bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bio-Indicator Pilot Study Screening Selected Heavy Metals in Female Hair, Nails, and Serum from Lifestyle Cosmetic, Canned Food, and Manufactured Drink Choices
Authors: Hamouda Asmaa Fathi , Felemban Shifa
Published: July 2023

Lifestyles, genetic predispositions, environmental factors, and geographical regions are considered key factors of heavy metals initiatives related to health issues. Heavy metals enter the body via the environment, daily lifestyle, foods, beverages, cosmetics, and other products. The accumulation of heavy metals in the human body leads to neurological issues, carcinogenesis, failure of multiple organs in the body, and a reduction in sensitivity to treatment. We screened for Cr, Al, Pb, and Cd in selected foods, beverages, and cosmetics products depending on questionnaire outcomes from female volunteers. We also screened for Cr, Al, Pb, and Cd on hair, nails, and serum samples using inductively coupled plasma mass spectrometry (ICP-MS) from the same volunteers, and we analyzed the serum cholinesterase and complete blood picture (CBC). We performed an AutoDock study on Cr, Al, Pb, and Cd as potential ligands. Our results indicate that the most elevated heavy metal in the cosmetic sample was Al. In addition, in the food and beverages samples, it was Pb and Al, respectively. The results of the questionnaire showed that 71 percent of the female volunteers used the studied cosmetics, food, and beverages, which were contaminated with Cr, Al, Pb, and Cd, reflecting the high concentration of Cr, Al, Cd, and Pb in the three different types of biological samples of sera, nails, and hair of the same females, with 29 percent of the female volunteers not using the products in the studied samples. Our results also show an elevated level of cholinesterase in the serum of group 1 that was greater than group 2, and this result was confirmed by AutoDock. Moreover, the negative variation in the CBC result was compared with the reference ranges. Future studies should concentrate on the actions of these heavy metal contaminations and their potential health consequences for various human organs individually.
Ultra-High-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry for Simultaneous Pesticide Analysis and Method Validation in Sweet Pepper
Authors: Bang Han Yeol , Kim Yong-Kyoung , Kim Hyoyoung , Baek Eun Joo , Na Taewoong , Sim Kyu Sang , Kim Ho Jin
Published: July 2023

Pesticides effectively reduce the population of various pests that harm crops and increase productivity, but leave residues that adversely affect health and the environment. Here, a simultaneous multicomponent analysis method based on ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) pretreated by the QuEChERS method was developed to control the maximum residual levels. Among the 140 pesticides with high frequency of detection in agricultural products in Gyeongnam region in Korea for 5 years, 12 pesticides with high detection frequency in sweet pepper were selected. The analytical method is validated, linearities are r2 > 0.999, limit of detection (LOD) ranges from 1.4 to 3.2 µg/kg, and limit of quantification (LOQ) ranges from 4.1 to 9.7 µg/kg, and the recovery rate was 81.7–99.7%. In addition, it was confirmed that a meaningful value of these parameters can be achieved by determining the measurement uncertainty. The results proved that parameters such as recovery rate and relative standard deviation of the analysis method were within international standards. Using the developed method, better and safer sweet peppers will be provided to consumers, and effective pesticide residue management will be possible by expanding to other agricultural products.
Anti-Inflammatory and Antioxidant Effects of Diosmetin-3-O-β-d-Glucuronide, the Main Metabolite of Diosmin: Evidence from Ex Vivo Human Skin Models
Authors: Boisnic Sylvie , Branchet Marie-Christine , Quioc-Salomon Barbara , Doan Julie , Delva Catherine , Gendron Célia
Published: July 2023

Diosmin is used to relieve chronic venous disease (CVD) symptoms. This study aimed to investigate the anti-inflammatory and antioxidant effects of diosmetin-3-O-β-d-glucuronide, the major metabolite of diosmin, using human skin explants. The explants were exposed to substance P (inflammation model) or UVB irradiation (oxidative model) and to five diosmetin-3-O-β-d-glucuronide concentrations. Inflammation was evaluated through interleukin-8 (IL-8) secretion measurements and capillary dilation observation, and oxidation was evaluated by measuring the hydrogen peroxide levels and observing cyclobutane pyrimidine dimers (CPDs). In substance-P-exposed explants, diosmetin-3-O-β-d-glucuronide induced a significant decrease in IL-8 secretions, with a maximal effect at 2700 pg/mL (−49.6%), and it reduced the proportion of dilated capillaries and the mean luminal cross-sectional area (p < 0.0001 at all tested concentrations), indicating a vasoconstrictive effect. In UVB-irradiated fragments, diosmetin-3-O-β-d-glucuronide induced a significant decrease in hydrogen peroxide production and in the number of CPD-positive cells, reaching a maximal effect at the concentration of 2700 pg/mL (−48.6% and −52.0%, respectively). Diosmetin-3-O-β-d-glucuronide induced anti-inflammatory and antioxidant responses, with the maximal effect being reached at 2700 pg/mL and corresponding to the peak plasma concentration estimated after the oral intake of 600 mg of diosmin, the daily dose usually recommended for the treatment of CVD. These ex vivo findings suggest a protective role of diosmetin-3-O-β-d-glucuronide against inflammatory and oxidative stress affecting the vascular system in CVD pathophysiology.
Evaluation of the Effect of Ultrasonic Pretreatment on the Drying Kinetics and Quality Characteristics of Codonopsis pilosula Slices Based on the Grey Correlation Method
Authors: Wang Tongxun , Ying Xinyu , Zhang Qian , Xu Yanrui , Jiang Chunhui , Shang Jianwei , Zang Zepeng , Wan Fangxin , Huang Xiaopeng
Published: July 2023

Ultrasonic (US) maltreatment was performed before the vacuum far-infrared drying (VFID) of Codonopsis pilosula (CP) slices to investigate the effects of different US parameters on the drying characteristics and nutrients of CP slices. The grey correlation method with relative correlation degree (ri) as the evaluation measure was used to construct a model for the evaluation of the pretreatment quality of CP and to determine the optimal pretreatment conditions. The results showed that with the increase in US frequency and power, the drying rate increased. Under the conditions of US power of 180 W, frequency of 60 kHz and a pre-treatment time of 30 min, the drying time reduced by 28.6%. The contents of polysaccharide and syringin in dried CP slices pretreated by US increased by 14.7% and 62.0%, respectively, compared to the non-pre-treated samples, while the total flavonoid content decreased by 10.0%. In terms of colour, pretreatment had a certain protective effect on the red colour of dried products. The highest relative correlation (0.574) and the best overall quality of performance were observed at 180 W, 60 kHz and 30 min. Overall, US technology is suitable for the pretreatment processing of CP, which is of great significance to the drying of CP.
MSN8C: A Promising Candidate for Antitumor Applications as a Novel Catalytic Inhibitor of Topoisomerase II
Authors: Ou Jie-Bin , Huang Wei-Hao , Liu Xing-Zi , Dai Guo-Yao , Wang Lu , Huang Zhi-Shu , Huang Shi-Liang
Published: July 2023

MSN8C, an analog of mansonone E, has been identified as a novel catalytic inhibitor of human DNA topoisomerase II that induces tumor regression and differs from VP-16(etoposide). Treatment with MSN8C showed significant antiproliferative activity against eleven human tumor cell lines in vitro. It was particularly effective against the HL-60/MX2 cell line, which is resistant to Topo II poisons. The resistance factor (RF) of MSN8C for Topo II in HL-60/MX2 versus HL-60 was 1.7, much lower than that of traditional Topo II poisons. Furthermore, in light of its potent antitumor efficacy and low toxicity, as demonstrated in the A549 tumor xenograft model, MSN8C has been identified as a promising candidate for antitumor applications.
A First-Class Degrader Candidate Targeting Both KRAS G12D and G12V Mediated by CANDDY Technology Independent of Ubiquitination
Authors: Miyamoto-Sato Etsuko , Imanishi Satoshi , Huang Lijuan , Itakura Shoko , Iwasaki Yoichi , Ishizaka Masamichi
Published: July 2023

“Undruggable” targets such as KRAS are particularly challenging in the development of drugs. We devised a novel chemical knockdown strategy, CANDDY (Chemical knockdown with Affinity aNd Degradation DYnamics) technology, which promotes protein degradation using small molecules (CANDDY molecules) that are conjugated to a degradation tag (CANDDY tag) modified from proteasome inhibitors. We demonstrated that CANDDY tags allowed for direct proteasomal target degradation independent of ubiquitination. We synthesized a KRAS-degrading CANDDY molecule, TUS-007, which induced degradation in KRAS mutants (G12D and G12V) and wild-type KRAS. We confirmed the tumor suppression effect of TUS-007 in subcutaneous xenograft models of human colon cells (KRAS G12V) with intraperitoneal administrations and in orthotopic xenograft models of human pancreatic cells (KRAS G12D) with oral administrations. Thus, CANDDY technology has the potential to therapeutically target previously undruggable proteins, providing a simpler and more practical drug targeting approach and avoiding the difficulties in matchmaking between the E3 enzyme and the target.
Modification of the 4-Hydroxyphenylacetate-3-hydroxylase Substrate Pocket to Increase Activity towards Resveratrol
Authors: Zhang Qianchao , Jin Yuning , Yang Kai , Hu Sheng , Lv Changjiang , Huang Jun , Mei Jiaqi , Zhao Weirui , Mei Lehe
Published: July 2023

4-Hydroxyphenylacetate-3-hydroxylase (4HPA3H; EC 1.14.14.9) is a heterodimeric flavin-dependent monooxygenase complex that catalyzes the ortho-hydroxylation of resveratrol to produce piceatannol. Piceatannol has various health benefits and valuable applications in food, medicine, and cosmetics. Enhancing the catalytic activity of 4HPA3H toward resveratrol has the potential to benefit piceatannol production. In this study, the critical amino acid residues in the substrate pocket of 4HPA3H that affect its activity toward resveratrol were identified using semi-rational engineering. Two key amino acid sites (I157 and A211) were discovered and the simultaneous “best” mutant I157L/A211D enabled catalytic efficiency (Kcat/Km—resveratrol) to increase by a factor of 4.7-fold. Molecular dynamics simulations indicated that the increased flexibility of the 4HPA3H substrate pocket has the potential to improve the catalytic activity of the enzyme toward resveratrol. On this basis, we produced 3.78 mM piceatannol by using the mutant I157L/A211D whole cells. In this study, we successfully developed a highly active 4HPA3H variant for the hydroxylation of resveratrol to piceatannol.
Effects of Desert Olive Tree Pearls Containing High Hydroxytyrosol Concentrations on the Cognitive Functions of Middle-Aged and Older Adults
Authors: Yoon Jieun , Sasaki Kazunori , Nishimura Iku , Hashimoto Haruna , Okura Tomohiro , Isoda Hiroko
Published: July 2023

The Japanese population has the world’s longest life expectancy but faces the challenge of extending the healthy life expectancy without developing chronic diseases. Therefore, the effectiveness of products derived from olives used in the Mediterranean diet as a potential dietary solution has attracted attention. This study examined the effects of desert olive tree pearls (DOTPs), which contain 162 times more polyphenol hydroxytyrosol than olive oil, on the cognitive function of middle-aged and older adults using the Cognitrax test. Participants (aged 51–82 years) were assigned to the DOTP intake (n = 36) or placebo group (n = 36) in a randomized, double-blind, placebo-controlled, parallel-group study. The participants received 3 g of DOTPs or placebo in olive oil twice daily for 12 weeks. Among cognitive domains, complex attention had a significant time × group interaction effect (p = 0.049) between the DOTP and placebo groups. The simple main effect for this item was significantly different (p < 0.001 and p = 0.572, respectively). Time effects were significant (p < 0.05) for the psychomotor speed, reaction time, cognitive flexibility, processing speed, and executive function domains. Therefore, DOTPs have the potential to alleviate cognitive problems faced by middle-aged and older adults in Japan.
Recommendations for Nutritional Supplementation in Pediatric Oncology: A Compilation of the Facts
Authors: Podpeskar Alexandra , Crazzolara Roman , Kropshofer Gabriele , Hetzer Benjamin , Rabensteiner Evelyn , Meister Bernhard , Obexer Petra , Salvador Christina
Published: July 2023

Background: As one of the few modifiable risk factors, the importance of dietary patterns for both disease prevention and treatment outcome in pediatric oncology has gained increasing popularity. Malnutrition is associated with lower survival rates, tolerance to treatment, and quality of life. Yet, especially in children with malignancies, nutritional deterioration is common, and pediatric cancer patients often present with inadequate intake of micro- and macronutrients alike. Despite the reported widespread use of dietary supplements, few empirical data provide a basis for clinical recommendations, and evidence for their efficacy is inconsistent. Current literature lacks a systematic approach as to how and which supplements should be recommended for specific patients, types of cancer, or during specific treatments. The aim of this review is to highlight the role of the most frequently used nutrients in pediatric malignant diseases and to give a practical guide based on current scientific evidence. Methods: A comprehensive literature search was conducted on PubMed through April 2023 to select meta-analyses, systematic reviews, observational studies, and individual randomized controlled trials (RCTs) of macro- and micronutrient supplementation in pediatric oncology. The search strategy included the following medical subject headings (MeSH) and keywords: “childhood cancer”, “pediatric oncology”, “nutritional status”, “dietary supplements”, “vitamins”, “micronutrients”, “calcium”, “magnesium”, “vitamin D”, “zinc” “glutamine”, “selen”, and “omega-3 fatty acids”. The reference lists of all relevant articles were screened to include potentially pertinent studies. Results: The present review provides a comprehensive and updated overview of the latest evidence about the role of nutrition and diet in pediatric oncology, also focusing on different nutritional interventions available for the management of the disease. We summarize evidence about the importance of adequate nutrition in childhood cancer and the role of several micronutrients and critically interpret the findings. Possible effects and benefits of supplementation during chemotherapy are discussed, as are strategies for primary and secondary prevention. Conclusions: We here describe the obvious benefits of dietary supplementation for childhood cancer. Further large-scale clinical trials are required to verify the impacts of deficiencies and the possible benefits of supplementation and optimal dosages. (337 words).
Bitter Is Better: Wild Greens Used in the Blue Zone of Ikaria, Greece
Authors: Pieroni Andrea , Morini Gabriella , Piochi Maria , Sulaiman Naji , Kalle Raivo , Haq Shiekh Marifatul , Devecchi Andrea , Franceschini Cinzia , Zocchi Dauro M. , Migliavada Riccardo , Prakofjewa Julia , Sartori Matteo , Krigas Nikos , Ahmad Mushtaq , Torri Luisa , Sõukand Renata
Published: July 2023

The current study reports an ethnobotanical field investigation of traditionally gathered and consumed wild greens (Chorta) in one of the five so-called Blue Zones in the world: Ikaria Isle, Greece. Through 31 semi-structured interviews, a total of 56 wild green plants were documented along with their culinary uses, linguistic labels, and locally perceived tastes. Most of the gathered greens were described as bitter and associated with members of Asteraceae and Brassicaceae botanical families (31%), while among the top-quoted wild greens, species belonging to these two plant families accounted for 50% of the wild vegetables, which were consumed mostly cooked. Cross-cultural comparison with foraging in other areas of the central-eastern Mediterranean and the Near East demonstrated a remarkable overlapping of Ikarian greens with Cretan and Sicilian, as well as in the prevalence of bitter-tasting botanical genera. Important differences with other wild greens-related food heritage were found, most notably with the Armenian and Kurdish ones, which do not commonly feature many bitter greens. The proven role of extra-oral bitter taste receptors in the modulation of gastric emptying, glucose absorption and crosstalk with microbiota opens new ways of looking at these differences, in particular with regard to possible health implications. The present study is also an important attempt to preserve and document the bio-cultural gastronomic heritage of Chorta as a quintessential part of the Mediterranean diet. The study recommends that nutritionists, food scientists, and historians, as well as policymakers and practitioners, pay the required attention to traditional rural dietary systems as models of sustainable health.
A Mexican Spanish Adaptation of the Dutch Eating Behavior Questionnaire: Psychometric Properties and Influence of Sociodemographic Variables in Pregnant Women
Authors: Flores-Quijano María Eugenia , Mota-González Cecilia , Rozada Guadalupe , León-Rico Jacqueline Citlalli , Gómez-López María Eugenia , Vega-Sánchez Rodrigo
Published: July 2023

Eating behaviors are complex phenomena, entangling physiological signals of hunger and satiety, food choices, emotional states, and social factors and expectations, as well as food availability and sensory appearance. Evaluating eating behaviors is challenging and must cover different motives. One instrument for such evaluation is the Dutch Eating Behavior Questionnaire (DEBQ), composed of three subscales for exploring emotional eating, external eating, and restrained eating. In this article, we aimed to (1) evaluate the psychometric properties of a Mexican Spanish adaptation of the DEBQ; and (2) explore the associations between the three adapted DEBQ scales and the influence of sociodemographic factors on each of the three eating behaviors in Mexican pregnant women. A sample of 514 pregnant women responded to our adapted version of the DEBQ and a questionnaire about sociodemographic information. We performed an exploratory factor analysis using a principal component analysis with varimax rotation; based on this analysis, we removed items that loaded on two factors and then performed a confirmatory factor analysis. The final version of the adapted DEBQ has 26 items, clearly divided into a three-factor structure and satisfactorily reliable (Cronbach’s ⍺ = 0.903). We then performed Spearman bivariate correlations and multivariate linear regression with backward variable selection to test the associations and influence of sociodemographic factors on each of the three eating behaviors evaluated with the DEBQ. In pregnant women, emotional eating (EmoE) had a medium-high correlation with external eating (ExtE) and a low correlation with restrained eating (RestE), while ExtE and RestE showed no association. The three eating behaviors are associated with maternal sociodemographic and reproductive variables, which partly explain their variation, most notably maternal schooling. Our adapted version of the DEBQ is suitable for use with Mexican Spanish–speaking pregnant women. Maternal sociodemographic and reproductive factors have an influence on the variance of eating behaviors during pregnancy.
Effects of Continuous Carbohydrate Intake with Gummies during the Golf Round on Interstitial Glucose, Golf Performance, and Cognitive Performance of Competitive Golfers: A Randomized Repeated-Measures Crossover Design
Authors: Nagashima Yosuke , Ehara Kiyohiro , Ehara Yoshitomo , Mitsume Ayana , Kubo Kie , Mineo Shigeru
Published: July 2023

This study examined the effects of continuous carbohydrate intake during a golf round on interstitial glucose, golf performance, and the cognitive performance of competitive golfers. Eleven competitive golfers participated and played 18 holes of golf in this study. Participants were randomly assigned to the group indicated to consume the test food (CHO intake) or the group required to not consume it (NOT intake). Here, gummies were used as the test food, and the amount of carbohydrates was 30 g per h. Blood glucose levels were evaluated using interstitial glucose. Golf performance was measured in five tests, including scores, 2.5 m putting test, club head speed, driving distance, and accuracy. Cognitive performance was measured in three tests, including self-perceived levels of fatigue (PLF), self-perceived levels of concentration (PLC), and self-perceived levels of relaxation (PLR). Interstitial glucose (p < 0.001) and PLF (p < 0.001) were significantly reduced in the CHO intake compared with that in the NOT intake from the sixth hole. PLC was significantly higher in the CHO intake than in the NOT intake on all 18 holes (p = 0.032). These findings suggest that continuous carbohydrate intake may be effective in reducing fatigue and maintaining the performance of competitive golfers.
What Is the Role of Nutraceutical Products in Cancer Patients? A Systematic Review of Randomized Clinical Trials
Authors: Di Napoli Raffaella , Balzano Nunzia , Mascolo Annamaria , Cimmino Carla , Vitiello Antonio , Zovi Andrea , Capuano Annalisa , Boccellino Mariarosaria
Published: July 2023

Chemotherapy represents the main pharmacological cancer treatment. Recently, positive effects emerged with the combination of anticancer therapy and nutraceutical products. The aim of this systematic review is to collect and synthesize the available scientific evidence regarding the potential effects of nutraceuticals on cancer cells. A systematic literature search of randomized clinical trials of nutraceutical products in patients with cancer published up to 15 December 2022 was conducted using three data sources: Embase, PubMed, and Web of Science. The effect of high-dose isoflavone supplements on prostate cancer resulted in stabilization or reduction of PSA concentrations in 50% of isoflavone group patients six months after treatment. High doses of vitamin D supplementation plus chemotherapy in patients with advanced or metastatic colorectal cancer showed a median PFS of 13.0 months (95% CI, 10.1–14.7 months) for 49 patients. The effect of vitamin D supplementation on markers of inflammatory level and antioxidant capacity in women with breast cancer showed a significant increase in serum vitamin D concentration (28 ± 2.6 to 39 ± 3.5; p = 0.004) after 8 weeks of treatment. In conclusion, nutraceutical supplements represent a potentially growing sector and can be utilized in medical treatment or nutrition to provide integrated medical care.
Concept of an Intervention for Sustainable Weight Loss in Postmenopausal Women with Overweight—Secondary Analysis of a Randomized Dietary Intervention Study
Authors: Englert Isabell , Egert Sarah , Hoffmann Laura , Kohlenberg-Müller Kathrin
Published: July 2023

Introduction: The approach of an individual diet has great potential for sustainable weight reduction. Social support, participation and empowerment are also key factors for high motivation and compliance. So, the impact of an individual diet in combination with group sessions on weight loss in postmenopausal women with overweight was investigated. Methods: In this reanalysis of a controlled intervention study, postmenopausal women (n = 54; BMI 30.9 ± 3.4 kg/m2; 59 ± 7 years) were recruited receiving an energy restricted diet for 12 weeks, followed by a six-month follow-up phase. The women received 51 individual meal plans based on their habits and were trained in four group sessions. Results: Forty-six women completed the intervention phase, and 29 completed the follow-up. Average weight loss was −5.8 ± 3.0 kg (p < 0.001) after 12 weeks and was still significant at follow-up (−4.9 ± 5.4 kg, p < 0.001). Also, decreases in fat-free mass (−1.1 ± 1.2 kg, p < 0.001) and resting energy expenditure (−1096 ± 439 kJ/24 h, p < 0.001) were observed. Conclusions: The individual nutrition approach with a focus on nutritype in combination with group sessions was effective for long-lasting weight loss in postmenopausal women. An important factor is close individual and group support.
Association of Dietary Intake of Zinc and Selenium with Breast Cancer Risk: A Case-Control Study in Chinese Women
Authors: Tu Kexin , Liu Kaiyan , Wang Yifan , Jiang Yiling , Zhang Caixia
Published: July 2023

As major nonenzymatic antioxidant components in the body, dietary Zinc (Zn) and Selenium (Se) may have an impact on breast cancer development. This study aimed to investigate the relationship between dietary Zn, Se intake and breast cancer risk in Chinese women. The case-control study included 1591 cases and 1622 age-frequency matched controls. Dietary intake was collected using a validated food frequency questionnaire. Dietary Zn and Se were divided into four categories: Zn/Se from plants, Zn/Se from meat, Zn/Se from red meat, and Zn/Se from white meat. Unconditional logistic regression models and restricted cubic spline analyses were performed to identify potential associations. Zn from white meat intake was linearly and inversely associated with breast cancer risk, and Se from red meat intake was linearly and positively associated with breast cancer risk, with adjusted odds ratio and 95% confidence interval of 0.76 (0.61–0.95) and 1.36 (1.04–1.77), respectively. Non-linear relationships were found between total dietary Zn, Zn from meat, Zn from red meat intake and breast cancer risk (pnon-linearity < 0.05). In conclusion, dietary Zn and Se intake were associated with breast cancer risk in Chinese women, and the optimal intake of Zn may be beneficial for breast cancer prevention.
The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components
Authors: Xiong Ruo-Gu , Li Jiahui , Cheng Jin , Zhou Dan-Dan , Wu Si-Xia , Huang Si-Yu , Saimaiti Adila , Yang Zhi-Jun , Gan Ren-You , Li Hua-Bin
Published: July 2023

The number of individuals experiencing mental disorders (e.g., anxiety and depression) has significantly risen in recent years. Therefore, it is essential to seek prevention and treatment strategies for mental disorders. Several gut microbiota, especially Firmicutes and Bacteroidetes, are demonstrated to affect mental health through microbiota–gut–brain axis, and the gut microbiota dysbiosis can be related to mental disorders, such as anxiety, depression, and other mental disorders. On the other hand, dietary components, including probiotics (e.g., Lactobacillus and Bifidobacterium), prebiotics (e.g., dietary fiber and alpha-lactalbumin), synbiotics, postbiotics (e.g., short-chain fatty acids), dairy products, spices (e.g., Zanthoxylum bungeanum, curcumin, and capsaicin), fruits, vegetables, medicinal herbs, and so on, could exert protective effects against mental disorders by enhancing beneficial gut microbiota while suppressing harmful ones. In this paper, the mental disorder-associated gut microbiota are summarized. In addition, the protective effects of dietary components on mental health through targeting the gut microbiota are discussed. This paper can be helpful to develop some dietary natural products into pharmaceuticals and functional foods to prevent and treat mental disorders.
Precarious Young Adults’ Mental Health during the Pandemic: The Major Impact of Food Insecurity Independently of COVID-19 Diagnosis
Authors: Essadek Aziz , Shadili Gérard , Bergami Goulart Barbosa Pablo , Assous Adèle , Widart Frédéric , Payan Ségolène , Rabeyron Thomas , Corruble Emmanuelle , Falissard Bruno , Gressier Florence
Published: July 2023

The COVID-19 pandemic had a major impact on mental health across populations, especially young and precarious people. Furthermore, COVID-19 diagnosis itself has been associated with psychiatric symptoms. However, only a few studies have assessed the mental health of precarious youth, and examined a possible association with food insecurity, while including COVID-19 diagnosis in their analyses. We aimed to determine the prevalence of poor mental health in precarious youth during the COVID-19 pandemic, and to investigate its possible association with food insecurity, independently of COVID-19 diagnosis. In a cross-sectional study conducted in the context of an employment program for precarious youth (18–25 years) living in Paris, France, 823 individuals were assessed for depression, anxiety, subjective distress and food insecurity during the second lockdown of 2020. A directed acyclic graph (DAG)-based approach was used to identify confounders for inclusion in a multivariate regression model. Of the 823 precarious youth, 45.93% reported significant symptoms of depression, 36.69% anxiety, 39% distress and 25.39% suicidal ideation. In the multivariate analysis based on DAG, food insecurity (less than one meal per day) was associated with depression (OR = 2.30; CI%: 1.19–4.51), anxiety (OR = 2.51; CI%: 1.29–4.88), distress (OR = 2.36; CI%: 1.23–4.57) and suicidal ideation (OR = 4.81; CI%: 2.46–9.44), independently of age, gender, education, COVID-19 contact and COVID-19 diagnosis. This study highlights the importance of food insecurity on mental health among young precarious people during the COVID-19 pandemic. Reducing food insecurity is essential to help reduce psychological distress.
Adherence to the DASH Diet and Risk of Hypertension: A Systematic Review and Meta-Analysis
Authors: Theodoridis Xenophon , Chourdakis Michail , Chrysoula Lydia , Chroni Violeta , Tirodimos Ilias , Dipla Konstantina , Gkaliagkousi Eugenia , Triantafyllou Areti
Published: July 2023

The aim of this study was to assess the effect of the level of adherence to the DASH diet on hypertension risk by conducting a systematic review and meta-analysis. A systematic literature search was performed. Two independent investigators performed the study selection, data abstraction, and assessment of the included studies. The meta-analysis was performed separately with the adjusted hazard (HR) or incident rate ratios (IRR) and the odds ratios (OR) of the highest compared to the lowest DASH diet adherence scores using a random effects model. A total of 12 studies were included in the qualitative and quantitative synthesis. When cohort studies reporting HR were pooled together, high adherence to the DASH diet was associated with a lower risk of hypertension (HR: 0.81, 95% CI 0.73–0.90, I2 = 69%, PI 0.61–1.08) compared to the low adherence. When cross-sectional studies reporting OR were combined, high adherence to the DASH diet was also related to a lower risk of hypertension (OR: 0.80, 95% CI 0.70–0.91, I2 = 81%, PI 0.46–1.39). The findings suggest that high adherence to the DASH diet has a positive effect on reducing hypertension risk compared to low adherence. These data strengthen and are in line with all hypertension guidelines, indicating that lifestyle changes should start early even in populations with normal blood pressure.
Health Risk and Underweight
Authors: Cuntz Ulrich , Quadflieg Norbert , Voderholzer Ulrich
Published: July 2023

Anorexia nervosa is associated with a significant risk of morbidity and mortality. In clinical practice, health risk is assessed and estimated using routinely collected laboratory data. This study will develop a risk score using clinically relevant laboratory parameters. The related question is how to estimate the health risk associated with underweight using body weight, height and age. Methods: We used routinely collected laboratory parameters from a total of 4087 patients. The risk score was calculated on the basis of electrolytes, blood count, transaminases and LDH. The nine parameters used were summed as zlog-transformed values. Where appropriate, the scales were inverted so that high values represented higher risk. For statistical prediction of the risk score, weight/height and age reference values from the WHO, the CDC (Center of Disease Control) and representative studies of German children and adults (KIGGS and NNS) were used. Results: The score calculated from nine laboratory parameters already shows a convincing relationship with BMI. Among the weight measures used for height and age, the z-score from the CDC reference population emerged as the best estimate, explaining 34% of the variance in health risk measured by the laboratory score. The percentile rank for each age-specific median weight from the KIGGS/NNS still explained more than 31% of the variance. In contrast, percentiles explained less variance than BMI without age correction. Conclusions: The score we used from routine laboratory parameters appears to be an appropriate measure for assessing the health risk associated with underweight, as measured by the quality of the association with BMI. For estimating health risk based on weight, height and age alone, z-scores and percentages of age-specific median weight, as opposed to percentiles, are appropriate parameters. However, the study also shows that existing age-specific BMI reference values do not represent risk optimally. Improved statistical estimation methods would be desirable.
Interactive Associations between PPARγ and PPARGC1A and Bisphosphonate-Related Osteonecrosis of the Jaw in Patients with Osteoporosis
Authors: Kim Jung Sun , Kim Jin Woo , Yee Jeong , Kim Sun Jong , Chung Jee Eun , Gwak Hye Sun
Published: July 2023

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but severe adverse effect that can occur as a result of bisphosphonate treatment. This study aimed to examine the relationship between PPARγ and PPARGC1A polymorphisms and the BRONJ development in female osteoporosis patients undergoing bisphosphonate treatment. We prospectively conducted this nested case–control study at the Ewha Womans University Mokdong Hospital between 2014 and 2018. We assessed five single-nucleotide polymorphisms (SNPs) of PPARγ and six SNPs of PPARGC1A and performed a multivariable logistic regression analysis to determine the independent risk factors for developing BRONJ. There were a total of 123 patients included in this study and 56 patients (45.5%) developed BRONJ. In the univariate analysis, PPARGC1A rs2946385 and rs10020457 polymorphisms were significantly associated with BRONJ (p = 0.034, p = 0.020, respectively), although the results were not statistically significant in the multivariable analysis. Patients with the combined genotypes of GG in both PPARγ rs1151999 and PPARGC1A rs2946385 showed a 3.03-fold higher risk of BRONJ compared to individuals with other genotype combinations after adjusting for confounders (95% confidence interval (CI): 1.01–9.11). Old age (≥70 years) and duration of bisphosphonate use (≥60 months) increased the risk of BRONJ. The area under the receiver operating characteristic curve for the predicted probability was 0.78 (95% CI: 0.69–0.87, p < 0.001), demonstrating a satisfactory level of discriminatory power. Our study elucidated that PPARγ and PPARGC1A polymorphisms were interactively associated with BRONJ development. These results have potential implications for tailoring personalized treatments for females undergoing bisphosphonate therapy for osteoporosis.
Pomegranate: A Source of Multifunctional Bioactive Compounds Potentially Beneficial in Alzheimer’s Disease
Authors: Ciccone Lidia , Nencetti Susanna , Rossello Armando , Orlandini Elisabetta
Published: July 2023

Pomegranate fruit (PF) is a fruit rich in nutraceuticals. Nonedible parts of the fruit, especially peels, contain high amounts of bioactive components that have been largely used in traditional medicine, such as the Chinese, Unani, and Ayurvedic ones, for treating several diseases. Polyphenols such as anthocyanins, tannins, flavonoids, phenolic acids, and lignans are the major bioactive molecules present in PF. Therefore, PF is considered a source of natural multifunctional agents that exert simultaneously antioxidant, anti-inflammatory, antitumor, antidiabetic, cardiovascular, and neuroprotective activities. Recently, several studies have reported that the nutraceuticals contained in PF (seed, peel, and juice) have a potential beneficial role in Alzheimer’s disease (AD). Research suggests that the neuroprotective effect of PF is mostly due to its potent antioxidant and anti-inflammatory activities which contribute to attenuate the neuroinflammation associated with AD. Despite the numerous works conducted on PF, to date the mechanism by which PF acts in combatting AD is not completely known. Here, we summarize all the recent findings (in vitro and in vivo studies) related to the positive effects that PF and its bioactive components can have in the neurodegeneration processes occurring during AD. Moreover, considering the high biotransformation characteristics of the nutraceuticals present in PF, we propose to consider the chemical structure of its active metabolites as a source of inspiration to design new molecules with the same beneficial effects but less prone to be affected by the metabolic degradation process.
Probiotic Formulations Containing Fixed and Essential Oils Ameliorates SIBO-Induced Gut Dysbiosis in Rats
Authors: Aslan Ismail , Tarhan Celebi Leyla , Kayhan Hulya , Kizilay Emine , Gulbahar Mustafa Yavuz , Kurt Halil , Cakici Bekir
Published: July 2023

Dysbiosis of the gut microbiota is associated with the pathogenesis of intestinal diseases such as inflammatory bowel disease, irritable bowel syndrome (IBS), small intestinal bacterial overgrowth (SIBO), and metabolic disease states such as allergies, cardiovascular diseases, obesity, and diabetes. SIBO is a condition characterized by an increased number (>1 × 103 CFU) of abnormal bacterial species in the small intestine. Interest in SIBO has gained importance due to increased awareness of the human microbiome and its potential relationships with human health and disease, which has encouraged new work in this area. In recent years, standard antibiotic regimens (rifaximin and metronidazole) have been used to treat SIBO, but solo antibiotics or their derivatives are insufficient. In this study, the therapeutic effects of the probiotic form, which contains coconut oil and traces of peppermint-lemon-patchouli essential oil, were evaluated on the Dysbiosis-Based Rat SIBO Model. There are significant differences between sick and healthy rats (p = 0.014), between sick rats and rats treated with the oil mix plus probiotic mix protocol (p = 0.026), and between rats treated with only the probiotic and only oil protocols (p = 0.030) in the evaluation of TNF-α levels. Histologically, villi distortion and loss of crypts, epithelial shedding and necrotic changes in the apical regions of the villi, and inflammatory cell infiltrations extending to the lamina propria and submucosa were observed in sick rats. Mitotic figures in villus epithelium and crypts were observed in rats treated with 9.2 × 109 CFU/1000 mg/coconut oil + trace amounts of peppermint-lemon-patchouli essential oil and a probiotic mixture (oil + probiotic mix protocol). A regression of inflammatory reactions and an increase in goblet cells were observed. A decrease was observed in inflammation markers in sick rats. On the other hand, the oil plus probiotic mix protocol recovered digestive system defects in the animals caused by dysbiosis. In the future, these treatment approaches can be effective in the treatment of SIBO.
Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted-1,3,4-Oxadiazole Derivatives
Authors: Rana Sibghat Mansoor , Islam Muhammad , Saeed Hamid , Rafique Hummera , Majid Muhammad , Aqeel Muhammad Tahir , Imtiaz Fariha , Ashraf Zaman
Published: July 2023

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flurbiprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen –COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an –SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascertained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 µg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 µg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.
Global Research Trends and Hotspots Analysis of the Scientific Production of Amitriptyline: A Bibliometric Approach
Authors: Pereira Cristian dos Santos , Cruz Jorddy Neves , Ferreira Maria Karolina Martins , Baia-da-Silva Daiane Claydes , Fontes-Junior Eneas Andrade , Lima Rafael Rodrigues
Published: July 2023

Amitriptyline was first introduced as a medication to treat depression. Over time, this substance has been used to treat other conditions, such as gastrointestinal disorders, fibromyalgia, neuropathic pain, and analgesia, among others. However, there are no published studies that provide a broad view of the possible motivations that have led to changes in the use of amitriptyline. In this study, we have identified the landscape of use for amitriptyline based on knowledge mapping of the 100 most-cited articles about this drug. We searched Web of Science Core Collection without time and language restrictions. We obtained 14,446 results, but we only used the 100 most-cited articles that had amitriptyline as the object of study. We collected the following information from each article: authors, country of the corresponding authors, year of publication, citation count, citation density (number of citations per year), and keywords. In addition, we seek to map in the chosen articles study design and research findings. We found that since 1980, the use of amitriptyline has expanded beyond depression, moving to off-label use to treat a variety of diseases and conditions, including post-herpetic neuralgia, neuropathic pain, primary fibrosis, fibromyalgia, and migraine, can be considered a drug with more clinical applicability than its original clinical indication.
Delicate Hybrid Laponite–Cyclic Poly(ethylene glycol) Nanoparticles as a Potential Drug Delivery System
Authors: Tang Shengzhuang , Chen Jesse , Cannon Jayme , Chekuri Mona , Farazuddin Mohammad , Baker James R. , Wang Su He
Published: July 2023

The objective of the study was to explore the feasibility of a new drug delivery system using laponite (LAP) and cyclic poly(ethylene glycol) (cPEG). Variously shaped and flexible hybrid nanocrystals were made by both the covalent and physical attachment of chemically homogeneous cyclized PEG to laponite nanodisc plates. The size of the resulting, nearly spherical particles ranged from 1 to 1.5 µm, while PEGylation with linear methoxy poly (ethylene glycol) (mPEG) resulted in fragile sheets of different shapes and sizes. When infused with 10% doxorubicin (DOX), a drug commonly used in the treatment of various cancers, the LAP-cPEG/DOX formulation was transparent and maintained liquid-like homogeneity without delamination, and the drug loading efficiency of the LAP-cPEG nano system was found to be higher than that of the laponite-poly(ethylene glycol) LAP-mPEG system. Furthermore, the LAP-cPEG/DOX formulation showed relative stability in phosphate-buffered saline (PBS) with only 15% of the drug released. However, in the presence of human plasma, about 90% of the drug was released continuously over a period of 24 h for the LAP-cPEG/DOX, while the LAP-mPEG/DOX formulation released 90% of DOX in a 6 h burst. The results of the cell viability assay indicated that the LAP-cPEG/DOX formulation could effectively inhibit the proliferation of A549 lung carcinoma epithelial cells. With the DOX concentration in the range of 1–2 µM in the LAP-cPEG/DOX formulation, enhanced drug effects in both A549 lung carcinoma epithelial cells and primary lung epithelial cells were observed compared to LAP-mPEG/DOX. The unique properties and effects of cPEG nanoparticles provide a potentially better drug delivery system and generate interest for further targeting studies and applications.
Mechanistic Elucidation of Activation/Deactivation Signal Transduction within Neurotensin Receptor 1 Triggered by ‘Driver Chemical Groups’ of Modulators: A Comparative Molecular Dynamics Simulation
Authors: Lu Xun , Shi Xinchao , Fan Jigang , Li Mingyu , Zhang Yuxiang , Lu Shaoyong , Xu Guanghuan , Chen Ziqiang
Published: July 2023

Small-molecule modulators of neurotensin receptor 1 (NTSR1), a class A G-protein-coupled receptor (GPCR), has emerged as promising therapeutic agent for psychiatric disorders and cancer. Interestingly, a chemical group substitution in NTSR1 modulators can launch different types of downstream regulation, highlighting the significance of deciphering the internal fine-tuning mechanism. Here, we conducted a synergistic application of a Gaussian accelerated molecular dynamics simulation, a conventional molecular dynamics simulation, and Markov state models (MSM) to investigate the underlying mechanism of ‘driver chemical groups’ of modulators triggering inverse signaling. The results indicated that the flexibility of the leucine moiety in NTSR1 agonists contributes to the inward displacement of TM7 through a loosely coupled allosteric pathway, while the rigidity of the adamantane moiety in NTSR1 antagonists leads to unfavorable downward transduction of agonistic signaling. Furthermore, we found that R3226.54, Y3196.51, F3537.42, R1483.32, S3567.45, and S3577.46 may play a key role in inducing the activation of NTSR1. Together, our findings not only highlight the ingenious signal transduction within class A GPCRs but also lay a foundation for the development of targeted drugs harboring different regulatory functions of NTSR1.