bluuebunny/crossref_metadata_2025 huggingface dataset:
2′-Fucosyllactose Remits Colitis-Induced Liver Oxygen Stress through the Gut–Liver–Metabolites Axis
Authors: Yao Qianqian , Gao Yanan , Fan Linlin , Wang Jiaqi , Zheng Nan
Published: October 2022

Liver oxygen stress is one of the main extraintestinal manifestations of colitis and 5% of cases develop into a further liver injury and metabolic disease. 2′-fucosyllactose (2′-FL), a main member of human milk oligosaccharides (HMOs), has been found to exert efficient impacts on remitting colitis. However, whether 2′-FL exerts the function to alleviate colitis-induced liver injury and how 2′-FL influences the metabolism via regulating gut microbiota remain unknown. Herein, in our study, liver oxygen stress was measured by measuring liver weight and oxygen-stress-related indicators. Then, 16S full-length sequencing analysis and non-target metabolome in feces were performed to evaluate the overall responses of metabolites and intestinal bacteria after being treated with 2′-FL (400 mg/kg b.w.) in colitis mice. The results showed that, compared with the control group, the liver weight of colitis mice was significantly decreased by 18.30% (p < 0.05). After 2′-FL treatment, the liver weight was significantly increased by 12.65% compared with colitis mice (p < 0.05). Meanwhile, they exhibited higher levels of oxidation in liver tissue with decreasing total antioxidant capacity (T-AOC) (decreased by 17.15%) and glutathione (GSH) levels (dropped by 22.68%) and an increasing malondialdehyde (MDA) level (increased by 36.24%), and 2′-FL treatment could reverse those tendencies. Full-length 16S rRNA sequencing revealed that there were 39 species/genera differentially enriched in the control, dextran sulphate sodium (DSS), and DSS + 2′-FL groups. After treatment with 2′-FL, the intestinal metabolic patterns, especially glycometabolism and the lipid-metabolism-related process, in DSS mice were strikingly altered with 33 metabolites significantly down-regulated and 26 metabolites up-regulated. Further analysis found DSS induced a 40.01%, 41.12%, 43.81%, and 39.86% decline in acetic acid, propionic acid, butyric acid, and total short chain fatty acids (SCFAs) in colitis mice (all p < 0.05), respectively, while these were up-regulated to different degrees in the DSS + 2′-FL group. By co-analyzing the data of gut microbiota and metabolites, glycometabolism and lipid-metabolism-associated metabolites exhibited strong positive/negative relationships with Akkermansia_muciniphila (all p < 0.01) and Paraprevotella spp. (all p < 0.01), suggesting that the two species might play crucial roles in the process of 2′-FL alleviating colitis-induced liver oxygen stress. In conclusion, in the gut–liver–microbiotas axis, 2′-FL mediated in glucose and lipid-related metabolism and alleviated liver oxygen stress via regulating gut microbiota in the DSS-induced colitis model. The above results provide a new perspective to understand the probiotic function of 2′-FL.
Understanding and Use of Nutrition Labels of Prepackaged Food by University Students: A Cross-Sectional Study in Chongqing, China
Authors: Wei Hao , Jiang Ke , Liu Boya , Hu Zhichuan , Zhao Yong , Xu Hong , Sharma Manoj , Pu Chuan
Published: October 2022

Object: The correct use of nutrition labels for prepackaged food helps university students develop healthy eating habits and prevent the occurrence of chronic non-communicable diseases. This study evaluates the understanding and use of nutrition labels of prepackaged food by university students in four different fields of study in Chongqing, China. Methods: This cross-sectional study used an online survey platform conducted in July 2022 in colleges and universities in Chongqing, China. The convenience sampling method was used to select students in four different fields of study, including medicine, humanities, science and technology, and arts and sports. Ten questions were used to assess participants’ understanding of nutrition labels. A score of six or above (60%) indicates that the respondent has a basic understanding of the nutritional labels of prepackaged food. Descriptive statistics and generalized linear models (GLMs) were used to assess participants’ understanding and use of nutrition labels for prepackaged foods and their influencing factors. Results: A total of 1262 valid questionnaires was collected. The average age of the participants was 21.8 years (SD: 2.43), 50.1% were male, 80.8% were ethnic Han, and 50.9% were from rural areas. Only 21.3% of the university students in Chongqing had a good understanding of the nutrition labels of prepackaged food, where medical students were the highest (39.9%) and science and engineering students were the lowest (15.6%). Gender, ethnicity, grade, major, and whether received courses related to nutrition were influential factors in the understanding and use of nutrition labels of prepackaged food. Medical students also had more positive attitudes toward nutritional labels of prepackaged food. Conclusions: Understanding and use of nutrition labels for prepackaged food by university students in Chongqing are unsatisfactory. Student’s major was a significant influencing factor in nutrition label comprehension, with medical students having the greatest understanding. Based on these results, we suggest that nutrition and health courses should be popularized among non-medical students to narrow the differences between different fields of study. For university students in all fields of study, education and publicity of nutrition labels of prepackaged food are needed, not only in the classroom but also in daily life.
The Protective Effects of Corn Oligopeptides on Acute Alcoholic Liver Disease by Inhibiting the Activation of Kupffer Cells NF-κB/AMPK Signal Pathway
Authors: Wei Ying , Li Mingliang , Feng Zhiyuan , Zhang Di , Sun Meiling , Wang Yong , Chen Xiangning
Published: October 2022

Alcohol can cause injury and lead to an inflammatory response in the liver. The NF-κB/AMPK signaling pathway plays a vital role in regulating intracellular inflammatory cytokine levels. In this study, corn oligopeptides (CPs), as the research objects, were obtained from corn gluten meal, and their regulation of the activation of the Kupffer cell NF-κB/AMPK signal pathway induced by LPS was investigated. Results showed that ALT, AST, and inflammatory cytokines in mice serum after the administration of CPs at 0.2, 0.4, and 0.8 g/kg of body weight displayed a distinct (p < 0.05) reduction. On the other hand, the CPs also inhibited the expression of recognized receptor CD14 and TLR4, down-regulated P-JNK, P-ERK, and P-p-38, and thus inhibited inflammatory cytokine levels in Kupffer cells (KCs). Furthermore, four kinds of dipeptides with a leucine residue at the C-terminus that might exhibit down-regulated inflammatory cytokines in the NF-κB/AMPK signaling pathway functions were detected using HPLC-MS/MS. These results indicated that CPs have a potential application value in acute alcoholic liver disease.
Higher Total Cholesterol Concentration May Be Associated with Better Cognitive Performance among Elderly Females
Authors: Pang Ke , Liu Chunxia , Tong Jianbin , Ouyang Wen , Hu Shuntong , Tang Yongzhong
Published: October 2022

Background: The brain contains the highest level of cholesterol in the body, and the total amount of serum cholesterol in the blood has a huge impact on brain aging and cognitive performance. However, the association of total serum cholesterol with cognitive function remains uncertain. This study determines whether there is an association between the total amount of cholesterol in the blood and cognitive performance in elderly females without a history of stroke. Methods: This population-based cross-sectional study was conducted on elderly (over 60 years old) females and males without a history of stroke from 2011 to 2014 in the US National Health and Nutrition Examination Survey (NHANES). The primary exposure was total blood cholesterol, and the main outcome was cognitive performance; this association was assessed with logistic regression analysis and restricted cubic splines. Results: 1309 female and 1272 male participants were included. In females, higher total cholesterol was significantly associated with higher cognitive scores, particularly in the digit symbol substitution test (OR 0.51, 95% CI (0.36–0.72)) and the animal fluency test (OR 0.64, 95% CI (0.45–0.91)). This association remained significant in models adjusted for age, race, smoking status, education level, and chronic conditions (OR 0.40, 95% CI (0.25–0.63)). This association was not significant in males, however. Conclusions: A higher concentration of total cholesterol measured in later life may be a protective factor for cognitive performance among females over 60 years old without a history of stroke. Further, this association was more pronounced among women with higher levels of education than women with lower or no education.
Plant-Based Diets Improve Maternal–Fetal Outcomes in CKD Pregnancies
Authors: Attini Rossella , Leone Filomena , Chatrenet Antoine , Longhitano Elisa , Casula Viola , Tomasi Cont Alice , Zaccaria Gaia , Dalmasso Eleonora , Manzione Ana Maria , Masturzo Bianca , Torreggiani Massimo , Revelli Alberto , Cabiddu Gianfranca , Piccoli Giorgina Barbara
Published: October 2022

Reducing protein intake in patients with chronic kidney disease (CKD) limits glomerular stress induced by hyperfiltration and can prevent the progression of kidney disease; data in pregnancy are limited. The aim of this study is to analyze the results obtained in CKD patients who followed a plant-based moderately protein-restricted diet during pregnancy in comparison with a propensity-score-matched cohort of CKD pregnancies on unrestricted diets. A total of 52 CKD pregnancies followed up with a protein-restricted plant-based diet (Torino, Italy) were matched with a propensity score based on kidney function and proteinuria with CKD pregnancies with unrestricted protein intake (Cagliari Italy). Outcomes included preterm (<37 weeks) and very preterm (<34 weeks) delivery and giving birth to a small-for-gestational-age baby. The median age in our cohort was 34 years, 63.46% of women were primiparous, and the median body mass index (BMI) was 23.15 kg/m2 with 13.46% of obese subjects. No statistical differences were found between women on a plant-based diet and women who were not in terms of age, parity, BMI, obesity, CKD stage, timing of referral, or cause of CKD. No differences were found between the two groups regarding the week of delivery. However, the combined negative outcome (birth before 37 completed gestational weeks or birth-weight centile <10) occurred less frequently in women following the diet than in women in the control group (61.54% versus 80.77%; p = 0.03). The lower risk was confirmed in a multivariable analysis adjusted for renal function and proteinuria (OR: 0.260 [Q1:0.093–Q3:0.724]; p = 0.010), in which the increase in proteinuria from the first to the last check-up before delivery was lower in patients on plant-based diets (median from 0.80 to 1.87 g/24 h; p: ns) than in controls (0.63 to 2.39 g/24 h p < 0.0001). Plant-based, moderately protein-restricted diets in pregnancy in patients with CKD are associated with a lower risk of preterm delivery and small-for-gestational-age babies; the effect may be mediated by better stabilization of proteinuria.
Weizmannia coagulans BC2000 Plus Ellagic Acid Inhibits High-Fat-Induced Insulin Resistance by Remodeling the Gut Microbiota and Activating the Hepatic Autophagy Pathway in Mice
Authors: Jin Long , Dang Hongyang , Wu Jinyong , Yuan Lixia , Chen Xiangsong , Yao Jianming
Published: October 2022

(1) Background: Ellagic acid (EA) acts as a product of gut microbiota transformation to prevent insulin resistance, which is limited by high-fat diet (HFD)-induced dysbiosis. The aim of this study was to investigate the synergistic effects and mechanisms of supplementation with the probiotic Weizmannia coagulans (W. coagulans) on the prevention of insulin resistance by EA; (2) Methods: C57BL/6J mice were divided into five groups (n = 10/group): low-fat-diet group, high-fat-diet group, EA intervention group, EA + W. coagulans BC77 group, and EA + W. coagulans BC2000 group; (3) Result: W. coagulans BC2000 showed a synergistic effect on EA’s lowering insulin resistance index and inhibiting high-fat diet-induced endotoxemia. The combined effect of BC2000 and EA activated the autophagy pathway in the mouse liver, a urolithin-like effect. This was associated with altered β-diversity of gut microbiota and increased Eggerthellaceae, a potential EA-converting family. Ellagic acid treatment alone and the combined use of ellagic acid and W. coagulans BC77 failed to activate the hepatic autophagy pathway; (4) Conclusions: W. coagulans BC2000 can assist EA in its role of preventing insulin resistance. This study provides a basis for the development of EA-rich functional food supplemented with W. coagulans BC2000.
Nutritional Supplements and Lipedema: Scientific and Rational Use
Authors: Cannataro Roberto , Cione Erika
Published: October 2022

Lipedema is a pathology of the adipose tissue, in evident female prevalence, diagnosed clinically and still of not well-defined etiopathogenesis. Indeed, an estrogen-related component is present, and an inflammatory state and a condition of edema are present in most cases; even pain seems to be a recurring feature, and insulin resistance is also often associated with lipedema. The therapeutic approach is finally becoming holistic. Therefore, with surgery, physiotherapy, and elastic compression therapy, the nutritional aspect of food supplementation is gaining much value. The objective of the present work is to consider the nutritional supplements that could be useful to manage this condition, underlining that, at the moment, the specific literature is practically non-existent. The most promising supplements seem to be omega 3 fish oil, polyphenols, and vitamin C, but the need for studies in this sector is urgent.
One-Year Surveillance of SARS-CoV-2 Virus in Natural and Drinking Water
Authors: Salvador Daniel , Caeiro Maria Filomena , Neto Célia , Carneiro Rui Neves
Published: October 2022

Although the SARS-CoV-2 virus has been detected in wastewater from several countries, monitoring its presence in other water matrices is still limited. This study aimed to evaluate the presence of this virus in natural and drinking water over one year of monitoring (2021). A survey of viral RNA was carried out by RT-qPCR in concentrated samples of surface water, groundwater, and drinking water from different regions of Portugal. SARS-CoV-2 RNA—quantified in genomic copies per liter (gc/L) of sampled water—was not detected in groundwater, but was detected and quantified in samples of surface water (two out of 43; 8035 and 23,757 gc/L) and in drinking water (one out of 43 samples; 7463 gc/L). The study also detected and quantified Norovirus RNA, intending to confirm the use of this enteric virus to assess variations in fecal matter throughout the sampling campaign. The samples positive for SARS-CoV-2 RNA also had the highest concentrations of Norovirus RNA—including the drinking water sample, which proved negative for fecal enteric bacteria (FIB). These results indicate that, to protect human health, it is advisable to continue monitoring these viruses, and noroviruses as fecal indicators (FI) as well—especially in low-flow water bodies that receive wastewater.
Characterisation of the Theileria orientalis Piroplasm Proteome across Three Common Genotypes
Authors: Jenkins Cheryl , Micallef Melinda L. , Padula Matthew P. , Bogema Daniel R.
Published: October 2022

Theileria orientalis is an emerging apicomplexan pathogen of cattle occurring in areas populated by the principal vector tick, Haemaphysalis longicornis. Unlike transforming Theileria spp. that induce cancer-like proliferation of lymphocytes via their schizont stage, T. orientalis destroys host erythrocytes during its piroplasm phase resulting in anaemia. The underlying pathogenic processes of T. orientalis infection are poorly understood; consequently, there are no vaccines for prevention of T. orientalis infection and chemotherapeutic options are limited. To identify antigens expressed during the piroplasm phase of T. orientalis, including those which may be useful targets for future therapeutic development, we examined the proteome across three common genotypes of the parasite (Ikeda, Chitose and Buffeli) using preparations of piroplasms purified from bovine blood. A combination of Triton X-114 extraction, one-dimensional electrophoresis and LC-MS/MS identified a total of 1113 proteins across all genotypes, with less than 3% of these representing host-derived proteins. Just over three quarters of T. orientalis proteins (78%) identified were from the aqueous phase of the TX-114 extraction representing cytosolic proteins, with the remaining 22% from the detergent phase, representing membrane-associated proteins. All enzymes involved in glycolysis were expressed, suggesting that this is the major metabolic pathway used during the T. orientalis piroplasm phase. Proteins involved in binding and breakdown of haemoglobin were also identified, suggesting that T. orientalis uses haemoglobin as a source of amino acids. A number of proteins involved in host cell interaction were also identified which may be suitable targets for the development of chemotherapeutics or vaccines.
Parasitemia and Differential Tissue Tropism in Mice Infected with Trypanosoma cruzi Isolates Obtained from Meccus phyllosoma in the State of Oaxaca, Mexico
Authors: Flores-Villegas Any Laura , Jiménez-Cortés Jesús Guillermo , González James , Moreno-Rodríguez Adriana , Pérez-Cabeza de Vaca Rebeca , Segal-Kischinevzky Claudia , Bucio-Torres Martha I. , De Fuentes-Vicente José A. , Nava-Lazaro Elisabeth , Salazar-Schettino Paz María , Cabrera Bravo Margarita
Published: October 2022

Trypanosoma cruzi is a parasite transmitted by the feces of triatomines. Many triatomine species are found in Mexico, and various T. cruzi variants have been isolated from these species, each showing very different virulence and cell tropism. The isolates were obtained from Meccus phyllosoma specimens in three localities in the state of Oaxaca, Mexico: Tehuantitla, Vixhana, and Guichivere. The virulence of each isolate was assessed by quantifying parasitemia, survival, and histopathologic findings. The lineage of each isolate was identified using the mini-exon gene. The expression of the tssa gene during infection was detected in the heart, esophagus, gastrocnemius, and brain. Our results show that the maximum post-infection parasitemia was higher for the Tehuantitla isolate. On genotyping, all isolates were identified as T. cruzi I. The amastigotes in the heart and gastrocnemius were verified for all isolates, but in the brain only for Tehuantitla and Vixhana. The tssa expression allowed us to detect T. cruzi isolates, for Tehuantitla, predominantly in the heart. For Vixhana, a higher tssa expression was detected in gastrocnemius, and for Guichivere, it was higher in the esophagus. Results show that virulence, tropism, and tssa expression can vary, even when the isolates are derived from the same vector species, in the same region, and at similar altitudes.
Toxoplasmosis in Captive Ring-Tailed Lemurs (Lemur catta)
Authors: Rocchigiani Guido , Fonti Niccolò , Nardoni Simona , Cavicchio Paolo , Mancianti Francesca , Poli Alessandro
Published: October 2022

Toxoplasma gondii is one of the most common protozoan parasites and is widely present in all warm-blooded animals. Although clinical disease is uncommon, some species, including ring-tailed lemurs (Lemur catta), have been found to develop acute and lethal toxoplasmosis. The aim of this study was to describe the pathologic, immunohistochemical, serological, and molecular findings of an outbreak of fatal toxoplasmosis in three captive ring-tailed lemurs in Central Italy in 2009. The animals died acutely within few days. The necropsy was immediately performed; necrotic lesions in the spleen, liver, and kidney, as well as interstitial pneumonia, were found histologically. All animals had high titers of anti–T. gondii-specific antibodies (1:1280 IgM and 1:640 IgG) according to a modified agglutination test (MAT) and immunohistochemistry showed scattered tachyzoites in the target organs. Diagnosis was confirmed by PCR and clonal type II was identified. In addition, the seven co-habiting lemurs were seronegative. This paper reports the first outbreak of acute disseminated toxoplasmosis in captive ring-tailed lemurs in Italy. These findings confirm the high susceptibility of this endangered species to toxoplasma infection, which may be considered a further threat to captive population viability.
Outcomes of Patients Receiving a Kidney Transplant or Remaining on the Transplant Waiting List at the Epicentre of the COVID-19 Pandemic in Europe: An Observational Comparative Study
Authors: Perego Marta , Iesari Samuele , Gandolfo Maria Teresa , Alfieri Carlo , Delbue Serena , Cacciola Roberto , Ferraresso Mariano , Favi Evaldo
Published: October 2022

Since the declaration of the COVID-19 pandemic, the number of kidney transplants (KT) performed worldwide has plummeted. Besides the generalised healthcare crisis, this unprecedented drop has multiple explanations such as the risk of viral transmission through the allograft, the perceived increase in SARS-CoV-2-related morbidity and mortality in immunocompromised hosts, and the virtual “safety” of dialysis while awaiting effective antiviral prophylaxis or treatment. Our institution, operating at the epicentre of the COVID-19 pandemic in Italy, has continued the KT programme without pre-set limitations. In this single-centre retrospective observational study with one-year follow-up, we assessed the outcomes of patients who had undergone KT (KTR) or remained on the transplant waiting list (TWL), before (Pre-COV) or during (COV) the pandemic. The main demographic and clinical characteristics of the patients on the TWL or receiving a KT were very similar in the two periods. The pandemic did not affect post-transplant recipient and allograft loss rates. On the contrary, there was a trend toward higher mortality among COV-TWL patients compared to Pre-COV-TWL subjects. Such a discrepancy was primarily due to SARS-CoV-2 infections. Chronic exposure to immunosuppression, incidence of delayed allograft function, and rejection rates were comparable. However, after one year, COV-KTR showed significantly higher median serum creatinine than Pre-COV-KTR. Our data confirm that KT practice could be safely maintained during the COVID-19 pandemic, with excellent patient- and allograft-related outcomes. Strict infection control strategies, aggressive follow-up monitoring, and preservation of dedicated personnel and resources are key factors for the optimisation of the results in case of future pandemics.
Alterations in Genes rib, scpB and Pilus Island Decrease the Prevalence of Predominant Serotype V, Not III and VI, of Streptococcus agalactiae from 2008 to 2012
Authors: Tsai I-An , Su Yaochi , Wang Ying-Hsiang , Chu Chishih
Published: October 2022

Streptococcus agalactiae (GBS) can infect newborns, pregnant women and immunocompromised or elderly people. This study aimed to investigate differences in three pilus genes and virulence genes pavA, cfb, rib and scpB and changes in predominant serotypes III, V and VI from 2008 to 2012. The susceptibilities to penicillin, ceftriaxone, azithromycin, erythromycin, clindamycin, levofloxacin and moxifloxacin of 145 GBS strains of serotype III, V and VI strains from 2008 and 2012 were determined using disc diffusion method. PCR identification of ST-17, the pilus genes and virulence genes; multilocus sequence typing (MLST); and conserved domain and phylogenetic analysis of scpB-1 and scpB-2 proteins were performed. A dramatic number reduction was observed in serotype V, not III and V, from 2008 to 2012. The rate of resistance to azithromycin, clindamycin and erythromycin was the highest in serotype V. ST-17 was only found in serotype III with pilus genes PI-1+PI-2b. The major pilus genotype was PI-1+PI-2a. Serotype V without the rib gene was reduced in number between two studied years. Compared to scpB-1, scpB-2 had a 128-bp deletion in a PA C5a-like peptidase domain and putative integrin-binding motif RGD. In conclusion, reduction in serotype V may be due to presence of scpB-2 or lack of genes scpB and rib.
Engineered Oncolytic Adenoviruses: An Emerging Approach for Cancer Therapy
Authors: Tan Ee Wern , Abd-Aziz Noraini , Poh Chit Laa , Tan Kuan Onn
Published: October 2022

Cancer is among the major leading causes of mortality globally, and chemotherapy is currently one of the most effective cancer therapies. Unfortunately, chemotherapy is invariably accompanied by dose-dependent cytotoxic side effects. Recently, genetically engineered adenoviruses emerged as an alternative gene therapy approach targeting cancers. This review focuses on the characteristics of genetically modified adenovirus and oncology clinical studies using adenovirus-mediated gene therapy strategies. In addition, modulation of the tumor biology and the tumor microenvironment as well as the immunological responses associated with adenovirus-mediate cancer therapy are discussed.
Making a Comeback: Syphilitic Hepatitis in a Patient with Late Latent Syphilis—Case Report and Review of the Literature
Authors: Plesa Alina , Gheorghe Liliana , Hincu Corina Elena , Clim Andreea , Nemteanu Roxana
Published: October 2022

Treponema pallidum infection has emerged in recent years as an important community threat and burden to the health care system. Here, we report the case of a patient with cholestatic liver disease secondary to late latent syphilis. A 41 year-old male patient was referred to the clinic for assessment of an abnormal liver function panel. Ultrasound of the abdomen demonstrated an intense liver echogenicity, normal bile ducts, and no ascites. Virologic study revealed negative results for antibodies against common viral hepatitis and metabolic and autoimmune disease. The patient was tested for syphilis and a positive result was reported. The patient was diagnosed with late latent syphilis and syphilitic hepatitis and initiated benzathine penicillin at G 7.2 million units total, delivered as three doses of 2.4 million units intramuscular each at one-week intervals. He was assessed monthly and by the end of the sixth month, he had nonreactive VDRL (seroconversion), which confirmed recovery. Syphilitic hepatitis is an overlooked type of hepatitis and should be kept in mind as a differential diagnosis in an abnormal liver panel of uncertain etiology. Health care providers should be advised that higher levels of ALP may be the single landmark in cases of syphilitic hepatitis.
Frequency of Detection of Respiratory Pathogens in Clinically Healthy Show Horses Following a Multi-County Outbreak of Equine Herpesvirus-1 Myeloencephalopathy in California
Authors: Wilcox Abigail , Barnum Samantha , Wademan Cara , Corbin Rachel , Escobar Edlin , Hodzic Emir , Schumacher Stephen , Pusterla Nicola
Published: October 2022

Actively shedding healthy horses have been indicated as a possible source of respiratory pathogen outbreak, transmission, and spread. Using nasal swabs from clinically healthy sport horses submitted for qPCR testing after an outbreak of equine herpesvirus-1 (EHV-1) myeloencephalopathy (EHM) in the spring of 2022, this study aimed to identify the rate of clinically healthy horses shedding common and less characterized respiratory pathogens within the sport horse population to better understand their role in outbreaks. Swabs were collected during a required quarantine and testing period, according to the United States Equestrian Federation (USEF), and showed return-to-competition requirements. Common respiratory pathogens, such as equine influenza virus (EIV), EHV-4, and equine rhinitis B virus (ERBV), were found at low but stable frequencies within previously reported ranges, whereas EHV-1 and Streptococcus equi subspecies equi (S. equi) were found at or above previously reported frequencies. Less characterized respiratory pathogens, such as EHV-2, EHV-5, and S. equi subspecies zooepidemicus (S. zooepidemicus), were found within previously reported ranges. Common respiratory pathogens, especially EHV-1 following the multiple EHM outbreaks, were found to be circulating in clinically healthy sport horse populations, reflecting their silent transmission. The strategy of quarantine and EHV-1 qPCR testing of clinically healthy horses was successful at eliminating additional EHM outbreaks and facilitating safe return to competition with no reported respiratory disease outbreaks following the subsequent shows in California.
A New Role for Old Friends: Effects of Helminth Infections on Vaccine Efficacy
Authors: Zhu Feifan , Liu Wenyi , Liu Tong , Shi Linpeng , Zheng Wenwen , Guan Fei , Lei Jiahui
Published: October 2022

Vaccines are one of the most successful medical inventions to enable the eradication or control of common and fatal diseases. Environmental exposure of hosts, including helminth infections, plays an important role in immune responses to vaccines. Given that helminth infections are among the most common infectious diseases in the world, evaluating vaccine efficiency in helminth-infected populations may provide critical information for selecting optimal vaccination programs. Here, we reviewed the effects of helminth infections on vaccination and its underlying immunological mechanisms, based on findings from human studies and animal models. Moreover, the potential influence of helminth infections on SARS-CoV-2 vaccine was also discussed. Based on these findings, there is an urgent need for anthelmintic treatments to eliminate helminth suppressive impacts on vaccination effectiveness during implementing mass vaccination in parasite endemic areas.
Comparison of the Efficacy of Intramammary or Injectable Antibiotic Administration against Staphylococcal Mastitis in Ewes
Authors: Vasileiou Natalia G. C. , Fthenakis George C. , Mavrogianni Vasia S.
Published: October 2022

The objectives of the work were (a) to compare the efficacy of two routes for antibiotic administration in the treatment of mastitis in ewes and (b) to assess the potential importance of the timing of the initiation of the therapeutic regime on the outcome of the treatment. The ewes were allocated at random into three equal groups; intramammary inoculation with a Staphylococcus simulans isolate was performed, and clinical mastitis developed. The ewes in groups T1 (n = 6) and T2 (n = 6) were treated by the intramammary administration of ampicillin and dicloxacillin (two administrations with a 12-h interval). The ewes in group T3 (n = 6) were treated by the intramuscular injection of ampicillin and dicloxacillin (0.75 mL per 10 kg bodyweight, three injections with a 24-h interval). In the ewes in groups T1 and T3, treatment started immediately when the clinical signs of mastitis were first detected during the periodic examination of the ewes; in the ewes in group T2, treatment started 24 h after the clinical signs of mastitis were first detected. The animals were monitored clinically; mammary secretion samples were collected for bacteriological and cytological examinations. The median duration of the clinical signs was 4.75, 7.13, and 4.75 d for T1, T2, and T3; significant differences in clinical severity between the groups were seen until the 7th day post-treatment. The median duration of bacterial recovery was 3.25, 8.00, and 8.00 d for T1, T2, and T3; significant differences in the frequency of bacterial recovery between the groups were seen until (64.1%, 94.9%, and 96.2% of the samples) and after (2.9%, 16.7%, and 11.8%) the 7th day post-treatment. The median period required for the complete cure (clinical, bacteriological, and cytological) was shorter in the T1 than in the T2 and T3 ewe groups: 20.0, 32.0, and 24.5 d, respectively. The findings cover a gap in the available literature regarding the treatment of clinical mastitis in ewes. Early treatment resulted in the improved cure of the infection. The comparison of the intramammary and injectable routes for antibiotic administration indicated some benefit for the former, primarily in the post-treatment somatic cell counts.
Fungal Rhinosinusitis Caused by a Curvularia sp. Infection in a Female Sumatran Orangutan: A Case Report
Authors: Uwiera Richard R. E. , Vijayasekaran Shyan , Wallace Alisa M. , Reese David J. , Walsh Audra L. , Uwiera Trina C. , Vaughan-Higgins Rebecca , Vitali Simone D.
Published: October 2022

Mycotic nasal cavity and paranasal sinus infections in non-human primates (NHPs) are relatively uncommon diseases of the upper respiratory tract. This case study describes the clinical and pathological features as well as the diagnostic techniques and interventions applied to treat the associated disease. A 23-year-old primiparous female Sumatran orangutan residing at Perth Zoo in Western Australia developed intermittent episodes of right-sided epistaxis. An ulcerative nasal mass was identified from a diagnostic endoscopy. The mass was initially biopsied and showed the morphological characteristics of a dematiaceous fungal organism upon a histological examination. There were prominent mucosal and submucosal granulomatous infiltrates containing histocytes, giant cells, and lymphocytes admixed with fewer numbers of neutrophils and eosinophils surrounding the fungal organism. The organism was identified as Curvularia sp. by the fungal characteristics associated with the histopathology, culture growth, and PCR analysis. The mass was subsequently removed with endoscopic sinus surgery (ESS) and the orangutan was medically treated with itraconazole for several months. The recovery was uneventful and the orangutan returned to full health.
Synthesis, Biological Evaluation and Machine Learning Prediction Model for Fluorinated Cinchona Alkaloid-Based Derivatives as Cholinesterase Inhibitors
Authors: Ramić Alma , Matošević Ana , Debanić Barbara , Mikelić Ana , Primožič Ines , Bosak Anita , Hrenar Tomica
Published: October 2022

A series of 46 Cinchona alkaloid derivatives that differ in positions of fluorine atom(s) in the molecule were synthesized and tested as human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. All tested compounds reversibly inhibited AChE and BChE in the nanomolar to micromolar range; for AChE, the determined enzyme-inhibitor dissociation constants (Ki) ranged from 3.9–80 µM, and 0.075–19 µM for BChE. The most potent AChE inhibitor was N-(para-fluorobenzyl)cinchoninium bromide, while N-(meta-fluorobenzyl)cinchonidinium bromide was the most potent BChE inhibitor with Ki constant in the nanomolar range. Generally, compounds were non-selective or BChE selective cholinesterase inhibitors, where N-(meta-fluorobenzyl)cinchonidinium bromide was the most selective showing 533 times higher preference for BChE. In silico study revealed that twenty-six compounds should be able to cross the blood-brain barrier by passive transport. An extensive machine learning procedure was utilized for the creation of multivariate linear regression models of AChE and BChE inhibition. The best possible models with predicted R2 (CD-derivatives) of 0.9932 and R2(CN-derivatives) of 0.9879 were calculated and cross-validated. From these data, a smart guided search for new potential leads can be performed. These results pointed out that quaternary Cinchona alkaloids are the promising structural base for further development as selective BChE inhibitors which can be used in the central nervous system.
Immunostimulatory Effect of Postbiotics Prepared from Phellinus linteus Mycelial Submerged Culture via Activation of Spleen and Peyer’s Patch in C3H/HeN Mice
Authors: Suh Min Geun , Shin Hyun Young , Jeong Eun-Jin , Kim Gaeuleh , Jeong Se Bin , Ha Eun Ji , Choi Sang-Yong , Moon Sung-Kwon , Yu Kwang-Won , Suh Hyung-Joo , Kim Hoon
Published: October 2022

Medicinal mushrooms are an important natural resource promoting health benefits. Herein, Phellinus linteus mycelia were prepared under submerged cultivation, the mycelium-containing culture broth was extracted as a whole to obtain the postbiotic materials (PLME), and its effect on the immune system was evaluated in normal C3H/HeN mice. Oral administration of PLME for 4 weeks was well tolerated and safe. In the PLME-administered groups, in addition to the production of immunostimulatory cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), the mitogenic activity was significantly increased. PLME administration also significantly increased the levels of serum immunoglobulin G (IgG) and IgA in the small intestinal fluid and Peyer’s patches and enhanced Peyer’s patch-mediated bone marrow cell proliferation activity and cytokine production (IL-2, IL-6, and IFN-γ). Histomorphometric analyses showed an increase in immune cells in the spleen and small intestinal tissues of mice administered PLME, supporting the rationale for its immune system activation. PLME mainly contained neutral sugar (969.1 mg/g), comprising primarily of glucose as a monosaccharide unit. The β-glucan content was 88.5 mg/g. Data suggest that PLME effectively promote immune function by stimulating the systemic immune system through the spleen and intestinal immune tissues. PLME can thus be developed as a functional ingredient to enhance immune functions.
Phytochemical Profiling, Antioxidant, Antimicrobial and Cholinesterase Inhibitory Effects of Essential Oils Isolated from the Leaves of Artemisia scoparia and Artemisia absinthium
Authors: Khan Farman Ali , Khan Nasir Mehmood , Ahmad Shujaat , Nasruddin  , Aziz Riffat , Ullah Ihsan , Almehmadi Mazen , Allahyani Mamdouh , Alsaiari Ahad Amer , Aljuaid Abdulelah
Published: October 2022

The current studies were focused on the phytochemical profiling of two local wild Artemisia species, Artemisia scoparia and Artemisia absinthium leaves’ essential oils, extracted via the hydro distillation method along with evaluation of their antioxidant as well as antimicrobial effects. The constituents of EOs were identified using a combined gas chromatography-mass spectrometric (GC-MS) technique. A total of 25 compounds in A. scoparia essential oil (EOAS) were identified, and 14 compounds with percentage abundance of >1% were tabulated, the major being tocopherol derivatives (47.55%). A total of nine compounds in Artemisia absinthium essential oil (EOAA) were enlisted (% age > 1%), the majority being oleic acid derivatives (41.45%). Strong antioxidant effects were pronounced by the EOAS in DPPH (IC50 = 285 ± 0.82 µg/mL) and in ABTS (IC50 = 295 ± 0.32 µg/mL) free radical scavenging assays. Both the EOs remained potent in inhibiting the growth of bacterial species; Escherichia coli (55–70%) and Shigella flexneri (60–75%) however remained moderately effective against Bacillus subtilis as well as Staphylococcus aureus. Both EOAS and EOAA strongly inhibited the growth of the tested fungal species, especially Aspergillus species (up to 70%). The oils showed anti-cholinesterase potential by inhibiting both Acetylcholinesterase (AChE; IC50 = 30 ± 0.04 µg/mL (EOAS), 32 ± 0.05 µg/mL (EOAA) and Butyrylcholinesterase (BChE; IC50 = 34 ± 0.07 µg/mL (EOAS), 36 ± 0.03 µg/mL (EOAA). In conclusion, the essential oils of A. scoparia and A. absinthium are promising antioxidant, antimicrobial and anticholinergic agents with a different phytochemical composition herein reported for the first time.
Effects of Myristicin in Association with Chemotherapies on the Reversal of the Multidrug Resistance (MDR) Mechanism in Cancer
Authors: Seneme Elisa Frederico , dos Santos Daiane Carla , de Lima Carolina Afonso , Zelioli Ícaro Augusto Maccari , Sciani Juliana Mozer , Longato Giovanna Barbarini
Published: October 2022

A range of drugs used in cancer treatment comes from natural sources. However, chemotherapy has been facing a major challenge related to multidrug resistance (MDR), a mechanism that results in a decrease in the intracellular concentration of chemotherapeutic agents, resulting in reduced treatment efficacy. The protein most frequently related to this effect is P-glycoprotein (P-gp), which is responsible for promoting drug efflux into the extracellular environment. Myristicin is a natural compound isolated from nutmeg and has antiproliferative activity, which has been reported in the literature. The present study aimed to evaluate the effect of the association between myristicin and chemotherapeutic agents on the NCI/ADR-RES ovarian tumor lineage that presents a phenotype of multidrug resistance by overexpression of P-gp. It was observed that myristicin showed no cytotoxic activity for this cell line, since its IC50 was >1 mM. When myristicin was associated with the chemotherapeutic agents cisplatin and docetaxel, it potentiated their cytotoxic effects, a result evidenced by the decrease in their IC50 of 32.88% and 75.46%, respectively. Studies conducted in silico indicated that myristicin is able to bind and block the main protein responsible for MDR, P-glycoprotein. In addition, the molecule fits five of the pharmacokinetic parameters established by Lipinski, indicating good membrane permeability and bioavailability. Our hypothesis is that, by blocking the extrusion of chemotherapeutic agents, it allows these agents to freely enter cells and perform their functions, stopping the cell cycle. Considering the great impasse in the chemotherapeutic treatment of cancer that is the MDR acquired by tumor cells, investigating effective targets to circumvent this resistance remains a major challenge that needs to be addressed. Therefore, this study encourages further investigation of myristicin as a potential reverser of MDR.
Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review
Authors: Bouyahya Abdelhakim , El Omari Nasreddine , Bakha Mohamed , Aanniz Tarik , El Menyiy Naoual , El Hachlafi Naoufal , El Baaboua Aicha , El-Shazly Mohamed , Alshahrani Mohammed Merae , Al Awadh Ahmed Abdullah , Lee Learn-Han , Benali Taoufiq , Mubarak Mohammad S.
Published: October 2022

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.
The IQA Energy Partition in a Drug Design Setting: A Hepatitis C Virus RNA-Dependent RNA Polymerase (NS5B) Case Study
Authors: Zapata-Acevedo César A. , Popelier Paul L. A.
Published: October 2022

The interaction of the thumb site II of the NS5B protein of hepatitis C virus and a pair of drug candidates was studied using a topological energy decomposition method called interacting quantum atoms (IQA). The atomic energies were then processed by the relative energy gradient (REG) method, which extracts chemical insight by computation based on minimal assumptions. REG reveals the most important IQA energy contributions, by atom and energy type (electrostatics, sterics, and exchange–correlation), that are responsible for the behaviour of the whole system, systematically from a short-range ligand–pocket interaction until a distance of approximately 22 Å. The degree of covalency in various key interatomic interactions can be quantified. No exchange–correlation contribution is responsible for the changes in the energy profile of both pocket–ligand systems investigated in the ligand–pocket distances equal to or greater than that of the global minimum. Regarding the hydrogen bonds in the system, a “neighbour effect” was observed thanks to the REG method, which states that a carbon atom would rather not have its covalent neighbour oxygen form a hydrogen bond. The combination of IQA and REG enables the automatic identification of the pharmacophore in the ligands. The coarser Interacting Quantum Fragments (IQF) enables the determination of which amino acids of the pocket contribute most to the binding and the type of energy of said binding. This work is an example of the contribution topological energy decomposition methods can make to fragment-based drug design.
The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models
Authors: Mitkin Nikita A. , Pavshintcev Vsevolod V. , Sukhanova Iuliia A. , Doronin Igor I. , Babkin Gennady A. , Sadagurski Marianna , Malyshev Anton V.
Published: October 2022

The aim of this study was to develop a novel peptide potentially applicable for the treatment of metabolic conditions, such as obesity and type 2 diabetes (T2D). We identified CHM-273S from the list of peptides from milk hydrolysate obtained by HPLC/MS-MS. In vitro analysis of primary murine fibroblasts indicated the potential of CHM-273S to upregulate IRS2 mRNA expression. CHM-273S showed a prominent anorexigenic effect in mice with the induction of a key mechanism of leptin signaling via STAT3 in the hypothalamus as a possible effector. In the animal model of metabolic disease, CHM-273S alleviated glucose intolerance and insulin resistance, and induced phosphorylation of Akt at Ser473 and Thr308 in the hepatocytes of high-sucrose diet-fed rats. In a murine model of T2D, CHM-273S mitigated high-fat diet-induced hyperglycemia and insulin resistance and improved low-grade inflammation by diminishing serum TNFα. Mice treated with chronic CHM-273S had a significant reduction in body weight, with a lower visceral fat pad weight and narrow adipocytes. The effects of the peptide administration were comparable to those of metformin. We show the potential of CHM-273S to alleviate diet-induced metabolic alterations in rodents, substantiating its further development as a therapeutic for obesity, T2D, and other metabolic conditions.