bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperbranched Poly(β-amino ester)s (HPAEs) Structure Optimisation for Enhanced Gene Delivery: Non-Ideal Termination Elimination
Authors: Li Yinghao , He Zhonglei , Lyu Jing , Wang Xianqing , Qiu Bei , Lara-Sáez Irene , Zhang Jing , Zeng Ming , Xu Qian , A Sigen , Curtin James F. , Wang Wenxin
Published: November 2022

Many polymeric gene delivery nano-vectors with hyperbranched structures have been demonstrated to be superior to their linear counterparts. The higher delivery efficacy is commonly attributed to the abundant terminal groups of branched polymers, which play critical roles in cargo entrapment, material-cell interaction, and endosome escape. Hyperbranched poly(β-amino ester)s (HPAEs) have developed as a class of safe and efficient gene delivery vectors. Although numerous research has been conducted to optimise the HPAE structure for gene delivery, the effect of the secondary amine residue on its backbone monomer, which is considered the non-ideal termination, has never been optimised. In this work, the effect of the non-ideal termination was carefully evaluated. Moreover, a series of HPAEs with only ideal terminations were synthesised by adjusting the backbone synthesis strategy to further explore the merits of hyperbranched structures. The HPAE obtained from modified synthesis methods exhibited more than twice the amounts of the ideal terminal groups compared to the conventional ones, determined by NMR. Their transfection performance enhanced significantly, where the optimal HPAE candidates developed in this study outperformed leading commercial benchmarks for DNA delivery, including Lipofectamine 3000, jetPEI, and jetOPTIMUS.
A Comprehensive Review on Nutraceuticals: Therapy Support and Formulation Challenges
Authors: Puri Vivek , Nagpal Manju , Singh Inderbir , Singh Manjinder , Dhingra Gitika Arora , Huanbutta Kampanart , Dheer Divya , Sharma Ameya , Sangnim Tanikan
Published: November 2022

Nutraceuticals are the nourishing components (hybrid of nutrition and pharmaceuticals) that are biologically active and possess capability for maintaining optimal health and benefits. These products play a significant role in human health care and its endurance, most importantly for the future therapeutic development. Nutraceuticals have received recognition due to their nutritional benefits along with therapeutic effects and safety profile. Nutraceuticals are globally growing in the field of services such as health care promotion, disease reduction, etc. Various drug nutraceutical interactions have also been elaborated with various examples in this review. Several patents on nutraceuticals in agricultural applications and in various diseases have been stated in the last section of review, which confirms the exponential growth of nutraceuticals’ market value. Nutraceuticals have been used not only for nutrition but also as a support therapy for the prevention and treatment of various diseases, such as to reduce side effects of cancer chemotherapy and radiotherapy. Diverse novel nanoformulation approaches tend to overcome challenges involved in formulation development of nutraceuticals. Prior information on various interactions with drugs may help in preventing any deleterious effects of nutraceuticals products. Nanotechnology also leads to the generation of micronized dietary products and other nutraceutical supplements with improved health benefits. In this review article, the latest key findings (clinical studies) on nutraceuticals that show the therapeutic action of nutraceutical’s bioactive molecules on various diseases have also been discussed.
Positive Additive and Multiplicative Interactions among Clustered Components of Metabolic Syndrome with Type 2 Diabetes Mellitus among Brazilian Adolescent Students
Authors: Deusdará Rodolfo , de Moura Souza Amanda , Szklo Moyses
Published: November 2022

Background: It is still controversial whether the joint effect of Metabolic syndrome (MetS) components is greater than that expected based on their independent effects, regarding type 2 diabetes mellitus in adolescents. We evaluated additive and multiplicative interactions between pair-wise combinations of metabolic syndrome components regarding type 2 diabetes mellitus. Methods: We studied 37,815 Brazilian adolescents from a national school-based survey, The Study of Cardiovascular Risk Factors in Adolescents (Portuguese acronym, ERICA). A Poisson regression model was used to calculate sex-, age-, obesity-, smoking status-, sedentary behavior-, physical inactivity-, alcoholic consumption- and socioeconomic status-adjusted prevalence ratios to evaluate both additive and multiplicative interactions. Results: In the comparison of observed and expected joint effects, relative excess risk due to additive interaction (RERI) for high triglycerides and low high-density lipoprotein-cholesterol, high triglycerides and elevated waist circumference, elevated waist circumference and low high-density lipoprotein-cholesterol and elevated waist circumference and high blood pressure were 2.53 (−0.41, 5.46), 2.86 (−2.89, 8.61), 1.71 (−1.05, 4.46) and 0.97 (0.15, 1.79), respectively, thus suggesting additive interactions. Multiplicative interactions for those pairs of components were also observed, as expressed by interaction ratios > 1.0. Conclusions: The joint presence of some of the components of MetS showed a greater association with the prevalence of type 2 diabetes mellitus in adolescents than expected from the sum of their isolated effects. From a public health perspective, preventing one of the components of the pairs that interact may result in a greater reduction in the prevalence of T2DM than focusing on an individual component that does not interact with another component.
Anti-Inflammatory Effect of Korean Propolis on Helicobacter pylori-Infected Gastric Mucosal Injury Mice Model
Authors: Song Moon-Young , Lee Da-Young , Han Young-Min , Kim Eun-Hee
Published: November 2022

Propolis, a natural resinous substance obtained from a variety of buds and plants, has been reported to possess various biological functions. Several recent studies have demonstrated the inhibitory effects of propolis on the growth of Helicobacter pylori (H. pylori) in vitro; however, current research efforts on Korean propolis (KP) remain insufficient especially in vivo. Our study aims to investigate the anti-inflammatory effect and molecular mechanism of KP on mouse gastric mucosa during H. pylori infection. We examined an in vivo H. pylori-induced gastric mucosal injury mice model. We found that KP inhibited the growth of H. pylori and attenuated the expression of H. pylori virulence factors such as cytotoxin-associated gene A, encoding urease A subunit, surface antigen gene and neutrophil-activating protein A. Moreover, KP reduced both gross lesions and pathological scores in H. pylori-challenged mice. In addition, KP markedly restrained the production of pro-inflammatory cytokines and nitric oxide levels compared with an untreated H. pylori-infected group. In particular, we found that KP repressed the phosphorylation of IκBα and NF-κB p65 subunit, and subsequently suppressed their downstream target genes. Taken together, these findings demonstrate the beneficial effects of KP on inflammation through the inhibition of NF-κB signaling as well as inhibition of H. pylori growth in a mouse model infected with H. pylori. This suggests the potential application of KP as a natural supplement for patient’s suffering from gastric mucosal injury caused by H. pylori infection.
Effects of Irvingia gabonensis Extract on Metabolism, Antioxidants, Adipocytokines, Telomere Length, and Aerobic Capacity in Overweight/Obese Individuals
Authors: Nonsa-ard Rujira , Aneknan Ploypailin , Tong-un Terdthai , Honsawek Sittisak , Leelayuwat Naruemon
Published: November 2022

We investigated the effects of Irvingia gabonensis (IG) kernel extract on the metabolism, adiposity indices, redox status, inflammation, adipocytokines, blood leukocyte relative telomere length (RTL), and aerobic capacity of overweight/obese individuals. All participants used the first 12-week phase to monitor body weight. They were then randomly divided into two groups: (1) 300 mg IG or (2) placebo (PLA). Both groups took one tablet per day for 12 weeks. The variables were measured before supplementation and after 3, 6, and 12 weeks of supplementation. RTL and aerobic capacity were measured before and after 12 weeks. Compared with the PLA, the IG increased plasma vitamin C after supplementation at 6 (p < 0.01) and 12 weeks (p < 0.05) and serum adiponectin after 3 weeks (p < 0.05). Compared with before supplementation, plasma malondialdehyde in the IG and serum leptin in the PLA were decreased after 12-week supplementation, without any differences between the groups. There were no differences between groups with respect to metabolism, inflammation, RTL, and aerobic capacity after the supplementation. We suggest that 12-week daily IG supplementation improved plasma vitamin C and adiponectin. The findings show the possible mechanism contributing to the effect of IG supplementation on a reduction in obesity-related complications.
α-Bisabolol Attenuates NF-κB/MAPK Signaling Activation and ER-Stress-Mediated Apoptosis by Invoking Nrf2-Mediated Antioxidant Defense Systems against Doxorubicin-Induced Testicular Toxicity in Rats
Authors: Arunachalam Seenipandi , Nagoor Meeran Mohamed Fizur , Azimullah Sheikh , Kumar Jha Niraj , Saraswathiamma Dhanya , Albawardi Alia , Beiram Rami , Ojha Shreesh
Published: November 2022

The present study investigated the effects of α-bisabolol on DOX-induced testicular damage in rats. Testicular damage was induced in rats by injecting DOX (12.5 mg/kg, i.p., single dose) into rats. α-Bisabolol (25 mg/kg, i.p.) was administered to the rats along with DOX pre- and co-treatment daily for a period of 5 days. DOX-injected rats showed a decrease in absolute testicular weight and relative testicular weight ratio along with concomitant changes in the levels/expression levels of oxidative stress markers and Nrf2 expression levels in the testis. DOX injection also triggered the activation of NF-κB/MAPK signaling and increased levels/expression levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and inflammatory mediators (iNOS and COX-2) in the testis. DOX triggered apoptosis, manifested by an increment in the expression levels of pro-apoptotic markers (Bax, Bcl2, cleaved caspase-3 and -9, and cytochrome-C) and a decline in the expression levels of anti-apoptotic markers (Bcl-xL and Bcl2) in the testis. Additionally, light microscopy revealed the changes in testicular architecture. α-Bisabolol rescued alterations in the testicular weight; restored all biochemical markers; modulated the expression levels of Nrf2-mediated antioxidant responses, NF-κB/MAPK signaling, endoplasmic reticulum (ER) stress, and apoptosis markers in DOX-injected testicular toxicity in rats. Based on our findings, it can be concluded that α-bisabolol has the potential to attenuate DOX-induced testicular injury by modifying NF-κB/MAPK signaling and the ER-stress-mediated mitochondrial pathway of apoptosis by invoking Nrf2-dependent antioxidant defense systems in rats. Based on the findings of the present study, α-bisabolol could be suggested for use as an agent or adjuvant with chemotherapeutic drugs to attenuate their deleterious effects of DOX on many organs including the testis. However, further regulatory toxicology and preclinical studies are necessary before making recommendations in clinical tests.
The Relative Merits of Observational and Experimental Research: Four Key Principles for Optimising Observational Research Designs
Authors: Hamlin Robert
Published: November 2022

The main barrier to the publication of observational research is a perceived inferiority to randomised designs with regard to the reliability of their conclusions. This commentary addresses this issue and makes a set of recommendations. It analyses the issue of research reliability in detail and fully describes the three sources of research unreliability (certainty, risk and uncertainty). Two of these (certainty and uncertainty) are not adequately addressed in most research texts. It establishes that randomised designs are vulnerable as observation studies to these two sources of unreliability, and are therefore not automatically superior to observational research in all research situations. Two key principles for reducing research unreliability are taken from R.A. Fisher’s early work on agricultural research. These principles and their application are described in detail. The principles are then developed into four key principles that observational researchers should follow when they are designing observational research exercises in nutrition. It notes that there is an optimal sample size for any particular research exercise that should not be exceeded. It concludes that best practice in observational research is to replicate this optimal sized observational exercise multiple times in order to establish reliability and credibility.
The Role of Intermittent Fasting in the Management of Nonalcoholic Fatty Liver Disease: A Narrative Review
Authors: Lavallee Celeste M. , Bruno Andreina , Ma Christopher , Raman Maitreyi
Published: November 2022

Intermittent fasting is a non-pharmacological dietary approach to management of obesity and metabolic syndrome, involving periodic intervals of complete or near-complete abstinence from food and energy-containing fluids. This dietary strategy has recently gained significant popularity in mainstream culture and has been shown to induce weight loss in humans, reduce gut and systemic inflammation, and improve gut microbial diversity and dysbiosis (largely in animal models). It has been hypothesized that intermittent fasting could be beneficial in the management of nonalcoholic fatty liver disease, given the condition’s association with obesity. This review summarizes protocols, potential mechanisms of action, and evidence for intermittent fasting in nonalcoholic fatty liver disease. It also highlights practical considerations for implementing intermittent fasting in clinical practice. A search of the literature for English-language articles related to intermittent fasting or time-restricted feeding and liver disease was completed in PubMed and Google Scholar. Potential mechanisms of action for effects of intermittent fasting included modulation of circadian rhythm, adipose tissue and adipokines, gut microbiome, and autophagy. Preclinical, epidemiological, and clinical trial data suggested clinical benefits of intermittent fasting on metabolic and inflammatory markers in humans. However, there was a paucity of evidence of its effects in patients with nonalcoholic fatty liver disease. More clinical studies are needed to determine mechanisms of action and to evaluate safety and efficacy of intermittent fasting in this population.
The Role of Kiwifruit in Supporting Psychological Well-Being: A Rapid Review of the Literature
Authors: Billows Michael , Kakoschke Naomi , Zajac Ian T.
Published: November 2022

Consumption of vitamin-rich fruits and vegetables is emerging as a recommendation for the prevention and treatment of depression and anxiety. This review sought to examine literature investigating the role of kiwifruit in supporting psychological well-being in adult populations through increased vitamin C intake. The literature search using CINAHL, Embase and PubMed databases was restricted to English-language articles published from 2005 through July 2022. Inclusion criteria were randomized trials that delivered kiwifruit interventions to adult populations assessing psychological well-being. Studies were assessed for bias using the Joanna Briggs Institute critical appraisal tool for randomized controlled trials. The literature search identified two eligible trials involving 202 participants that delivered gold kiwifruit interventions and evaluated aspects of psychological well-being (e.g., mood disturbance, vitality, vigour, depression). Daily consumption of two gold kiwifruit was associated with significant reductions in mood disturbance and fatigue, and significant increases in well-being and vigour. Larger effects were observed in participants with higher baseline mood disturbance. Additional research involving a broader range of cohorts and isolating the effects of other micronutrients within gold kiwifruit implicated in the pathophysiology of depression is warranted. Overall, preliminary evidence suggests that daily consumption of two gold kiwifruit might improve psychological well-being in adult populations.
Effect of a Multi-Strain Probiotic on Growth and Time to Reach Full Feeds in Preterm Neonates
Authors: Sowden Marwyn , van Niekerk Evette , Bulabula Andre Nyandwe Hamama , Twisk Jos , van Weissenbruch Mirjam Maria
Published: November 2022

Background: The main nutritional goal for premature neonates is to achieve a postnatal growth rate that the neonate would have experienced in utero. Postnatal growth failure is, however, very common in very and extremely low birth weight neonates. The use of probiotics shows promising results in reducing the time for full feeds, as well as in increased weight gain. The optimal probiotic strain has, however, not been elucidated. The aim of the present study was to evaluate the difference in the growth and time to reach full feeds between the two treatment arms, using LabinicTM as a multi-strain probiotic and a placebo. Methods: We conducted a double-blind, placebo-controlled, randomized clinical trial investigating the effect of a multi strain probiotic (LabinicTM) on various outcomes in preterm neonates. The results on the time to reach full feeds and the growth will be discussed in this paper. A probiotic or placebo was given once daily to the neonates for 28 days. Weight and feeding volume were measured daily, and length and head circumference were measured weekly. Results: The probiotic group reached full feeds earlier 8.7 days; ± 2.0 than the placebo group 9.7 days; ±4.3 (p = 0.04) and regained their birthweight earlier than the placebo group 11.5 days ± 6.3 vs. 13.3 days ± 6.3 (p = 0.06). From day 21 onwards, the probiotic group showed a significantly greater crude gain in weight (p < 0.001) than the placebo group (estimated difference between the two groups day 21: 56.7 g and at day 28: 83.7 g. There was a significant improvement observed in the weight Z-score change in the probiotic group over the 28-day period. Conclusion: The use of a multi-strain probiotic (LabinicTM) shows great potential as a low-cost, low-risk intervention in reducing the time to reach full feeds as well as shortening the time to regain birthweight. The probiotic had an additional beneficial impact on Z-score change in weight potentially decreasing post-natal growth restriction.
Antioxidant Capacity and Protective Effect of Cow Placenta Extract on D-Galactose-Induced Skin Aging in Mice
Authors: Shen Liu-Hong , Fan Lei , Zhang Yue , Shen Yu , Su Zhe-Tong , Peng Guang-Neng , Deng Jun-Liang , Zhong Zhi-Jun , Wu Xiao-Feng , Yu Shu-Min , Cao Sui-Zhong , Zong Xiao-Lan
Published: November 2022

Placental extract has been used for skin care and delaying skin aging. Cow placenta is an abundant resource with a large mass, which has not been harnessed effectively. Cow placenta extract (CPE) has the functions of antioxidation, anti-inflammatory, promoting growth and development, and promoting hair growth. However, little is known about the effect of oral administration of cow placenta extract on skin conditions. Therefore, the present study aimed to investigate the antioxidant capacity of CPE in vitro and in vivo and its protective effect on d-galactose (D-gal) induced skin aging in mice. The results showed that CPE had strong free radical scavenging, reducing and metal chelating activities. CPE can increase the activity of catalase (CAT), glutathione peroxidase (GSH-Px), peroxidase (POD), superoxide dismutase (SOD), and the content of glutathione (GSH), decrease the content of malondialdehyde (MDA). Moreover, CPE can decrease the gene and protein expression of matrix metalloproteinase 1a (MMP-1a) and matrix metalloproteinase 3 (MMP-3) and increase the expression of transforming growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase 1 (TIMP-1) of mouse skin. Histopathological analysis showed CPE reduced the collagen damage caused by D-gal, increased collagen synthesis and reduced its degradation to delay skin aging.
Dietary Behavior and Diet Interventions among Structural Firefighters: A Narrative Review
Authors: Joe Margaux J. , Hatsu Irene E. , Tefft Ally , Mok Sarah , Adetona Olorunfemi
Published: November 2022

Structural firefighters (SFFs) are exposed to multiple occupational hazards that affect dietary behavior and can contribute to increased risks of cancer and cardiovascular disease compared to the United States’ general population. Dietary behavior is a feasible modification for positive health outcomes. The objectives of this narrative review are to summarize the diet behavior of SFFs, review findings of diet interventions that positively modify diet behavior, identify research gaps, and suggest recommendations for addressing those gaps. PubMed, MEDLINE, Scopus, and CABI Web of Science were searched between February 2020 and June 2022 for peer-reviewed articles. The inclusion criteria were as follows: (1) study population must include SFFs; (2) investigate diet or diet intervention among SFFs; (3) report results specific to SFFs; and (4) be published in the English language. Thirty-four studies were included. Results indicate that SFFs recognize the importance of a healthy dietary pattern, but do not follow one, and that food choices are often influenced by colleagues. Diet interventions, such as the Mediterranean diet, were observed to have positive health improvements, such as improved lipid levels and lower CVD risk. Team counseling was found to be more effective for adopting healthier diets compared to one-on-one counseling; and general counseling was more effective than no counseling. A gap identified by this review is the lack of information concerning differences in dietary intake, diet quality, and dietary behaviors while on- and off-shift, and throughout the career. Diet is an important risk factor for occupational disease development; therefore, effective, consistent dietary interventions are necessary.
Left Ventricular Diastolic Dysfunction in Chronic Kidney Disease Patients Not Treated with Dialysis
Authors: Romejko Katarzyna , Rymarz Aleksandra , Szamotulska Katarzyna , Bartoszewicz Zbigniew , Rozmyslowicz Tomasz , Niemczyk Stanisław
Published: November 2022

Background: Left ventricular diastolic dysfunction (LVDD) is observed in the early stages of chronic kidney disease (CKD) and may lead to heart failure with preserved ejection fraction (HFpEF). The purpose of our study was to investigate the association between metabolic, nutritional and inflammatory parameters and LVDD in CKD and non-CKD patients. Methods: Two groups of patients were recruited to the study: 93 men with CKD and eGFR lower than 60 mL/min/1.73 m2 and 40 men without kidney function decrease with eGFR ≥ 60 mL/min/1.73 m2. Transthoracic echocardiography was performed to evaluate the diastolic function of the left ventricle. Bioimpedance spectroscopy (BIS) was used to measure overhydration and lean body mass. We also measured the serum concentrations of albumin, glucose, haemoglobin A1c (HgbA1c), fibrinogen, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and osteoprotegerin (OPG). Results: We observed that elevated serum fibrinogen and glucose concentrations were associated with LVDD independently of CKD status. Serum fibrinogen concentrations increased with the advancement of LVDD. Low albumin concentrations in CKD were related with LVDD. In the control group, lower muscle mass presented as lean tissue index (LTI) and lean tissue mass (LTM), and overhydration were associated with LVDD. In the group of patients without kidney function decrease the OPG concentrations were significantly higher in those with LVDD, and they rose with the advancement of LVDD. Conclusions: Elevated inflammatory parameters, increased serum glucose concentrations and worse nutritional status are the states that may impair the diastolic function of the left ventricle in CKD and non-CKD patients. Serum OPG levels are elevated in patients without kidney function decrease and LVDD and its concentrations rise with the advancement of LVDD.
Ascophyllum nodosum and Fucus vesiculosus Extracts Improved Lipid Metabolism and Inflammation in High-Energy Diet–Induced Hyperlipidemia Rats
Authors: Tung Yu-Tang , Wu Chieh-Hsi , Chen Wen-Chao , Pan Chun-Hsu , Chen Yi-Wen , Tsao Shu-Ping , Chen Chia-Jung , Huang Hui-Yu
Published: November 2022

Ascophyllum nodosum and Fucus vesiculosus both contain unique polyphenols called phlorotannins. Phlorotannins reportedly possess various pharmacological activities. A previous study reported that the activity of phlorotannin is strongly correlated with the normalization of metabolic function, and phlorotannins are extremely promising nutrients for use in the treatment of metabolic syndrome. To date, no study has explored the antihyperlipidemic effects of phlorotannins from A. nodosum and F. vesiculosus in animal models. Therefore, in the present study, we investigated the effects of phlorotannins using a rat model of high-energy diet (HED)-induced hyperlipidemia. The results showed that the rats that were fed an HED and treated with phlorotannin-rich extract from A. nodosum and F. vesiculosus had significantly lower serum fasting blood sugar (FBS), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol (TC), triacylglyceride (TG) and free fatty acids (FFAs) levels and hepatic TG level and had higher serum insulin, high-density lipoprotein cholesterol (HDL-C) levels and lipase activity in their fat tissues than in the case with the rats that were fed the HED alone. A histopathological analysis revealed that phlorotannin-rich extract could significantly reduce the size of adipocytes around the epididymis. In addition, the rats treated with phlorotannin-rich extract had significantly lowered interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels and increased superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities than did those in the HED group. These results suggested that the phlorotannin-rich extract stimulated lipid metabolism and may have promoted lipase activity in rats with HED-induced hyperlipidemia. Our results indicated that A. nodosum and F. vesiculosus, marine algae typically used as health foods, have strong antihyperlipidemic effects and may, therefore, be useful for preventing atherosclerosis. These algae may be incorporated into antihyperlipidemia pharmaceuticals and functional foods.
Effect of Single Nucleotide Polymorphisms in the Vitamin D Metabolic Pathway on Susceptibility to Non-Small-Cell Lung Cancer
Authors: Pineda Lancheros Laura Elena , Rojo Tolosa Susana , Gálvez Navas José María , Martínez Martínez Fernando , Sánchez Martín Almudena , Jiménez Morales Alberto , Pérez Ramírez Cristina
Published: November 2022

The pathogenesis of non-small-cell lung cancer (NSCLC) is complex, since many risk factors have been identified. Recent research indicates that polymorphisms in the metabolic pathway of vitamin D may be involved in both risk and survival of the disease. The objective of this study is to assess the effect of 13 genetic polymorphisms involved in the vitamin D metabolic pathway on the risk of suffering from NSCLC. We conducted an observational case-control study, which included 204 patients with NSCLC and 408 controls, of Caucasian origin, from southern Spain. The CYP27B1 (rs4646536, rs3782130, rs703842, rs10877012), CYP2R1 (rs10741657), GC (rs7041), CYP24A1, and VDR (BsmI, Cdx-2, FokI, ApaI, TaqI) gene polymorphisms were analyzed by real-time polymerase chain reaction. The logistic regression model, adjusted for smoking and family history of cancer, revealed that in the genotypic model, carriers of the VDR BsmI rs1544410-AA genotype were associated with a lower risk of developing NSCLC compared to the GG genotype (p = 0.0377; OR = 0.51; CI95% = 0.27–0.95; AA vs. GG). This association was maintained in the recessive model (p = 0.0140). Haplotype analysis revealed that the AACATGG and GACATGG haplotypes for the rs1544410, rs7975232, rs731236, rs4646536, rs703842, rs3782130, and rs10877012 polymorphisms were associated with a lower risk of NSCLC (p = 0.015 and p = 0.044 respectively). The remaining polymorphisms showed no effect on susceptibility to NSCLC. The BsmI rs1544410 polymorphism was significantly associated with lower risk of NSCLC and could be of considerable value as a predictive biomarker of the disease.
Anti-Inflammatory Protein Isolated from Tamarind Promotes Better Histological Aspects in the Intestine Regardless of the Improvement of Intestinal Permeability in a Preclinical Study of Diet-Induced Obesity
Authors: Lima Mayara S. R. , Gonçalves Catarina , Neto Mafalda D. , Macedo Maria Helena , Queiroz Jaluza L. C. de , da Silva Valéria C. , Costa Izael de S. , Camillo Christina da S. , Santos Pedro Paulo de A. , Lima Aldo A. M. , Pastrana Lorenzo , Maciel Bruna L. L. , Morais Ana Heloneida A.
Published: November 2022

Obesity is associated with metabolic and physiological effects in the gut. In this study, we evaluated the anti-inflammatory effect of trypsin inhibitor isolated from tamarind seeds (TTI) in vitro (interaction with lipopolysaccharide (LPS) and inhibitory activity against human neutrophil elastase (HNE)), and using intestinal co-cultures of Caco-2:HT29-MTX cell lines inflamed with TNF-α (50 ng/mL) and a Wistar rat model of diet-induced obesity (n = 15). TTI was administered to animals by gavage (10 days), and the treated group (25 mg/kg/day) was compared to animals without treatment or treated with a nutritionally adequate diet. In the in vitro study, it showed inhibitory activity against HNE (93%). In co-cultures, there was no protection or recovery of the integrity of inflamed cell monolayers treated with TTI (1.0 mg/mL). In animals, TTI led to lower plasma concentrations of TNF-α and IL-6, total leukocytes, fasting glucose, and LDL-c (p < 0.05). The intestines demonstrated a lower degree of chronic enteritis, greater preservation of the submucosa, and greater intestinal wall thickness than the other groups (p = 0.042). Therefore, the better appearance of the intestine not reflected in the intestinal permeability added to the in vitro activity against HNE point to possibilities for new studies and applications related to this activity.
A Prospective Study on the Relationship between Iron Supplement Intake, Hemoglobin Concentration, and Risk of Parkinsonism
Authors: Takeuchi Hikaru , Kawashima Ryuta
Published: November 2022

The findings regarding whether the greater iron level or intake is a risk factor to Parkinson’s disease (PD) or parkinsonism was not clear. The purpose of this study is to establish a consistent association between iron supplementation and parkinsonism risk, we conducted a large-scale prospective cohort study using comprehensive longitudinal data from the UK Biobank. The longitudinal cohort data of 385,898 participants (including 911 cases) who were middle to old aged British adults and joined the UK Biobank study from 2006 to 2010 and were followed up until 2018 was analyzed. The associations between iron supplement intake, hemoglobin levels and all cause subsequent parkinsonism risk after corrections of potential confounders (sex, age, household income, education length, employment status, deprivation level, body mass index, physical activity level, household numbers, smoking and drinking levels, health status, blood pressure) were investigated. Analyses revealed that (a) iron supplementation was significantly associated with higher parkinsonism risk, (b) greater hemoglobin was weakly and insignificantly associated with lower parkinsonism risk, and (c) multivitamin or vitamin C supplement intake was not significantly associated with parkinsonism risk. Regardless of whether the subjects were classified as anemic, normal, or polycythemic or in the hemoglobin level quintile, there was no nonlinear association between hemoglobin and parkinsonism risk. Parkinsonism risk did not differ between participants reporting supplementary iron intake with or without vitamin C or multivitamin supplement intake. Furthermore, polygenic risk score of PD negatively correlated with hemoglobin level, while it did not associate with intake of iron supplement or multivitamin or vitamin C supplement intake. The results suggest excessive iron intake may increase parkinsonism risk. Interventional studies are warranted to examine whether iron intake restriction is beneficial for individuals without clinical iron deficiency.
Associations of Liver Function Parameters with New-Onset Hyperuricemia in a Large Taiwanese Population Study
Authors: Lu Chun-Chi , Liu Yi-Hsueh , Lee Wen-Hsien , Chen Szu-Chia , Su Ho-Ming
Published: November 2022

Hyperuricemia is the chief cause of gout and has been linked with hypertension, cardiovascular and renal disease, diabetes and metabolic syndrome. Liver with the highest protein expression of xanthine oxidase, the main enzyme responsible for uric acid formation, is the primary site of uric acid biosynthesis. However, there are few studies that examine the association between liver function and new-onset hyperuricemia. Hence, using the Taiwan Biobank dataset, we aimed to explore the capability of liver function parameters, including gamma-glutamyl transferase, total bilirubin, albumin, alanine aminotransferase and aspartate aminotransferase in association with the subsequent development of hyperuricemia. We analyzed 21,030 participants without hyperuricemia at baseline. Hyperuricemia was defined as a uric acid concentration > 6.0 mg/dL in women or >7.0 mg/dL in men. New-onset hyperuricemia was defined as participants without baseline hyperuricemia having developed hyperuricemia upon subsequent exam. Overall, 1804 (8.6%) of the study subjects developed new-onset hyperuricemia. After multivariable analysis, significant associations were found between the male sex (odds ratio [OR], 4.412; p < 0.001), high values of systolic blood pressure (SBP) (OR, 1.006; p = 0.012), body mass index (BMI) (OR, 1.064; p < 0.001), fasting glucose (OR, 1.005; p < 0.001), triglycerides (OR, 1.001; p = 0.003), uric acid (OR, 5.120; p < 0.001), low values of estimated glomerular filtration rates (eGFR) (OR, 0.995; p < 0.001), total bilirubin (OR, 0.616; p < 0.001) and new-onset hyperuricemia. The cutoff level of total bilirubin, according to the Youden index, of receiver operating characteristic curve for identifying new-onset hyperuricemia was 0.65 mg/dL. Low total bilirubin was defined as ≤0.65 mg/dL. After multivariable analysis, we found a significant association between low total bilirubin level (≤0.65 mg/dL) (OR = 0.806; p < 0.001) and new-onset hyperuricemia. Our present study demonstrated that in addition to male sex, high SBP, BMI, fasting glucose, triglycerides, and uric acid and low eGFR, the serum’s total bilirubin levels were negatively associated with new-onset hyperuricemia in a large Taiwanese cohort.
Small-Scale Randomized Controlled Trial to Explore the Impact of β-Hydroxy-β-Methylbutyrate Plus Vitamin D3 on Skeletal Muscle Health in Middle Aged Women
Authors: Fairfield William D. , Minton Dennis M. , Elliehausen Christian J. , Nichol Alexander D. , Cook Taylor L. , Rathmacher John A. , Pitchford Lisa M. , Paluska Scott A. , Kuchnia Adam J. , Allen Jacob M. , Konopka Adam R.
Published: November 2022

β-Hydroxy-β-methylbutyrate (HMB), a leucine metabolite, can increase skeletal muscle size and function. However, HMB may be less effective at improving muscle function in people with insufficient Vitamin D3 (25-OH-D < 30 ng/mL) which is common in middle-aged and older adults. Therefore, we tested the hypothesis that combining HMB plus Vitamin D3 (HMB + D) supplementation would improve skeletal muscle size, composition, and function in middle-aged women. In a double-blinded fashion, women (53 ± 1 yrs, 26 ± 1 kg/m2, n = 43) were randomized to take placebo or HMB + D (3 g Calcium HMB + 2000 IU D per day) during 12 weeks of sedentary behavior (SED) or resistance exercise training (RET). On average, participants entered the study Vitamin D3 insufficient while HMB + D increased 25-OH-D to sufficient levels after 8 and 12 weeks. In SED, HMB + D prevented the loss of arm lean mass observed with placebo. HMB + D increased muscle volume and decreased intermuscular adipose tissue (IMAT) volume in the thigh compared to placebo but did not change muscle function. In RET, 12-weeks of HMB + D decreased IMAT compared to placebo but did not influence the increase in skeletal muscle volume or function. In summary, HMB + D decreased IMAT independent of exercise status and may prevent the loss or increase muscle size in a small cohort of sedentary middle-aged women. These results lend support to conduct a longer duration study with greater sample size to determine the validity of the observed positive effects of HMB + D on IMAT and skeletal muscle in a small cohort of middle-aged women.
DHA- and EPA-Enriched Phosphatidylcholine Suppress Human Lung Carcinoma 95D Cells Metastasis via Activating the Peroxisome Proliferator-Activated Receptor γ
Authors: Yin Haowen , Liu Yuanyuan , Yue Hao , Tian Yingying , Dong Ping , Xue Changhu , Zhao Yun-Tao , Zhao Zifang , Wang Jingfeng
Published: November 2022

The antineoplastic effects of docosahexaenoic acid-containing phosphatidylcholine (DHA-PC) and eicosapentaenoic acid-containing phosphatidylcholine (EPA-PC) were explored, and their underlying mechanisms in the human lung carcinoma 95D cells (95D cells) were investigated. After treatment of 95D cells with DHA-PC or EPA-PC, cell biological behaviors such as growth, adhesion, migration, and invasion were studied. Immunofluorescence and western blotting were carried out to assess underlying molecular mechanisms. Results showed that 95D cells proliferation and adherence in the DHA-PC or EPA-PC group were drastically inhibited than the control group. DHA-PC and EPA-PC suppressed the migration and invasion of 95D cells by disrupting intracellular F-actin, which drives cell movement. The protein expression of PPARγ was induced versus the control group. Furthermore, critical factors related to invasion, including matrix metallopeptidase 9 (MMP9), heparanase (Hpa), and vascular endothelial growth factor (VEGF), were drastically downregulated through the PPARγ/NF-κB signaling pathway. C-X-C chemokine receptor type 4 (CXCR4) and cofilin were significantly suppressed via DHA-PC and EPA-PC through the PPARγ/phosphatase and tensin homolog (PTEN)/serine-threonine protein kinase (AKT) signaling pathway. DHA-PC and EPA-PC reversed the PPARγ antagonist GW9662-induced reduction of 95D cells in migration and invasion capacity, suggesting that PPARγ was directly involved in the anti-metastasis efficacy of DHA-PC and EPA-PC. In conclusion, DHA-PC and EPA-PC have great potential for cancer therapy, and the antineoplastic effects involve the activation of PPARγ. EPA-PC showed more pronounced antineoplastic effects than DHA-PC, possibly due to the more robust activation of PPARγ by EPA-PC.
The Troublesome Ticks Research Protocol: Developing a Comprehensive, Multidiscipline Research Plan for Investigating Human Tick-Associated Disease in Australia
Authors: Barbosa Amanda D. , Long Michelle , Lee Wenna , Austen Jill M. , Cunneen Mike , Ratchford Andrew , Burns Brian , Kumarasinghe Prasad , Ben-Othman Rym , Kollmann Tobias R. , Stewart Cameron R. , Beaman Miles , Parry Rhys , Hall Roy , Tabor Ala , O’Donovan Justine , Faddy Helen M. , Collins Marjorie , Cheng Allen C. , Stenos John , Graves Stephen , Oskam Charlotte L. , Ryan Una M. , Irwin Peter J.
Published: November 2022

In Australia, there is a paucity of data about the extent and impact of zoonotic tick-related illnesses. Even less is understood about a multifaceted illness referred to as Debilitating Symptom Complexes Attributed to Ticks (DSCATT). Here, we describe a research plan for investigating the aetiology, pathophysiology, and clinical outcomes of human tick-associated disease in Australia. Our approach focuses on the transmission of potential pathogens and the immunological responses of the patient after a tick bite. The protocol is strengthened by prospective data collection, the recruitment of two external matched control groups, and sophisticated integrative data analysis which, collectively, will allow the robust demonstration of associations between a tick bite and the development of clinical and pathological abnormalities. Various laboratory analyses are performed including metagenomics to investigate the potential transmission of bacteria, protozoa and/or viruses during tick bite. In addition, multi-omics technology is applied to investigate links between host immune responses and potential infectious and non-infectious disease causations. Psychometric profiling is also used to investigate whether psychological attributes influence symptom development. This research will fill important knowledge gaps about tick-borne diseases. Ultimately, we hope the results will promote improved diagnostic outcomes, and inform the safe management and treatment of patients bitten by ticks in Australia.
Host-Directed Therapies for Tuberculosis
Authors: Jeong Eui-Kwon , Lee Hyo-Ji , Jung Yu-Jin
Published: November 2022

Tuberculosis (TB) is one of the leading causes of death worldwide, consistently threatening public health. Conventional tuberculosis treatment requires a long-term treatment regimen and is associated with side effects. The efficacy of antitubercular drugs has decreased with the emergence of drug-resistant TB; therefore, the development of new TB treatment strategies is urgently needed. In this context, we present host-directed therapy (HDT) as an alternative to current tuberculosis therapy. Unlike antitubercular drugs that directly target Mycobacterium tuberculosis (Mtb), the causative agent of TB, HDT is an approach for treating TB that appropriately modulates host immune responses. HDT primarily aims to enhance the antimicrobial activity of the host in order to control Mtb infection and attenuate excessive inflammation in order to minimize tissue damage. Recently, research based on the repositioning of drugs for use in HDT has been in progress. Based on the overall immune responses against Mtb infection and the immune-evasion mechanisms of Mtb, this review examines the repositioned drugs available for HDT and their mechanisms of action.
Prevalence of Non-SARS-CoV-2 Respiratory Pathogens and Co-Infection with SARS-CoV-2 in the Early Stage of COVID-19 Epidemic
Authors: Han Huimin , Saed Yasin Abdi , Song Wenzhu , Wang Ming , Li Yafeng
Published: November 2022

Background: This study aims to reflect the prevalence of non-SARS-CoV-2 respiratory pathogens and co-infection with SARS-CoV-2 in the early stage of the COVID-19 epidemic, considering SARS-CoV-2 broke out during influenza season and its symptoms resemble those of influenza. Methods: A total of 685 nucleic acid samples of respiratory pathogens were collected from 1 November 2019 to 20 January 2020 and were detected by the 13 Respiratory Pathogen Multiplex Detection Kit and Novel Coronavirus (2019-nCoV) Nucleic Acid Diagnostic Kit. Results: In Wuhan, human rhinovirus was the most frequent infectious pathogen in November (31.5%) and human respiratory syncytial virus appeared the most in December and January (37.1%, 8.6%, respectively). Detection of SARS-CoV-2 first appeared from January 1 to January 10. Generally, 115 patients of 616 patients (18.7%) from Wuhan were infected with SARS-CoV-2, and only two children were co-infected with other respiratory pathogens. In Taiyuan, influenza A virus was detected most frequently in December and January (30.3%, 12%, respectively) without infection of SARS-CoV-2. Conclusions: Some cases diagnosed with influenza before routine nucleic acid testing of SARS-CoV-2 were attributed to COVID-19. Co-infection between SARS-CoV-2 and other non-SARS-CoV-2 respiratory pathogens existed in the early stage of COVID-19 epidemic.
Resistance to Cypermethrin Is Widespread in Cattle Ticks (Rhipicephalus microplus) in the Province of Punjab, Pakistan: In Vitro Diagnosis of Acaricide Resistance
Authors: Sindhu Zia ud Din , Naseer Muhammad Usman , Raza Ali , Aslam Bilal , Ahmad Javed , Abbas Rao Zahid , Khan Muhammad Kasib , Imran Muhammad , Zafar Muhammad Arif , Khattak Baharullah
Published: November 2022

Control of the cattle tick Rhipicephalus (R.) microplus mainly relies on chemical acaricides and cypermethrin is the most widely used acaricide in Pakistan. Farmers frequently complain about its low efficacy, thus, the present study was designed to quantify the frequency of cypermethrin resistance in cattle ticks. Engorged female R. microplus were collected and tested for the efficacy of cypermethrin using the FAO-recommended larval packet test. Resistance factors (RF) were estimated at both the lethal concentration for 50% (LC50) and 99% (LC99) of ticks. Thirty-three samples were tested, of which 8/33 (24.24%) were classified as resistant based on the RF50, and all 33 were classified as resistant based on the RF99. In District Sargodha, when only the RF50 was considered, 45.5% of samples were classified as resistant, but at RF99, all tested samples were identified as resistant. In District Okara, the variation in RF50 estimates was 2.2–8.3 and variation in RF99 estimates was 10.6–1139.8. Similar results were found in District Attock, where variations in RF50 were 0.8–8.5 and RF99 ranged from 9–237.3. The study showed that cypermethrin resistance is prevalent in these three districts of Pakistan and is likely to be overestimated by classification based on the RF99.
Clinical Impact of Colonization with Carbapenem-Resistant Gram-Negative Bacteria in Critically Ill Patients Admitted for Severe Trauma
Authors: Ceccarelli Giancarlo , Alessandri Francesco , Moretti Sonia , Borsetti Alessandra , Maggiorella Maria Teresa , Fabris Silvia , Russo Alessandro , Ruberto Franco , De Meo Daniele , Ciccozzi Massimo , Mastroianni Claudio M. , Venditti Mario , Pugliese Francesco , d’Ettorre Gabriella
Published: November 2022

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) have raised concerns as common, frequent etiologic agents of nosocomial infections, and patients admitted to intensive care units (ICUs) present the highest risk for colonization and infection. The incidence of colonization and infection in trauma patients remains poorly investigated. The aim of this study was to assess the risk factors for Carbapenem-resistant (CR)-GNB colonization and the clinical impact of colonization acquisition in patients with severe trauma admitted to the ICU in a CR-GNB hyperendemic country. This is a retrospective observational study; clinical and laboratory data were extracted from the nosocomial infection surveillance system database. Among 54 severe trauma patients enrolled in the study, 28 patients were colonized by CR-GNB; 7 (12.96%) patients were already colonized at ICU admission; and 21 (38.89%) patients developed a new colonization during their ICU stay. Risk factors for colonization were the length of stay in the ICU (not colonized, 14.81 days ± 9.1 vs. colonized, 38.19 days ± 27.9; p-value = 0.001) and days of mechanical ventilation (not colonized, 8.46 days ± 7.67 vs. colonized, 22.19 days ± 15.09; p-value < 0.001). There was a strong statistical association between previous colonization and subsequent development of infection (OR = 80.6, 95% CI 4.5–1458.6, p-value < 0.001). Factors associated with the risk of infection in colonized patients also included a higher Charlson comorbidity index, a longer length of stay in the ICU, a longer duration of mechanical ventilation, and a longer duration of treatment with carbapenem and vasopressors (not infected vs. infected: 0(0–4) vs. 1(0–3), p = 0.012; 24.82 ± 16.77 vs. 47 ± 28.51, p = 0.016; 13.54 ± 15.84 vs. 31.7 ± 16.22, p = 0.008; 1.09 ± 1.14 vs. 7.82 ± 9.15, p = 0.008). The adoption of MDR-GNB colonization prevention strategies in critically ill patients with severe trauma is required to improve the quality of care and reduce nosocomial infections, length of hospital stay and mortality.