of this update is to report on pertinent articles and clinical trials to better understand the research landscape to date and future directions. Elsevier’s Scopus and ClinicalTrials.gov databases were reviewed in August 2021 for all possible articles and clinical trials of intra-arterial drug injection as a treatment strategy for brain tumors. Entries were screened against predefined selection criteria and various parameters were summarized. Twenty clinical trials and 271 articles satisfied all inclusion criteria. In terms of articles, 201 (74%) were primarily clinical and 70 (26%) were basic science, published in a total of 120 different journals. Median values were: publication year, 1986 (range, 1962–2021); citation count, 15 (range, 0–607); number of authors, 5 (range, 1–18). Pertaining to clinical trials, 9 (45%) were phase 1 trials, with median expected start and completion years in 2011 (range, 1998–2019) and 2022 (range, 2008–2025), respectively. Only one (5%) trial has reported results to date. Glioma was the most common tumor indication reported in both articles (68%) and trials (75%). There were 215 (79%) articles investigating chemotherapy, while 13 (65%) trials evaluated targeted therapy. Transient blood–brain barrier disruption was the commonest strategy for articles (27%) and trials (60%) to optimize intra-arterial therapy. Articles and trials predominately originated in the United States (50% and 90%, respectively). In this bibliometric and clinical trials analysis, we discuss the current state and trends of intra-arterial therapy for brain tumors. Most articles were clinical, and traditional anti-cancer agents and drug delivery strategies were commonly studied. This was reflected in clinical trials, of which only a single study had reported outcomes. We anticipate future efforts to involve novel therapeutic and procedural strategies based on recent advances in the field.
Biomimetic Nanoparticles Coated with Bacterial Outer Membrane Vesicles as a New-Generation Platform for Biomedical Applications
Authors: Naskar Atanu , Cho Hyejin , Lee Sohee , Kim Kwang-sun
Published: November 2021

The biomedical field is currently reaping the benefits of research on biomimetic nanoparticles (NPs), which are synthetic nanoparticles fabricated with natural cellular materials for nature-inspired biomedical applications. These camouflage NPs are capable of retaining not only the physiochemical properties of synthetic nanoparticles but also the original biological functions of the cellular materials. Accordingly, NPs coated with cell-derived membrane components have achieved remarkable growth as prospective biomedical materials. Particularly, bacterial outer membrane vesicle (OMV), which is a cell membrane coating material for NPs, is regarded as an important molecule that can be employed in several biomedical applications, including immune response activation, cancer therapeutics, and treatment for bacterial infections with photothermal activity. The currently available cell membrane-coated NPs are summarized in this review. Furthermore, the general features of bacterial OMVs and several multifunctional NPs that could serve as inner core materials in the coating strategy are presented, and several methods that can be used to prepare OMV-coated NPs (OMV-NPs) and their characterization are highlighted. Finally, some perspectives of OMV-NPs in various biomedical applications for future potential breakthrough are discussed. This in-depth review, which includes potential challenges, will encourage researchers to fabricate innovative and improvised, new-generation biomimetic materials through future biomedical applications.
Two Is Company, but Four Is a Party—Challenges of Tetraploidization for Cell Wall Dynamics and Efficient Tip-Growth in Pollen
Authors: Westermann Jens
Published: November 2021

Some cells grow by an intricately coordinated process called tip-growth, which allows the formation of long tubular structures by a remarkable increase in cell surface-to-volume ratio and cell expansion across vast distances. On a broad evolutionary scale, tip-growth has been extraordinarily successful, as indicated by its recurrent ‘re-discovery’ throughout evolutionary time in all major land plant taxa which allowed for the functional diversification of tip-growing cell types across gametophytic and sporophytic life-phases. All major land plant lineages have experienced (recurrent) polyploidization events and subsequent re-diploidization that may have positively contributed to plant adaptive evolutionary processes. How individual cells respond to genome-doubling on a shorter evolutionary scale has not been addressed as elaborately. Nevertheless, it is clear that when polyploids first form, they face numerous important challenges that must be overcome for lineages to persist. Evidence in the literature suggests that tip-growth is one of those processes. Here, I discuss the literature to present hypotheses about how polyploidization events may challenge efficient tip-growth and strategies which may overcome them: I first review the complex and multi-layered processes by which tip-growing cells maintain their cell wall integrity and steady growth. I will then discuss how they may be affected by the cellular changes that accompany genome-doubling. Finally, I will depict possible mechanisms polyploid plants may evolve to compensate for the effects caused by genome-doubling to regain diploid-like growth, particularly focusing on cell wall dynamics and the subcellular machinery they are controlled by.
Mobile Biomonitoring of Atmospheric Pollution: A New Perspective for the Moss-Bag Approach
Authors: Sorrentino Maria Cristina , Capozzi Fiore , Wuyts Karen , Joosen Steven , Mubiana Valentine K. , Giordano Simonetta , Samson Roeland , Spagnuolo Valeria
Published: November 2021

In this work the potential of moving moss-bags, fixed to bicycles, to intercept particulate matter (PM) and linked metal(loid)s was tested for the first time. Seven volunteers carried three moss-bags for fifty days while commuting by bicycle in the urban area of Antwerp, Belgium. Moreover, one bike, equipped with mobile PM samplers, travelled along four routes: urban, industrial, green route and the total path, carrying three moss-bags at each route. The saturation isothermal remanent magnetization (SIRM) signal and chemical composition (assessed by HR-ICP-MS) of the moss samples indicated that the industrial route was the most polluted. Element fluxes (i.e., the ratio between element daily uptake and the specific leaf area) could discriminate among land uses; particularly, they were significantly higher in the industrial route for Ag, As, Cd and Pb; significantly lowest in the green route for As and Pb; and comparable for all accumulated elements along most urban routes. A comparison with a previous experiment carried out in the same study area using similar moss-bags at static exposure points, showed that the element fluxes were significantly higher in the mobile system. Finally, PM2.5 and PM10 masses measured along the four routes were consistent with element fluxes.
Is Your Moss Alive during Active Biomonitoring Study?
Authors: Świsłowski Paweł , Nowak Arkadiusz , Rajfur Małgorzata
Published: November 2021

Biomonitoring was proposed to assess the condition of living organisms or entire ecosystems with the use of bioindicators—species sensitive to specific pollutants. It is important that the bioindicator species remains alive for as long as possible while retaining the ability to react to the negative effects of pollution (elimination/neutralization of hazardous contaminants). The purpose of the study was to assess the survival of Pleurozium schreberi moss during exposure (moss-bag technique) based on the measurement of the concentration of elements (Ni, Cu, Zn, Cd, and Pb), chlorophyll content, and its fluorescence. The study was carried out using a CCM-300 portable chlorophyll content meter, portable fluorometer, UV-Vis spectrophotometer, and a flame atomic absorption spectrometer. As a result of the laboratory tests, no significant differences were found in the chlorophyll content in the gametophytes of mosses tested immediately after collection from the forest, compared to those drying at room temperature in the laboratory (p = 0.175 for Student’s t-test results). Mosses exposed using the moss-bag technique of active biomonitoring were characterized by a drop in the chlorophyll content over 12 weeks (more than 50% and 60% for chlorophyll-a and chlorophyll-b, respectively). Chlorophyll content in mosses during exposure was correlated with actual photochemical efficiency (yield) of photosystem II (calculated value of Pearson’s linear correlation coefficient was 0.94—there was a significant correlation between chlorophyll a and yield p = 0.02). The highest metal increases in mosses (RAF values) were observed for zinc, lead, and copper after the second and third month of exposure. The article demonstrates that the moss exposed in an urbanized area for a period of three months maintains the properties of good bioindicator of environmental quality.
Vitrification Ability of Combined and Single Cryoprotective Agents
Authors: Faltus Milos , Bilavcik Alois , Zamecnik Jiri
Published: November 2021

Cryoprotective agents (CPA) are an important part of many current vitrification methods. The vitrification ability of CPAs influences the probability of the glass transition and water crystallization occurrence. Thermal characteristics and the vitrification ability of two combined CPAs (PVS2 and PVS3), common plant vitrification solutions, and four single CPAs (ethylene glycol, DMSO, glycerol, and sucrose), the components of the mentioned PVSs, were evaluated utilizing a differential scanning calorimetry (DSC) during standard cooling/warming rates of 10 °C min−1. The effect of solute concentration on their vitrification ability was shown in the CPAs tested. Four typical concentration regions at which the glassy state and/or crystallization occurred were defined. We suggest the solute concentration of 0.7 g g−1 as the universal vitrification concentration, characterized by an actual Tg of CPA solution and limited water crystallization. Knowledge of the thermal properties of CPAs allows the design of new combined CPAs with the required vitrification ability respecting the cryopreservation method used and the characteristics of the cryopreserved sample.
Methods of In Situ Quantitative Root Biology
Authors: Pasternak Taras , Pérez-Pérez José Manuel
Published: November 2021

When dealing with plant roots, a multiscale description of the functional root structure is needed. Since the beginning of 21st century, new devices such as laser confocal microscopes have been accessible for coarse root structure measurements, including three-dimensional (3D) reconstruction. Most researchers are familiar with using simple 2D geometry visualization that does not allow quantitative determination of key morphological features from an organ-like perspective. We provide here a detailed description of the quantitative methods available for 3D analysis of root features at single-cell resolution, including root asymmetry, lateral root analysis, cell size and nuclear organization, cell-cycle kinetics, and chromatin structure analysis. Quantitative maps of the root apical meristem (RAM) are shown for different species, including Arabidopsis thaliana (L.), Heynh, Nicotiana tabacum L., Medicago sativa L., and Setaria italica (L.) P. Beauv. The 3D analysis of the RAM in these species showed divergence in chromatin organization and cell volume distribution that might be used to study root zonation for each root tissue. Detailed protocols and possible pitfalls in the usage of the marker lines are discussed. Therefore, researchers who need to improve their quantitative root biology portfolio can use them as a reference.