bluuebunny/crossref_metadata_2025 huggingface dataset:
Postoperative Dietary Intake Achievement: A Secondary Analysis of a Randomized Controlled Trial
Authors: Ho Chiou Yi , Ibrahim Zuriati , Abu Zaid Zalina , Mat Daud Zulfitri Azuan , Mohd Yusop Nor Baizura , Mohd Abas Mohd Norazam , Omar Jamil
Published: January 2022

Sufficient postoperative dietary intake is crucial for ensuring a better surgical outcome. This study aimed to investigate the postoperative dietary intake achievement and predictors of postoperative dietary intake among gynecologic cancer patients. A total of 118 participants were included in this secondary analysis. Postoperative dietary data was pooled and re-classified into early postoperative dietary intake achievement (EDIA) (daily energy intake (DEI) ≥ 75% from the estimated energy requirement (EER)) and delay dietary intake achievement (DDIA) (DEI < 75% EER) There was a significant difference in postoperative changes in weight (p = 0.002), muscle mass (p = 0.018), and handgrip strength (p = 0.010) between the groups. Postoperative daily energy and protein intake in the EDIA was significantly greater than DDIA from operation day to discharged (p = 0.000 and p = 0.036). Four significant independent postoperative dietary intake predictors were found: preoperative whey protein-infused carbohydrate loading (p = 0.000), postoperative nausea vomiting (p = 0.001), age (p = 0.010), and time to tolerate clear fluid (p = 0.016). The multilinear regression model significantly predicted postoperative dietary intake, F (4, 116) = 68.013, p = 0.000, adj. R2 = 0.698. With the four predictors’ recognition, the integration of a more specific and comprehensive dietitian-led supportive care with individualized nutrition intervention ought to be considered to promote functional recovery.
Protective Effect of Probiotics Isolated from Traditional Fermented Tea Leaves (Miang) from Northern Thailand and Role of Synbiotics in Ameliorating Experimental Ulcerative Colitis in Mice
Authors: Kangwan Napapan , Kongkarnka Sarawut , Boonkerd Nitsara , Unban Kridsada , Shetty Kalidas , Khanongnuch Chartchai
Published: January 2022

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.
Capsaicin and Its Effect on Exercise Performance, Fatigue and Inflammation after Exercise
Authors: Giuriato Gaia , Venturelli Massimo , Matias Alexs , Soares Edgard M. K. V. K. , Gaetgens Jessica , Frederick Kimberley A. , Ives Stephen J.
Published: January 2022

Capsaicin (CAP) activates the transient receptor potential vanilloid 1 (TRPV1) channel on sensory neurons, improving ATP production, vascular function, fatigue resistance, and thus exercise performance. However, the underlying mechanisms of CAP-induced ergogenic effects and fatigue-resistance, remain elusive. To evaluate the potential anti-fatigue effects of CAP, 10 young healthy males performed constant-load cycling exercise time to exhaustion (TTE) trials (85% maximal work rate) after ingestion of placebo (PL; fiber) or CAP capsules in a blinded, counterbalanced, crossover design, while cardiorespiratory responses were monitored. Fatigue was assessed with the interpolated twitch technique, pre-post exercise, during isometric maximal voluntary contractions (MVC). No significant differences (p > 0.05) were detected in cardiorespiratory responses and self-reported fatigue (RPE scale) during the time trial or in TTE (375 ± 26 and 327 ± 36 s, respectively). CAP attenuated the reduction in potentiated twitch (PL: −52 ± 6 vs. CAP: −42 ± 11%, p = 0.037), and tended to attenuate the decline in maximal relaxation rate (PL: −47 ± 33 vs. CAP: −29 ± 68%, p = 0.057), but not maximal rate of force development, MVC, or voluntary muscle activation. Thus, CAP might attenuate neuromuscular fatigue through alterations in afferent signaling or neuromuscular relaxation kinetics, perhaps mediated via the sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) pumps, thereby increasing the rate of Ca2+ reuptake and relaxation.
The Intake of Phosphorus and Nitrites through Meat Products: A Health Risk Assessment of Children Aged 1 to 9 Years Old in Serbia
Authors: Milešević Jelena , Vranić Danijela , Gurinović Mirjana , Korićanac Vladimir , Borović Branka , Zeković Milica , Šarac Ivana , Milićević Dragan , Glibetić Maria
Published: January 2022

This study provides the data on dietary exposure of Serbian children to nitrites and phosphorus from meat products by combining individual consumption data with available analytical data of meat products. A total of 2603 and 1900 commercially available meat products were categorized into seven groups and analysed for nitrite and phosphorous content. The highest mean levels of nitrite content, expressed as NaNO2, were found in finely minced cooked sausages (40.25 ± 20.37 mg/kg), followed by canned meat (34.95 ± 22.12 mg/kg) and coarsely minced cooked sausages (32.85 ± 23.25 mg/kg). The EDI (estimated daily intake) of nitrites from meat products, calculated from a National Food Consumption Survey in 576 children aged 1–9 years, indicated that the Serbian children population exceeded the nitrite ADI (acceptable daily intake) proposed by EFSA (European Food Safety Authority) in 6.4% of children, with a higher proportion in 1–3-year-old participants. The mean phosphorus concentration varied from 2.71 ± 1.05 g/kg to 6.12 ± 1.33 g/kg in liver sausage and pate and smoked meat products, respectively. The EDI of phosphorus from meat products was far below the ADI proposed by EFSA, indicating that the use of phosphorus additives in Serbian meat products is generally in line with legislation.
Biological Role of Vitamin K—With Particular Emphasis on Cardiovascular and Renal Aspects
Authors: Stępień Anna , Koziarska-Rościszewska Małgorzata , Rysz Jacek , Stępień Mariusz
Published: January 2022

Vitamin K (VK) plays many important functions in the body. The most important of them include the contribution in calcium homeostasis and anticoagulation. Vascular calcification (VC) is one of the most important mechanisms of renal pathology. The most potent inhibitor of this process—matrix Gla protein (MGP) is VK-dependent. Chronic kidney disease (CKD) patients, both non-dialysed and hemodialysed, often have VK deficiency. Elevated uncarboxylated matrix Gla protein (ucMGP) levels indirectly reflected VK deficiency and are associated with a higher risk of cardiovascular events in these patients. It has been suggested that VK intake may reduce the VC and related cardiovascular risk. Vitamin K intake has been suggested to reduce VC and the associated cardiovascular risk. The role and possibility of VK supplementation as well as the impact of anticoagulation therapy on VK deficiency in CKD patients is discussed.
Preconception Hemoglobin Concentration and Risk of Low Birth Weight and Small-for-Gestational-Age: A Large Prospective Cohort Study in China
Authors: Liu Xiaojing , An Hang , Li Nan , Li Zhiwen , Zhang Yali , Zhang Le , Li Hongtian , Liu Jianmeng , Ye Rongwei
Published: January 2022

Less is known about the impact of maternal preconception anemia on birth outcomes. We aimed to examine associations between preconception hemoglobin (Hb) concentrations with risk of low birth weight (LBW) and small-for-gestational-age (SGA). This study was from a large population-based prospective cohort in China and included 124,725 women with singleton live births delivered at gestational ages of 28–45 weeks who were registered before pregnancy. Maternal Hb concentrations were measured during registration, and other health-related information was recorded prospectively. Logistic regression was used to evaluate the associations between preconception Hb concentrations with risk of LBW and SGA, adjusting for potential confounders. The results showed women with preconception anemia accounted for 22.28%. The incidences of LBW/SGA were 2.37%/6.30% among anemic women, and 2.01%/5.48% among non-anemic women, respectively. Preconception mild anemia increased by 17% (95% confidence interval (CI): 1.06, 1.28) and 14% (95% CI: 1.07, 1.21) the risk for LBW and SGA, while moderate-to-severe anemia had no significant association with LBW and SGA. Compared with the 120–129 g/L group, a U-shaped association was observed between preconception Hb concentrations with LBW and SGA. In conclusion, not only maternal anemia but also elevated Hb concentrations before pregnancy contribute to an increased risk of LBW and SGA.
Potential Neurocognitive Symptoms Due to Respiratory Syncytial Virus Infection
Authors: Andrade Catalina A. , Kalergis Alexis M. , Bohmwald Karen
Published: January 2022

Respiratory infections are among the major public health burdens, especially during winter. Along these lines, the human respiratory syncytial virus (hRSV) is the principal viral agent causing acute lower respiratory tract infections leading to hospitalization. The pulmonary manifestations due to hRSV infection are bronchiolitis and pneumonia, where the population most affected are infants and the elderly. However, recent evidence suggests that hRSV infection can impact the mother and fetus during pregnancy. Studies have indicated that hRSV can infect different cell types from the placenta and even cross the placenta barrier and infect the fetus. In addition, it is known that infections during the gestational period can lead to severe consequences for the development of the fetus due not only to a direct viral infection but also because of maternal immune activation (MIA). Furthermore, it has been described that the development of the central nervous system (CNS) of the fetus can be affected by the inflammatory environment of the uterus caused by viral infections. Increasing evidence supports the notion that hRSV could invade the CNS and infect nervous cells, such as microglia, neurons, and astrocytes, promoting neuroinflammation. Moreover, it has been described that the hRSV infection can provoke neurological manifestations, including cognitive impairment and behavioral alterations. Here, we will review the potential effect of hRSV in brain development and the potential long-term neurological sequelae.
Survey for ‘Candidatus Liberibacter’ and ‘Candidatus Phytoplasma’ in Citrus in Chile
Authors: Quiroga Nicolas , Gamboa Camila , Medina Gabriela , Contaldo Nicoletta , Torres Fernando , Bertaccini Assunta , Zamorano Alan , Fiore Nicola
Published: January 2022

The considerable economic losses in citrus associated with ‘Candidatus Liberibacter’ and ‘Candidatus Phytoplasma’ presence have alerted all producing regions of the world. In Chile, none of these bacteria have been reported in citrus species. During the years 2017 and 2019, 258 samples presenting symptoms similar to those associated with the presence of these bacteria were examined. No detection of ‘Ca. Liberibacter’ associated with “huanglongbing” disease was obtained in the tested samples; therefore, this quarantine pest is maintained as absent in Chile. However, 14 plants resulted positive for phytoplasmas enclosed in subgroups 16SrV-A (12 plants) and 16SrXIII-F (2 plants). Although they have been found in other plant species, this is the first report of these phytoplasmas in citrus worldwide.
Staphylococcus ratti sp. nov. Isolated from a Lab Rat
Authors: Kovařovic Vojtěch , Sedláček Ivo , Petráš Petr , Králová Stanislava , Mašlaňová Ivana , Švec Pavel , Neumann-Schaal Meina , Botka Tibor , Gelbíčová Tereza , Staňková Eva , Doškař Jiří , Pantůček Roman
Published: January 2022

Staphylococci from the Staphylococcus intermedius-Staphylococcus hyicus species group include numerous animal pathogens and are an important reservoir of virulence and antimicrobial resistance determinants. Due to their pathogenic potential, they are possible causative agents of zoonoses in humans; therefore, it is important to address the properties of these strains. Here we used a polyphasic taxonomic approach to characterize the coagulase-negative staphylococcal strain NRL/St 03/464T, isolated from the nostrils of a healthy laboratory rat during a microbiological screening of laboratory animals. The 16S rRNA sequence, MALDI-TOF mass spectrometry and positive urea hydrolysis and beta-glucuronidase tests clearly distinguished it from closely related Staphylococcus spp. All analyses have consistently shown that the closest relative is Staphylococcus chromogenes; however, values of digital DNA-DNA hybridization <35.3% and an average nucleotide identity <81.4% confirmed that the analyzed strain is a distinct Staphylococcus species. Whole-genome sequencing and expert annotation of the genome revealed the presence of novel variable genetic elements, including two plasmids named pSR9025A and pSR9025B, prophages, genomic islands and a composite transposon that may confer selective advantages to other bacteria and enhance their survival. Based on phenotypic, phylogenetic and genomic data obtained in this study, the strain NRL/St 03/464T (= CCM 9025T = LMG 31873T = DSM 111348T) represents a novel species with the suggested name Staphylococcus ratti sp. nov.
Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes
Authors: Santini Marija , Haberle Sara , Židovec-Lepej Snježana , Savić Vladimir , Kusulja Marija , Papić Neven , Višković Klaudija , Župetić Ivana , Savini Giovanni , Barbić Ljubo , Tabain Irena , Kutleša Marko , Krajinović Vladimir , Potočnik-Hunjadi Tanja , Dvorski Elizabeta , Butigan Tamara , Kolaric-Sviben Gordana , Stevanović Vladimir , Gorenec Lana , Grgić Ivana , Glavač Filip , Mehmedović Armin , Listeš Eddy , Vilibić-Čavlek Tatjana
Published: January 2022

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013–2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33–84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5–73), and the median hospital LOS was 34 days (range 7–97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3–5, 6 (26.0%) had slight disability/mRS 2–1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6–69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3–5, one (4.3%) had slight disability/mRS 2–1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.
Enteroviral Infections in the First Three Months of Life
Authors: Sandoni Marcello , Ciardo Lidia , Tamburini Caterina , Boncompagni Alessandra , Rossi Cecilia , Guidotti Isotta , Garetti Elisabetta , Lugli Licia , Iughetti Lorenzo , Berardi Alberto
Published: January 2022

Enteroviruses (EVs) are an important source of infection in the paediatric age, with most cases concerning the neonatal age and early infancy. Molecular epidemiology is crucial to understand the circulation of main serotypes in a specific area and period due to their extreme epidemiological variability. The diagnosis of EVs infection currently relies on the detection of EVs RNA in biological samples (usually cerebrospinal fluid and plasma, but also throat swabs and feces) through a polymerase chain reaction assay. Although EVs infections usually have a benign course, they sometimes become life threatening, especially when symptoms develop in the first few days of life. Mortality is primarily associated with myocarditis, acute hepatitis, and multi-organ failure. Neurodevelopmental sequelae have been reported following severe infections with central nervous system involvement. Unfortunately, at present, the treatment of EVs infections is mainly supportive. The use of specific antiviral agents in severe neonatal infections has been reported in single cases or studies including few neonates. Therefore, further studies are needed to confirm the efficacy of these drugs in clinical practice.
Current Understanding of the Pathogenesis of Porcine Circovirus 3
Authors: Sirisereewan Chaitawat , Thanawongnuwech Roongroje , Kedkovid Roongtham
Published: January 2022

Circoviruses are closed, circular, single-stranded DNA viruses belonging to the family Circoviridae and the genus Circovirus. To date, at least four porcine circoviruses (PCVs) have been recognized, including PCV1 to PCV4, respectively. Similar to PCV2 pathogenesis, PCV3 has been reported worldwide with myriad clinical and pathological presentations such as reproductive disorders, respiratory diseases, diarrhea etc. Current understanding of PCV3 pathogenesis is very limited since the majority of studies were mostly field observations. Interpretation of the results from such studies is not always simple. Various confounding factors affect the clinical appearance and pathological changes of the infected pigs. Recently, several experimental PCV3 infection studies have been reported, providing a better understanding of its pathogenesis. In this review, we focused on novel findings regarding PCV3 pathogenesis from both field observation and experimental infection studies. Possible factors involved in the conflicting results among the experimental infection studies are also discussed. This review article provides important insight into the current knowledge on PCV3 pathogenesis which would aid in prioritizing research in order to fill the knowledge gaps.
Rabies Vaccination in Dogs in Laos: Owner Knowledge and Serological Status of Dogs
Authors: Velander Lovisa , Fogelberg Johanna , Putthana Vannaphone , Keosengthong Amphone , Lindahl Johanna Frida
Published: January 2022

Rabies is an infectious disease which is virtually 100% fatal. Humans are most often infected through the bite of an infected dog, and most cases could be prevented by vaccinating dogs. However, vaccination coverage is insufficient in most countries where canine rabies occurs endemically. This study conducted interviews and sampling of dogs in Laos to understand more about the barriers for vaccination and to evaluate the antibody status of dogs using a commercial ELISA. The study found that only 62% out of 359 dog owners knew what rabies was, and only 24% knew the disease could be fatal. Higher education was associated with higher knowledge scores. Only 56 out of 437 (13%) dogs had been rabies vaccinated according to their owner, and out of these dogs, only 34 (61%) had antibodies, and only 48% had adequate levels (above 0.5 IU/mL). However, 24% of the dogs with no known history of vaccination had antibodies, indicating either exposure or vaccination in the past without the owner’s awareness. In conclusion, this study indicates that there is a low level of knowledge about rabies, and that owner knowledge is not a good indicator of whether a dog is vaccinated or not.
Investigation of the Potential of Heterophil/Lymphocyte Ratio as a Biomarker to Predict Colonization Resistance and Inflammatory Response to Salmonella enteritidis Infection in Chicken
Authors: Thiam Mamadou , Barreto Sánchez Astrid Lissette , Zhang Jin , Wen Jie , Zhao Guiping , Wang Qiao
Published: January 2022

Salmonella causes significant economic loss to the poultry industry and represents a real threat to human health. The region of difference 21 (ROD21) pathogenicity island removal is a genetic mechanism by which Salmonellaenteritidis (SE) invades the intestinal epithelium and induces systemic infection in mice. The heterophil/lymphocyte (H/L) ratio reflects the chicken’s robustness and immune system status. The H/L ratio is considered a disease resistance trait, and it could be used as a marker for selecting Salmonella resistance in live chickens. However, the association of the H/L ratio with Salmonella resistance and the inflammatory response remains to be elucidated. Moreover, the kinetics of ROD21 excision in the intestine and immune organs of chickens is unknown. Therefore, this study aimed to investigate the bacterial load, the ROD21 excision, the IL-1β, IL-8, and INF-γ blood serum concentration kinetics, and the association with the H/L ratio in chicken at 1, 3, 7, and 21 days post-SE infection. The results showed a significant correlation between the H/L ratio and the bacterial load in the ileum and caecum at 7 dpi. The ROD21 pathogenicity island absolute and relative excision in the caecum were positively correlated at 1 dpi but negatively correlated at 7 dpi with the H/L ratio. However, in the liver, we found the opposite tendency. The association of the H/L ratio with IL-1β, IL-8, and INF-γ blood serum concentrations showed that a low H/L ratio is correlated with increased IL-1β and INF-γ at 21 dpi. This study confirmed that the H/L ratio is associated with robustness and Salmonella-resistance in chicken. The methodology used in this study can separate individuals into susceptible and resistant and can help in the selection and breeding of Salmonella-resistant chickens.
Odontogenic Cervicofacial Necrotizing Fasciitis: Microbiological Characterization and Management of Four Clinical Cases
Authors: Böttger Sebastian , Zechel-Gran Silke , Schmermund Daniel , Streckbein Philipp , Wilbrand Jan-Falco , Knitschke Michael , Pons-Kühnemann Jörn , Hain Torsten , Weigel Markus , Imirzalioglu Can , Howaldt Hans-Peter , Domann Eugen , Attia Sameh
Published: January 2022

Necrotizing fasciitis of the head and neck is a rare, very severe disease, which, in most cases, originates from odontogenic infections and frequently ends with the death of the patient. Rapid surgical intervention in combination with a preferably pathogen-specific antibiotic therapy can ensure patients’ survival. The question arises concerning which pathogens are causative for the necrotizing course of odontogenic inflammations. Experimental 16S-rRNA gene analysis with next-generation sequencing and bioinformatics was used to identify the microbiome of patients treated with an odontogenic necrotizing infection and compared to the result of the routine culture. Three of four patients survived the severe infection, and one patient died due to septic multiorgan failure. Microbiome determination revealed findings comparable to typical odontogenic abscesses. A specific pathogen which could be causative for the necrotizing course could not be identified. Early diagnosis and rapid surgical intervention and a preferably pathogen-specific antibiotic therapy, also covering the anaerobic spectrum of odontogenic infections, are the treatments of choice. The 16S-rRNA gene analysis detected significantly more bacteria than conventional methods; therefore, molecular methods should become a part of routine diagnostics in medical microbiology.
Porcine Deltacoronaviruses: Origin, Evolution, Cross-Species Transmission and Zoonotic Potential
Authors: Kong Fanzhi , Wang Qiuhong , Kenney Scott P. , Jung Kwonil , Vlasova Anastasia N. , Saif Linda J.
Published: January 2022

Porcine deltacoronavirus (PDCoV) is an emerging enteropathogenic coronavirus of swine that causes acute diarrhoea, vomiting, dehydration and mortality in seronegative neonatal piglets. PDCoV was first reported in Hong Kong in 2012 and its etiological features were first characterized in the United States in 2014. Currently, PDCoV is a concern due to its broad host range, including humans. Chickens, turkey poults, and gnotobiotic calves can be experimentally infected by PDCoV. Therefore, as discussed in this review, a comprehensive understanding of the origin, evolution, cross-species transmission and zoonotic potential of epidemic PDCoV strains is urgently needed.
Chitosan/Sodium Dodecyl Sulfate Complexes for Microencapsulation of Vitamin E and Its Release Profile—Understanding the Effect of Anionic Surfactant
Authors: Milinković Budinčić Jelena , Petrović Lidija , Đekić Ljiljana , Aleksić Milijana , Fraj Jadranka , Popović Senka , Bučko Sandra , Katona Jaroslav , Spasojević Ljiljana , Škrbić Jelena , Malenović Anđelija
Published: January 2022

Microencapsulation of bioactive substances is a common strategy for their protection and release rate control. The use of chitosan (Ch) is particularly promising due to its abundance, biocompatibility, and interaction with anionic surfactants to form complexes of different characteristics with relevance for use in microcapsule wall design. In this study, Ch/sodium dodecyl sulfate (SDS) microcapsules, without and with cross-linking agent (formaldehyde (FA) or glutaraldehyde (GA)), were obtained by the spray drying of vitamin E loaded oil-in-water emulsion. All of the microcapsules had good stability during the drying process. Depending on the composition, their product yield, moisture content, and encapsulation efficiency varied between 11–34%, 1.14–1.62%, and 94–126%, respectively. SEM and FTIR analysis results indicate that SDS as well as cross-linkers significantly affected the microcapsule wall properties. The profiles of in vitro vitamin E release from the investigated microcapsules fit with the Korsmeyer-Peppas model (r2 > 0.9). The chemical structure of the anionic surfactant was found to have a significant effect on the vitamin E release mechanism. Ch/SDS coacervates may build a microcapsule wall without toxic crosslinkers. This enabled the combined diffusion/swelling based release mechanism of the encapsulated lipophilic substance, which can be considered favorable for utilization in food and pharmaceutical products.
FDA-Approved Oximes and Their Significance in Medicinal Chemistry
Authors: Dhuguru Jyothi , Zviagin Eugene , Skouta Rachid
Published: January 2022

Despite the scientific advancements, organophosphate (OP) poisoning continues to be a major threat to humans, accounting for nearly one million poisoning cases every year leading to at least 20,000 deaths worldwide. Oximes represent the most important class in medicinal chemistry, renowned for their widespread applications as OP antidotes, drugs and intermediates for the synthesis of several pharmacological derivatives. Common oxime based reactivators or nerve antidotes include pralidoxime, obidoxime, HI-6, trimedoxime and methoxime, among which pralidoxime is the only FDA-approved drug. Cephalosporins are β-lactam based antibiotics and serve as widely acclaimed tools in fighting bacterial infections. Oxime based cephalosporins have emerged as an important class of drugs with improved efficacy and a broad spectrum of anti-microbial activity against Gram-positive and Gram-negative pathogens. Among the several oxime based derivatives, cefuroxime, ceftizoxime, cefpodoxime and cefmenoxime are the FDA approved oxime-based antibiotics. Given the pharmacological significance of oximes, in the present paper, we put together all the FDA-approved oximes and discuss their mechanism of action, pharmacokinetics and synthesis.
Development of 3D-Printed, Liquisolid and Directly Compressed Glimepiride Tablets, Loaded with Black Seed Oil Self-Nanoemulsifying Drug Delivery System: In Vitro and In Vivo Characterization
Authors: Ahmed Tarek A. , Alotaibi Hanadi A. , Alharbi Waleed S. , Safo Martin K. , El-Say Khalid M.
Published: January 2022

Glimepiride is characterized by an inconsistent dissolution and absorption profile due to its limited aqueous solubility. The aim of this study was to develop glimepiride tablets using three different manufacturing techniques, as well as to study their quality attributes and pharmacokinetics behavior. Black seed oil based self-nanoemulsifying drug delivery system (SNEDDS) formulation was developed and characterized. Glimepiride liquisolid and directly compressed tablets were prepared and their pre-compression and post-compression characteristics were evaluated. Semi-solid pastes loaded with SNEDDS were prepared and used to develop three-dimensional printing tablets utilizing the extrusion technique. In vivo comparative pharmacokinetics study was conducted on Male Wistar rats using a single dose one-period parallel design. The developed SNEDDS formulation showed a particle size of 45.607 ± 4.404 nm, and a glimepiride solubility of 25.002 ± 0.273 mg/mL. All the studied tablet formulations showed acceptable pre-compression and post-compression characteristics and a difference in their in vitro drug release behavior. The surface of the liquisolid and directly compressed tablets was smooth and non-porous, while the three-dimensional printing tablets showed a few porous surfaces. The inner structure of the liquisolid tablets showed some cracks and voids between the incorporated tablet ingredients while that of the three-dimensional printing tablets displayed some tortuosity and a gel porous-like structure. Most of the computed pharmacokinetic parameters improved with the liquisolid and three-dimensional printed tablets. The relative bioavailabilities of the three-dimensional printed and liquisolid tablets compared to commercial product were 121.68% and 113.86%, respectively. Therefore, the liquisolid and three-dimensional printed tablets are promising techniques for modifying glimepiride release and improving in vivo performance but more clinical investigations are required.
Fabrication and Evaluation of Quercetin Nanoemulsion: A Delivery System with Improved Bioavailability and Therapeutic Efficacy in Diabetes Mellitus
Authors: Mahadev Manohar , Nandini Hittanahalli S. , Ramu Ramith , Gowda Devegowda V. , Almarhoon Zainab M. , Al-Ghorbani Mohammed , Mabkhot Yahia N.
Published: January 2022

The current study was intended to fabricate and evaluate ultrasonically assisted quercetin nanoemulsion (Que-NE) for improved bioavailability and therapeutic effectiveness against diabetes mellitus in rats. Ethyl oleate, Tween 20, and Labrasol were chosen as oil, surfactant, and cosurfactant, respectively. Box–Behnken design (BBD) was employed to study the influence of process variables such as % surfactant and cosurfactant mixture (Smix) (5 to 7%), % amplitude (20–30%) and sonication time (2.5–7.5 min) on droplet size, polydispersibility index (PDI), and % entrapment efficiency (%EE) were studied. The optimization predicted that 9% Smix at 25% amplitude for 2.5 min would produce Que-NE with a droplet size of 125.51 nm, 0.215 PDI, and 87.04% EE. Moreover, the optimized Que-NE exhibited appreciable droplet size and PDI when stored at 5, 30, and 40 °C for 45 days. Also, the morphological characterization by transmission electron microscope (TEM) indicated the spherical shape of the optimized nanoemulsion. Furthermore, the Que-NE compared to pure quercetin exhibited superior release and enhanced oral bioavailability. The streptozocin-induced antidiabetic study in rats revealed that the Que-NE had remarkable protective and therapeutic properties in managing body weight, blood glucose level, lipid profile, and tissue injury markers, alongside the structure of pancreatic β-cells and hepatocytes being protected. Thus, the developed Que-NE could be of potential use as a substitute strategy for diabetes.
Relevance of Circulating Tumor Cells as Predictive Markers for Cancer Incidence and Relapse
Authors: Chelakkot Chaithanya , Yang Hobin , Shin Young Kee
Published: January 2022

Shedding of cancer cells from the primary site or undetectable bone marrow region into the circulatory system, resulting in clinically overt metastasis or dissemination, is the hallmark of unfavorable invasive cancers. The shed cells remain in circulation until they extravasate to form a secondary metastatic lesion or undergo anoikis. The circulating tumor cells (CTCs) found as single cells or clusters carry a plethora of information, are acknowledged as potential biomarkers for predicting cancer prognosis and cancer progression, and are supposed to play key roles in determining tailored therapies for advanced diseases. With the advent of novel technologies that allow the precise isolation of CTCs, more and more clinical trials are focusing on the prognostic and predictive potential of CTCs. In this review, we summarize the role of CTCs as a predictive marker for cancer incidence, relapse, and response to therapy.
Packaging and Delivery of Asthma Therapeutics
Authors: Mathis Bryan J. , Kusumoto Misa , Zaboronok Alexander , Hiramatsu Yuji
Published: January 2022

Asthma is a life-altering, chronic disease of heterogenous origin that features a complex interplay of immune and environmental signaling. Although very little progress has been made in prevention, diverse types of medications and delivery systems, including nanoscale systems, have been or are currently being developed to control airway inflammation and prevent exacerbations and fibrosis. These medications are delivered through mechanical methods, with various inhalers (with benefits and drawbacks) existing, and new types offering some variety in delivery. Of particular interest is the progress being made in nanosized materials for efficient penetration into the epithelial mucus layer and delivery into the deepest parts of the lungs. Liposomes, nanoparticles, and extracellular vesicles, both natural and synthetic, have been explored in animal models of asthma and have produced promising results. This review will summarize and synthesize the latest developments in both macro-(inhaler) and micro-sized delivery systems for the purpose of treating asthma patients.
Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur®) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency
Authors: Sinegubova Maria , Vorobiev Ivan , Klishin Anatoly , Eremin Dmitry , Orlova Nadezhda , Orlova Natalya , Polzikov Mikhail
Published: January 2022

Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity.
Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2
Authors: Gagliardi Maria , Ashizawa Ana Tari
Published: January 2022

The B-cell lymphoma 2 (Bcl-2) family, comprised of pro- and anti-apoptotic proteins, regulates the delicate balance between programmed cell death and cell survival. The Bcl-2 family is essential in the maintenance of tissue homeostasis, but also a key culprit in tumorigenesis. Anti-apoptotic Bcl-2, the founding member of this family, was discovered due to its dysregulated expression in non-Hodgkin’s lymphoma. Bcl-2 is a central protagonist in a wide range of human cancers, promoting cell survival, angiogenesis and chemotherapy resistance; this has prompted the development of Bcl-2-targeting drugs. Antisense oligonucleotides (ASO) are highly specific nucleic acid polymers used to modulate target gene expression. Over the past 25 years several Bcl-2 ASO have been developed in preclinical studies and explored in clinical trials. This review will describe the history and development of Bcl-2-targeted ASO; from initial attempts, optimizations, clinical trials undertaken and the promising candidates at hand.
Manganese in Diagnostics: A Preformulatory Study
Authors: Sguizzato Maddalena , Pula Walter , Bordin Anna , Pagnoni Antonella , Drechsler Markus , Marvelli Lorenza , Cortesi Rita
Published: January 2022

This investigation aims to find lipid-based nanosystems to be used as tools to deliver manganese for diagnostic purposes in multimodal imaging techniques. In particular, the study describes the production and characterization of aqueous dispersions of anionic liposomes as delivery systems for two model manganese-based compounds, namely manganese chloride and manganese acetylacetonate. Negatively charged liposomes were obtained using four different anionic surfactants, namely sodium docusate (SD), N-lauroylsarcosine (NLS), Protelan AG8 (PAG) and sodium lauroyl lactylate (SLL). Liposomes were produced by the direct hydration method followed by extrusion and characterized in terms of size, polydispersity, surface charge and stability over time. After extrusion, liposomes are homogeneous and monodispersed with an average diameter not exceeding 200 nm and a negative surface charge as confirmed by ζ potential measurement. Moreover, as indicated by atomic absorption spectroscopy analyses, the loading of manganese-based compounds was almost quantitative. Liposomes containing NLS or SLL were the most stable over time and the presence of manganese-based compounds did not affect their size distribution. Liposomes containing PAG and SD were instable and therefore discarded. The in vitro cytotoxicity of the selected anionic liposomes was evaluated by MTT assay on human keratinocyte. The obtained results highlighted that the toxicity of the formulations is dose dependent.
Tailoring of Novel Azithromycin-Loaded Zinc Oxide Nanoparticles for Wound Healing
Authors: Saddik Mohammed S. , Elsayed Mahmoud M. A. , El-Mokhtar Mohamed A. , Sedky Haitham , Abdel-Aleem Jelan A. , Abu-Dief Ahmed M. , Al-Hakkani Mostafa F. , Hussein Hazem L. , Al-Shelkamy Samah A. , Meligy Fatma Y. , Khames Ali , Abou-Taleb Heba A.
Published: January 2022

Skin is the largest mechanical barrier against invading pathogens. Following skin injury, the healing process immediately starts to regenerate the damaged tissues and to avoid complications that usually include colonization by pathogenic bacteria, leading to fever and sepsis, which further impairs and complicates the healing process. So, there is an urgent need to develop a novel pharmaceutical material that promotes the healing of infected wounds. The present work aimed to prepare and evaluate the efficacy of novel azithromycin-loaded zinc oxide nanoparticles (AZM-ZnONPs) in the treatment of infected wounds. The Box–Behnken design and response surface methodology were used to evaluate loading efficiency and release characteristics of the prepared NPs. The minimum inhibitory concentration (MIC) of the formulations was determined against Staphylococcus aureus and Escherichia coli. Moreover, the anti-bacterial and wound-healing activities of the AZM-loaded ZnONPs impregnated into hydroxyl propyl methylcellulose (HPMC) gel were evaluated in an excisional wound model in rats. The prepared ZnONPs were loaded with AZM by adsorption. The prepared ZnONPs were fully characterized by XRD, EDAX, SEM, TEM, and FT-IR analysis. Particle size distribution for the prepared ZnO and AZM-ZnONPs were determined and found to be 34 and 39 nm, respectively. The mechanism by which AZM adsorbed on the surface of ZnONPs was the best fit by the Freundlich model with a maximum load capacity of 160.4 mg/g. Anti-microbial studies showed that AZM-ZnONPs were more effective than other controls. Using an experimental infection model in rats, AZM-ZnONPs impregnated into HPMC gel enhanced bacterial clearance and epidermal regeneration, and stimulated tissue formation. In conclusion, AZM -loaded ZnONPs are a promising platform for effective and rapid healing of infected wounds.
Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family
Authors: Merlani Maia , Scheibel Dieter M. , Barbakadze Vakhtang , Gogilashvili Lali , Amiranashvili Lela , Geronikaki Athina , Catania Valentina , Schillaci Domenico , Gallo Giuseppe , Gitsov Ivan
Published: January 2022

This study reports the first enzymatic synthesis leading to several oligomer analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, extracted from plants of the Boraginaceae family has shown a wide spectrum of pharmacological properties, including antimicrobial activity. Enzymatic ring opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (MDBPO) using lipase from Candida rugosa leads to formation of poly[2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane] (PMDBPO), with a degree of polymerization up to 5. Catalytic debenzylation of PMDBPO using H2 on Pd/C yields poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) without loss in molecular mass. Antibacterial assessment of natural polyethers from different species of Boraginaceae family Symhytum asperum, S. caucasicum,S. grandiflorum, Anchusa italica, Cynoglossum officinale, and synthetic polymers, poly[2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (PMDMPO) and PMDHPO, reveals that only the synthetic analogue produced in this study (PMDHPO) exhibits a promising antimicrobial activity against pathogenic strains S.aureus ATCC 25923 and E.coli ATCC 25922 the minimum inhibitory concentration (MIC) being 100 µg/mL.
SCMTHP: A New Approach for Identifying and Characterizing of Tumor-Homing Peptides Using Estimated Propensity Scores of Amino Acids
Authors: Charoenkwan Phasit , Chiangjong Wararat , Nantasenamat Chanin , Moni Mohammad Ali , Lio’ Pietro , Manavalan Balachandran , Shoombuatong Watshara
Published: January 2022

Tumor-homing peptides (THPs) are small peptides that can recognize and bind cancer cells specifically. To gain a better understanding of THPs’ functional mechanisms, the accurate identification and characterization of THPs is required. Although some computational methods for in silico THP identification have been proposed, a major drawback is their lack of model interpretability. In this study, we propose a new, simple and easily interpretable computational approach (called SCMTHP) for identifying and analyzing tumor-homing activities of peptides via the use of a scoring card method (SCM). To improve the predictability and interpretability of our predictor, we generated propensity scores of 20 amino acids as THPs. Finally, informative physicochemical properties were used for providing insights on characteristics giving rise to the bioactivity of THPs via the use of SCMTHP-derived propensity scores. Benchmarking experiments from independent test indicated that SCMTHP could achieve comparable performance to state-of-the-art method with accuracies of 0.827 and 0.798, respectively, when evaluated on two benchmark datasets consisting of Main and Small datasets. Furthermore, SCMTHP was found to outperform several well-known machine learning-based classifiers (e.g., decision tree, k-nearest neighbor, multi-layer perceptron, naive Bayes and partial least squares regression) as indicated by both 10-fold cross-validation and independent tests. Finally, the SCMTHP web server was established and made freely available online. SCMTHP is expected to be a useful tool for rapid and accurate identification of THPs and for providing better understanding on THP biophysical and biochemical properties.
Boswellia sacra Extract-Loaded Mesoporous Bioactive Glass Nano Particles: Synthesis and Biological Effects
Authors: Ilyas Kanwal , Singer Lamia , Akhtar Muhammad , Bourauel Christoph , Boccaccini Aldo
Published: January 2022

Bioactive glasses (BGs) are being increasingly considered for numerous biomedical applications. The loading of natural compounds onto BGs to increase the BG biological activity is receiving increasing attention. However, achieving efficient loading of phytotherapeutic compounds onto the surface of bioactive glass is challenging. The present work aimed to prepare novel amino-functionalized mesoporous bioactive glass nanoparticles (MBGNs) loaded with the phytotherapeutic agent Boswellia sacra extract. The prepared amino-functionalized MBGNs showed suitable loading capacity and releasing time. MBGNs (nominal composition: 58 wt% SiO2, 37 wt% CaO, 5 wt% P2O5) were prepared by sol-gel-modified co-precipitation method and were successfully surface-modified by using 3-aminopropyltriethoxysilane (APTES). In order to evaluate MBGNs loaded with Boswellia sacra, morphological analysis, biological studies, physico-chemical and release studies were performed. The successful functionalization and loading of the natural compound were confirmed with FTIR, zeta-potential measurements and UV-Vis spectroscopy, respectively. Structural and morphological evaluation of MBGNs was done by XRD, SEM and BET analyses, whereas the chemical analysis of the plant extract was done using GC/MS technique. The functionalized MBGNs showed high loading capacity as compared to non-functionalized MBGNs. The release studies revealed that Boswellia sacra molecules were released via controlled diffusion and led to antibacterial effects against S. aureus (Gram-positive) bacteria. Results of cell culture studies using human osteoblastic-like cells (MG-63) indicated better cell viability of the Boswellia sacra-loaded MBGNs as compared to the unloaded MBGNs. Therefore, the strategy of combining the properties of MBGNs with the therapeutic effects of Boswellia sacra represents a novel, convenient step towards the development of phytotherapeutic-loaded antibacterial, inorganic materials to improve tissue healing and regeneration.