bluuebunny/crossref_metadata_2025 huggingface dataset:
A numerical population density technique for N-dimensional neuron models
Authors: Osborne Hugh , de Kamps Marc
Published: July 2022

Population density techniques can be used to simulate the behavior of a population of neurons which adhere to a common underlying neuron model. They have previously been used for analyzing models of orientation tuning and decision making tasks. They produce a fully deterministic solution to neural simulations which often involve a non-deterministic or noise component. Until now, numerical population density techniques have been limited to only one- and two-dimensional models. For the first time, we demonstrate a method to take an N-dimensional underlying neuron model and simulate the behavior of a population. The technique enables so-called graceful degradation of the dynamics allowing a balance between accuracy and simulation speed while maintaining important behavioral features such as rate curves and bifurcations. It is an extension of the numerical population density technique implemented in the MIIND software framework that simulates networks of populations of neurons. Here, we describe the extension to N dimensions and simulate populations of leaky integrate-and-fire neurons with excitatory and inhibitory synaptic conductances then demonstrate the effect of degrading the accuracy on the solution. We also simulate two separate populations in an E-I configuration to demonstrate the technique's ability to capture complex behaviors of interacting populations. Finally, we simulate a population of four-dimensional Hodgkin-Huxley neurons under the influence of noise. Though the MIIND software has been used only for neural modeling up to this point, the technique can be used to simulate the behavior of a population of agents adhering to any system of ordinary differential equations under the influence of shot noise. MIIND has been modified to render a visualization of any three of an N-dimensional state space of a population which encourages fast model prototyping and debugging and could prove a useful educational tool for understanding dynamical systems.
Coordinate-based (ALE) meta-analysis of acupuncture for musculoskeletal pain
Authors: Ha Guodong , Tian Zilei , Chen Jiyao , Wang Shuo , Luo Aga , Liu Yunyu , Tang Juan , Lai Ningyuan , Zeng Fang , Lan Lei
Published: July 2022

Background

Neuroimaging studies have been widely used to investigate brain regions' alterations in musculoskeletal pain patients. However, inconsistent results have hindered our understanding of the central modulatory effects of acupuncture for musculoskeletal pain. The main objective of our investigation has been to obtain comprehensive evidence of acupuncture for musculoskeletal pain diseases.

Methods

The PubMed, Web of Science, Google Scholar, Embase, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine disc Database, Clinical Trial Registration Platform, and Wanfang Database were searched for neuroimaging studies on musculoskeletal pain diseases published from inception up to November 2021. Then, the relevant literature was screened to extract the coordinates that meet the criteria. Finally, the coordinate-based meta-analysis was performed using the activation likelihood estimation algorithm.

Results

A total of 15 neuroimaging studies with 183 foci of activation were included in this study. The ALE meta-analysis revealed activated clusters in multiple cortical and sub-cortical brain structures in response to acupuncture across studies, including the thalamus, insula, caudate, claustrum, and lentiform nucleus.

Conclusions

The studies showed that acupuncture could modulate different brain regions, including the thalamus, insula, caudate, claustrum, and lentiform nucleus. The findings offer several insights into the potential mechanisms of acupuncture for musculoskeletal pain and provide a possible explanation for the observed clinical benefit of this therapy.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227850, identifier: CRD42021227850.
Structural Connectivity in Down Syndrome and Alzheimer’s Disease
Authors: Saini Fedal , Dell’Acqua Flavio , Strydom Andre
Published: July 2022

Down syndrome (DS) arises from the triplication of chromosome 21, which leads to an atypical neurodevelopment and the overproduction of the amyloid precursor protein, predisposing to early Alzheimer’s disease (AD). Not surprisingly, trisomy 21 is widely considered a model to study predementia stages of AD. After decades, in which neural loss was the main focus, research in AD is now moving toward understanding the neurodegenerative aspects affecting white matter. Motivated by the development of magnetic resonance imaging (MRI)-based diffusion techniques, this shift in focus has led to several exploratory studies on both young and older individuals with DS. In this review, we synthesise the initial efforts made by researchers in characterising in-vivo structural connectivity in DS, together with the AD footprint on top of such pre-existing connectivity related to atypical brain development. The white matter structures found to be affected in DS are the corpus callosum and all the main long-association fibres, namely the inferior fronto-occipital fasciculus, the inferior and superior longitudinal fasciculus, the uncinate fasciculus and the cingulum bundle. Furthermore, the cingulum bundle and the corpus callosum appear to be particularly sensitive to early AD changes in this population. Findings are discussed in terms of their functional significance, alongside methodological considerations and implications for future research.
Potential Diagnostic Applications of Multi-Delay Arterial Spin Labeling in Early Alzheimer’s Disease: The Chinese Imaging, Biomarkers, and Lifestyle Study
Authors: Sun Mengfan , Wang Yan-Li , Li Runzhi , Jiang Jiwei , Zhang Yanling , Li Wenyi , Zhang Yuan , Jia Ziyan , Chappell Michael , Xu Jun
Published: July 2022

Background

Cerebral blood flow (CBF) alterations are involved in the onset and progression of Alzheimer’s disease (AD) and can be a potential biomarker. However, CBF measured by single-delay arterial spin labeling (ASL) for discrimination of mild cognitive impairment (MCI, an early stage of AD) was lack of accuracy. Multi-delay ASL can not only provide CBF quantification but also provide arterial transit time (ATT). Unfortunately, the technique was scarcely applied to the diagnosis of AD. Here, we detected the utility of ASL with 1-delay and 7-delay in ten regions of interest (ROIs) to identify MCI and AD.

Materials and Methods

Pseudocontinuous ASL (pCASL) MRI was acquired on a 3T GE scanner in adults from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) Study of AD cohort, including 26 normal cognition (NC), 37 MCI, and 39 AD. Receiver operating characteristic (ROC) analyses with 1-delay and 7-delay ASL were performed for the identification of MCI and AD. The DeLong test was used to compare ROC curves.

Results

For CBF of 1-delay or 7-delay the AUCs showed moderate-high performance for the AD/NC and AD/MCI comparisons (AUC = 0.83∼0.96) (p < 0.001). CBF of 1-delay performed poorly in MCI/NC comparison (AUC = 0.69) (p < 0.001), but CBF of 7-delay fared well with an AUC of 0.79 (p < 0.001). The combination of CBF and ATT of 7-delay showed higher performance for AD/NC, AD/MCI, and MCI/NC comparisons with AUCs of 0.96, 0.89, and 0.89, respectively (p < 0.001). Furthermore, combination of CBF, ATT, sex, age, APOE ε4, and education improved further the accuracy (p < 0.001). In subgroups analyses, there were no significant differences in CBF of 7-delay ASL for identification of AD or MCI between age subgroups (p > 0.05).

Conclusion

The combination of CBF and ATT with 7-delay ASL showed higher performance for identification of MCI than CBF of 1-delay, when adding to sex, age, APOE ε4 carrier status, and education years, the diagnostic performance was further increased, presenting a potential imaging biomarker in early AD.
Effects of oily fish and its fatty acid intake on non-alcoholic fatty liver disease development among South Korean adults
Authors: Tan Li-Juan , Shin Sangah
Published: July 2022

Background

The benefits of fish fatty acid intake for non-alcoholic fatty liver disease (NAFLD) are rarely reported, although a previous study assessed the relationship between oily fish consumption and the prevalence of NAFLD.

Aims

We investigated whether oily fish and fish-based monounsaturated fatty acids, polyunsaturated fatty acids, and omega-3 fatty acids affect the development of NAFLD in South Korean adults.

Methods

In this large-scale cohort study, 44,139 participants of the Health Examinees study were selected for analysis after 5 years of follow-up. NAFLD is diagnosed with a non-invasive index, the fatty liver index. Using multivariable Cox proportional hazards models, adjusted for age, body mass index, total energy intake, education, physical activity, smoking status, and drinking (alcohol) status, we calculated the hazard ratios and 95% confidence intervals.

Results

For men, NAFLD had no statistically significant associations with quartiles of total oily fish or its fatty acid intake. However, among women, an inverse association was observed (all p for trend <0.05). Regarding the standard deviation (SD) increment of total oily fish or its fatty acid intake by one, all fatty acids from oily fish showed inverse associations for NAFLD in both men and women. After stratified analyses, we found that drinking status and menopause status were independent risk factors for NAFLD. Oily fish or its fatty acid intake has the same benefit pattern on metabolic dysfunction-associated fatty liver disease as NAFLD.

Conclusion

Oily fish and its fatty acid intake showed a preventative benefit for NAFLD and metabolic dysfunction-associated fatty liver disease, especially in South Korean women.
Rapid determination of 103 common veterinary drug residues in milk and dairy products by ultra performance liquid chromatography tandem mass spectrometry
Authors: Guo Xiujuan , Tian Hao , Yang Fan , Fan Sufang , Zhang Jingwen , Ma Junmei , Ai Lianfeng , Zhang Yan
Published: July 2022

A multi-residue method has been developed for the identification and quantification of 103 common veterinary drug residues in milk and dairy Products. This method was based on QuEChERS with dispersive solid-phase where C18 sorbent and anhydrous sodium sulfate were used to sample purification. After evaporation and reconstitution, the samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The mean recovery results were all higher than 60% except ampicillin, pipemidic acid, enoxacin, and estriol, and the relative standard deviation was <20.0%. The limit of quantification ranged between 0.1 and 5 μg/kg for milk and between 0.5 and 25 μg/kg for milk powder. It was successfully used to detect residues of veterinary drug in real samples. This study proposes a simple and fast analytical method for monitoring multi-class veterinary drug residues to ensure food safety.
Characteristics of Gut Microbial Profiles of Offshore Workers and Its Associations With Diet
Authors: Zhang Chunhong , Liang Dong , Li Xiaoxue , Liu Jun , Fan Mengya , Jing Mei , Wang Yifei , Zhang Yu , Fang Yiqun , Li Dan
Published: July 2022

The composition of gut microbiota is not a static state in humans but fluctuates in response to changes in environments, diet, and lifestyle factors. Here, we explored differences in gut microbiota between populations worked offshore and onshore and further studied microbiota-associated variables in offshore workers (OFWs). We investigated the gut microbiota of 168 healthy subjects (offshore: 145 and onshore: 23) using 16S rRNA sequencing. Our results indicated that the marine environment caused significant changes in intestinal microbial structure, which was mainly reflected in the increase in bacterial diversity, changes in composition, and the emergence of more specific bacteria in OFWs. In addition, characteristics of gut microbiota in OFWs were further explored, and the genus Holdemanella was considered a potential contributor to the stable state of health. Besides, some dietary factors, namely, duck, mutton, dairy products, and algae vegetables were identified as the gut microbial covariates in the OFWs cohort and were positively correlated with the genus Holdemanella. This suggests the positive intervention of diet on Holdemanella. Our data highlight, for the first time to our knowledge, that the marine geographical environment plays an important role in shaping the gut mycobiome composition. And diet could be considered as the targeted intervention that alters the composition of the microbiome to improve host health.
Chilling injury of tomato fruit was alleviated under low-temperature storage by silencing Sly-miR171e with short tandem target mimic technology
Authors: Zhao Keyan , Chen Rulong , Duan Wenhui , Meng Lanhuan , Song Hongmiao , Wang Qing , Li Jiangkuo , Xu Xiangbin
Published: July 2022

In this study, the role of Sly-miR171e on post-harvest cold tolerance of tomato fruit was researched. The results showed that overexpression of Sly-miR171e (miR171e-OE) promoted postharvest chilling injury (CI) of tomato fruit at the mature red (MR) and mature green (MG) stage. Contrasted with the wild type (WT) and miR171e-OE fruit, the knockdown of Sly-miR171e (miR171e-STTM) showed a lower CI index, lower hydrogen peroxide (H2O2) content, and higher fruit firmness after harvest. In the fruit of miR171e-STTM, the expression level of GRAS24, CBF1, GA2ox1, and COR, and the GA3 content were ascended, while the expression levels of GA20ox1 and GA3ox1 were descended. The research demonstrated that CI in tomato fruit was alleviated at low temperature storage by silencing Sly-miR171e with short tandem target mimic (STTM) technology. Furthermore, it also provided helpful information for genetic modification of miR171e and control of CI in the postharvest fruit.
Sex-specific effects of maternal dietary carbohydrate quality on fetal development and offspring metabolic phenotype in mice
Authors: Campbell G. Jean , Lucic Fisher Sophie G. , Brandon Amanda E. , Senior Alistair M. , Bell-Anderson Kim S.
Published: July 2022

Objectives

In utero glycemia is an important determinant of fetal growth. Women with gestational diabetes are more likely to deliver large-for-gestational age babies that are at increased risk for obesity. The maternal nutritional state modulates the development of offspring biological systems during the critical periods of gestation and lactation. Carbohydrate typically contributes most of the dietary energy, however, there are very few mechanistic studies investigating the effects of maternal dietary carbohydrate quality on fetal and offspring outcomes. Therefore, we sought to investigate the direct effects of maternal carbohydrate quality on sex-specific offspring metabolic programming.

Methods

Female C57BL/6 mice were fed one of five isocaloric diets: four high-sugar diets based on glucose, sucrose, isomaltulose or fructose (all containing 60% energy as carbohydrate), or a standard, minimally processed, chow diet, and were mated with chow-fed males. Half of the dams were sacrificed for fetus dissection and placental collection, with the remaining giving live birth. All dams were metabolically profiled before and during pregnancy, and pups were similarly profiled at 12 weeks of age.

Results

Overall, glucose-fed dams were heavier and fatter than chow or isomaltulose-fed dams. Female fetuses from glucose and isomaltulose-fed mothers weighed less and had smaller livers, than those from chow-fed mothers, with isomaltulose-fed female fetuses also having decreased placental mass. In contrast, male fetuses responded differently to the maternal diets, with heart mass being significantly increased when their mothers were fed fructose-containing diets, that is, sucrose, isomaltulose and fructose. High-sugar fed female offspring weighed the same, but were significantly fatter, than chow-fed offspring at 12 weeks of age, while glucose and isomaltulose-fed male pups displayed a similar phenotype to their mothers’.

Conclusion

While both glucose and isomaltulose diets constrained fetal growth in females, only placentas from isomaltulose-fed dams were significantly smaller than those from chow-fed mothers, suggesting the mechanisms through which fetal growth is reduced may be different. Female fetuses of isomaltulose-fed mothers were also lighter than sucrose-fed fetuses suggesting the glycemic index, or rate of glucose digestion and absorption, may be an important factor in determining nutrient availability to the growing fetus.
Formation and inhibition mechanism of novel angiotensin I converting enzyme inhibitory peptides from Chouguiyu
Authors: Yang Daqiao , Li Laihao , Li Chunsheng , Chen Shengjun , Deng Jianchao , Yang Shaoling
Published: July 2022

Angiotensin I converting enzyme (ACE) inhibitory peptides from fermented foods exhibit great potential to alleviate hypertension. In this study, the peptide extract from Chouguiyu exhibited a good inhibition effect on ACE, and the inhibition rate was significantly enhanced after fermentation for 8 days. The ACE inhibitory peptides were further identified, followed by their inhibition and formation mechanisms using microbiome technology and molecular docking. A total of 356 ACE inhibitory peptides were predicted using in silico, and most ACE inhibitory peptides increased after fermentation. These peptides could be hydrolyzed from 94 kinds of precursor proteins, mainly including muscle-type creatine kinase, nebulin, and troponin I. P1 (VEIINARA), P2 (FAVMVKG), P4 (EITWSDDKK), P7 (DFDDIQK), P8 (IGDDPKF), P9 (INDDPKIL), and P10 (GVDNPGHPFI) were selected as the core ACE inhibitory peptides according to their abundance and docking energy. The salt bridge and conventional hydrogen bond connecting unsaturated oxygen atoms in the peptides contributed most to the ACE inhibition. The cleavage proteases from the microbial genera in Chouguiyu for preparing these 7 core ACE inhibitory peptides were further analyzed by hydrolysis prediction and Pearson's correlation. The correlation network showed that P7, P8, and P9 were mainly produced by the proteases from LAB including Lactococcus, Enterococcus, Vagococcus, Peptostreptococcus, and Streptococcus, while P1, P2, P4, and P10 were mainly Produced by Aeromonas, Bacillus, Escherichia, and Psychrobacter. This study is helpful in isolating the proteases and microbial strains to directionally produce the responding ACE inhibitory peptides.
The Pulsed Electric Field Assisted-Extraction Enhanced the Yield and the Physicochemical Properties of Soluble Dietary Fiber From Orange Peel
Authors: Fan Rui , Wang Lei , Fan Jingfang , Sun Wanqiu , Dong Hui
Published: July 2022

The study aimed to investigate the effects of pulsed electric field (PEF)-assisted extraction on the yield, physicochemical properties, and structure of soluble dietary fiber (SDF) from orange peel. The results showed that the optinal parameters of PEF assisted extraction SDF was temperature of 45oC with the electric field intensity of 6.0 kV/cm, pulses number of 30, and time of 20min and SDF treated with PEF showed the higher water solubility, water-holding and oil-holding capacity, swelling capacity, emulsifying activity, emulsion stability, foam stability and higher binding capacity for Pb2+, As3+, Cu2+, and higher which resulted from the higher viscosity due to PEF treatment. Compared with the untreated orange peel, the SDF obtained with PEF exhibited stronger antioxidant activities, which was due to its smaller molecular weight (189 vs. 512 kDa). In addition, scanning electron micrograph images demonstrated that the surface of PEF-SDF was rough and collapsed. Overall, it was suggested that PEF treatment could improve the physicochemical properties of SDF from the orange peel and would be the potential extraction technology with high efficiency.
Female infertility and diet, is there a role for a personalized nutritional approach in assisted reproductive technologies? A Narrative Review
Authors: Kohil Amira , Chouliaras Spyridon , Alabduljabbar Shaikha , Lakshmanan Arun Prasath , Ahmed Salma Hayder , Awwad Johnny , Terranegra Annalisa
Published: July 2022

Female infertility is a major public health concern and a global challenge. It is a disorder of the reproductive system, defined as the inability to achieve a clinical pregnancy. Nutrition and other environmental factors are found to impact reproductive health in women as well as the outcome of assisted reproductive technologies (ART). Dietary factors, such as polyunsaturated fatty acids (PUFA), fiber as well as the intake of Mediterranean diet appear to exert beneficial effects on female reproductive outcomes. The exact mechanisms associating diet to female fertility are yet to be identified, although genomic, epigenomic, and microbial pathways may be implicated. This review aims to summarize the current knowledge on the impact of dietary components on female reproduction and ART outcomes, and to discuss the relevant interplay of diet with genome, epigenome and microbial composition.
Intrauterine Growth Restriction Induces Adulthood Chronic Metabolic Disorder in Cardiac and Skeletal Muscles
Authors: Li Ping , He Lewei , Lan Yue , Fang Jie , Fan Zhenxin , Li Yifei
Published: July 2022

Objective

Although population-based studies of intrauterine growth restriction (IUGR) demonstrated a series of postnatal complications, several studies identified that IUGR could definitely cause dysfunction of metabolism of cardiac and skeletal muscles in the perinatal period and early life. However, it is still unknown if such metabolic alternation would remain for long term or not, and whether normal protein diet administration postnatally would protect the IUGR offsprings from a “catch-up growth” and be able to reverse the premature metabolic remodeling.

Materials and Methods

We established an IUGR rat model with pregnant rats and a low-protein diet, and the developmental phenotypes had been carefully recorded. The cardiac and skeletal muscles had been collected to undergo RNA-seq.

Results

According to a series of comparisons of transcriptomes among various developmental processes, programmed metabolic dysfunction and chronic inflammation activity had been identified by transcriptome sequencing in IUGR offsprings, even such rats presented a normal developmental curve or body weight after normal postnatal diet feeding.

Conclusion

The data revealed that IUGR had a significant adverse impact on long-term cardiovascular function in rats, even they exhibit good nutritional status. So that, the fetal stage adverse events would encode the lifelong disease risk, which could hide in young age. This study remaindered that the research on long-term molecular changes is important, and only nutrition improvement would not totally reverse the damage of IUGR.
Evaluation of the association between haemoglobin levels and preterm birth at Khartoum, Sudan: A hospital-based study
Authors: Elmugabil Abdelmageed , Alhabrdi Nadiah M. , Rayis Duria A. , Al-Wutayd Osama , Adam Ishag
Published: July 2022

Objective

The objective of this study was to determine the association between haemoglobin level and PB.

Methods

A cross-sectional study was conducted in Khartoum, Sudan. Questionnaires on demographics and medical and obstetric factors were completed. A logistic regression analysis was performed.

Results

Of the 1,716 pregnant women, approximately two-thirds (65.7%) had anaemia (haemoglobin < 11 g/dl) and six (0.3%) had severe anaemia (haemoglobin < 8 g/dl). Of the 1,716 women, 283 (16.5%) had a PB. In multivariable logistic regression, parity (AOR = 1.15, 95% CI = 1.09–1.21, P < 0.001) was positively associated with PB. Compared to those with haemoglobin levels of 10–10.9 g/dl, pregnant women with haemoglobin levels of 8–8.9 (AOR = 0.41, 95% CI = 0.22–0.77), 9–9.9 (AOR = 0.59, 95% CI = 0.38–0.91), and 11–11.9 g/dl (AOR = 0.53, 95% CI = 0.36–0.77) were at a lower risk of PB. Women with haemoglobin levels of 12–13 g/dl were at a higher risk of PB (AOR = 1.62, 95% CI = 1.06–2.45). There was no significant association between women with haemoglobin levels < 8 g/dl and > 13 g/dl and PB.

Conclusion

This study showed different levels of association between haemoglobin levels and PB.
Palm Lipid Emulsion Droplet Crystallinity and Gastric Acid Stability in Relation to in vitro Bioaccessibility and in vivo Gastric Emptying
Authors: Hamad Samar , Chen Run , Zhou Zhitong , Nasr Pedram , Li Ye Ling , Rafiee Tari Niloufar , Rogers Michael A. , Wright Amanda J.
Published: July 2022

It is poorly understood how the physical state of emulsified triacylglycerol (TAG) alters colloidal behavior in the gastrointestinal tract to modulate lipid digestion and absorption. We, therefore, aimed to investigate the individual and combined effects on fatty acid (FA) bioaccessibility using the dynamic TIM-1 in vitro digestion model and integrate the results with those from a human clinical study. Four 20% oil-in-water emulsions with overlapping particle size distributions contained either partially crystalline solid (palm stearin) or liquid (palm olein) lipid droplets at 37°C and either the colloidally acid-stable Tween 80 (2.2%) or acid-unstable Span 60 (2.5%) emulsifier. Experimental meals were fed to the TIM-1, and jejunal and ileal dialysates were analyzed over 6 h to measure free FA concentration. Cumulative FA bioaccessibility was significantly higher for the liquid stable emulsion compared to all others (p < 0.05), which did not differ (p > 0.05). Emulsified TAG physical state was associated with differences in overall bioaccessibility (higher for liquid state TAG) in the colloidally stable emulsions, but this difference was blunted in droplets susceptible to acidic flocculation. In contrast, human postprandial TAG concentrations did not differ significantly between the emulsions. The discrepancy may relate to differences in in vivo gastric emptying (GE) as evidenced by ultrasonography. When the in vivo differences in GE were accounted for in follow-up TIM-1 experiments, the findings aligned more closely. Cumulative FA bioaccessibility for the liquid stable emulsion no longer differed significantly from the other emulsions, and SU’s bioaccessibility was the lowest, consistent with the in vivo observations. This work highlights the potential for TAG physical state and colloidal stability to interactively alter behavior in the gastrointestinal tract with implications for FA absorption, and the importance of establishing and improving in vitro–in vivo correlations in food-nutrition research.
The Burden of Cancer, Government Strategic Policies, and Challenges in Pakistan: A Comprehensive Review
Authors: Ali Anwar , Manzoor Muhammad Faisal , Ahmad Nazir , Aadil Rana Muhammad , Qin Hong , Siddique Rabia , Riaz Sakhawat , Ahmad Arslan , Korma Sameh A. , Khalid Waseem , Aizhong Liu
Published: July 2022

Cancer is a severe condition characterized by uncontrolled cell division and increasing reported mortality and diagnostic cases. In 2040, an estimated 28.4 million cancer cases are expected to happen globally. In 2020, an estimated 19.3 million new cancer cases (18.1 million excluding non-melanoma skin cancer) had been diagnosed worldwide, with around 10.0 million cancer deaths. Breast cancer cases have increased by 2.26 million, lung cancer by 2.21 million, stomach by 1.089 million, liver by 0.96 million, and colon cancer by 1.93 million. Cancer is becoming more prevalent in Pakistan, with 19 million new cancer cases recorded in 2020. Food adulteration, gutkha, paan, and nutritional deficiencies are major cancer risk factors that interplay with cancer pathogenesis in this country. Government policies and legislation, cancer treatment challenges, and prevention must be revised seriously. This review presents the current cancer epidemiology in Pakistan to better understand cancer basis. It summarizes current cancer risk factors, causes, and the strategies and policies of the country against cancer.
Assessing Bioavailability and Bioactivity of 4-Hydroxythiazolidine-2-Thiones, Newly Discovered Glucosinolate Degradation Products Formed During Domestic Boiling of Cabbage
Authors: Hoffmann Holger , Ott Christiane , Raupbach Jana , Andernach Lars , Renz Matthias , Grune Tilman , Hanschen Franziska S.
Published: July 2022

Glucosinolates are plant secondary metabolites found in cruciferous vegetables (Brassicaceae) that are valued for their potential health benefits. Frequently consumed representatives of these vegetables, for example, are white or red cabbage, which are typically boiled before consumption. Recently, 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were identified as a class of thermal glucosinolate degradation products that are formed during the boiling of cabbage. Since these newly discovered compounds are frequently consumed, this raises questions about their potential uptake and their possible bioactive functions. Therefore, 3-allyl-4-hydroxythiazolidine-2-thione (allyl HTT) and 4-hydroxy-3-(4-(methylsulfinyl) butyl)thiazolidine-2-thione (4-MSOB HTT) as degradation products of the respective glucosinolates sinigrin and glucoraphanin were investigated. After consumption of boiled red cabbage broth, recoveries of consumed amounts of the degradation products in urine collected for 24 h were 18 ± 5% for allyl HTT and 21 ± 4% for 4-MSOB HTT (mean ± SD, n = 3). To investigate the stability of the degradation products during uptake and to elucidate the uptake mechanism, both an in vitro stomach and an in vitro intestinal model were applied. The results indicate that the uptake of allyl HTT and 4-MSOB HTT occurs by passive diffusion. Both compounds show no acute cell toxicity, no antioxidant potential, and no change in NAD(P)H dehydrogenase quinone 1 (NQO1) activity up to 100 μM. However, inhibition of glycogen synthase kinases-3 (GSK-3) in the range of 20% for allyl HTT for the isoform GSK-3β and 29% for 4-MSOB HTT for the isoform GSK-3α at a concentration of 100 μM was found. Neither health-promoting nor toxic effects of 3-alk(en)yl-4-hydroxythiazolidine-2-thiones were found in the four tested assays carried out in this study, which contrasts with the properties of other glucosinolate degradation products, such as isothiocyanates.
Effects of omega-3 supplementation on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus: A randomized clinical trial
Authors: Khorshidi Masoud , Sayyari Aliakbar , Aryaeian Naheed , Olang Beheshteh , Alaei Mohammadreza , Khalili Mitra , Hosseini Amirhossein , Salehi Masoud
Published: July 2022

Background

Vascular dysfunction is a major complication of diabetes mellitus that leads to cardiovascular disease (CVD). This study aimed to examine the effects of omega-3 consumption on endothelial function, vascular structure, and metabolic parameters in adolescents with type 1 diabetes mellitus (T1DM).

Methods

In this randomized, double-blind, placebo-controlled clinical trial, 51 adolescents (10–18 years) with T1DM completed the study. Patients received 600 mg/day [containing 180 mg eicosapentaenoic acid (EPA) and 120 mg docosahexaenoic acid (DHA)] of omega-3 or placebo for 12 weeks. Flow-mediated dilation (FMD), carotid intima-media thickness (CIMT), high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, blood urea nitrogen (BUN), creatinine, fasting blood sugar (FBS), hemoglobin A1C (HbA1c), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), serum insulin (SI), urine albumin-creatinine ratio (uACR), blood pressure, and anthropometric indices were assessed at the baseline and after the intervention.

Results

Following supplementation, omega-3 significantly increased FMD (3.1 ± 4.2 vs. −0.6 ± 4%, p = 0.006) and decreased TG (−7.4 ± 10.7 vs. −0.1 ± 13.1 mg/dl, p = 0.022) in comparison with the placebo group. However, no significant difference was observed regarding CIMT (-0.005 ± 0.036 vs. 0.003 ± 0.021 mm, p = 0.33). Although hs-CRP was significantly decreased within the omega-3 group (p = 0.031); however, no significant change was observed compared to placebo group (p = 0.221). Omega-3 supplementation had no significant effect on other variables.

Conclusion

Given the elevation in FMD and reduction in TG, omega-3 supplementation can improve vascular function and may reduce the risk of cardiovascular disease in adolescents with T1DM patients.
The In-Vitro Antitumor Effects of AST-3424 Monotherapy and Combination Therapy With Oxaliplatin or 5-Fluorouracil in Primary Liver Cancer
Authors: Zhang Yu , Qin Shukui , Chao Jiaojiao , Luo Yan , Sun Yandi , Duan Jianxin
Published: July 2022

Background

Primary liver cancer (PLC) is a common and highly lethal malignancy in the world. Approximately 85% of PLC is hepatocellular carcinoma (HCC), and this study mainly focuses on HCC. The onset of liver cancer is insidious and often complicated with basic liver disease. Meanwhile, its clinical symptoms are atypical, and the degree of malignancy is high. What is worse is that its treatment is difficult, and the prognosis is poor. All these factors make its mortality close to its incidence. AST-3424 is a prodrug of a potent nitrogen mustard, which targets the tumor by its specific and selective mode of activation and results in the concentration of the drug in the tumor and plays a higher intensity of antitumor effect with reduced side effects. The purpose of this study was to explore the in-vitro antitumor activity and mechanism of AST-3424 monotherapy and combination therapy with oxaliplatin (OXA) or 5-fluorouracil (5-Fu). Moreover, it can provide an experimental basis for further studies.

Methods

Tumor growth of HCC cells was examined by using the Cell Counting Kit-8 (CCK-8), flow cytometry, and clone formation assays. Tumor migration of HCC cells was examined by using the Transwell assay. The in-vitro antitumor activity of AST-3424 monotherapy and combination therapy with OXA and 5-Fu was quantified by growth and metastasis inhibition rate. The underlying molecular mechanism was investigated by using Western blotting.

Results

The inhibiting effects of AST-3424 were significant in both HepG2 cells and PLC/PRF/5 cells. Moreover, HepG2 cells showed higher sensitivity to AST-3424. With increasing AST-3424 concentration, AKR1C3 protein expression level was downregulated significantly. The inhibition of AST-3424 was significantly higher than OXA, 5-Fu, Sor (sorafenib), and Apa (apatinib) in both HCC cells. AST-3424 monotherapy and combination therapy with OXA or 5-Fu all strongly inhibited the proliferation of HCC cells, blocked HCC cells in the S phase, promoted apoptosis induction, and suppressed the migration of HCC cells. Among them, the antitumor effect of AST-3424 in combination with OXA was obviously enhanced. Western blotting analysis demonstrated the regulation of P21, Bax, Caspase3, PARP, MMP-2, MMP-9, and p-Smad proteins in the presence of AST-3424 monotherapy and combination therapy with OXA or 5-Fu, indicating that its antitumor mechanisms may be associated with the regulation of the TGF-β signaling cascade.

Conclusion

The in-vitro studies revealed that AST-3424 in combination with both OXA and 5-Fu showed an increased antitumor effect, and the combination with OXA resulted in a synergistic effect. Together with the in-vitro results, additional in-vitro and in-vivo studies are warranted to further certify its antitumor effects and explore more potential antitumor mechanisms.
Biotransformation of Abiraterone Into Five Characteristic Metabolites by the Rat Gut Microbiota and Liver Microsomes
Authors: Keranmu Adili , Yang Fei-Ya , Wahafu Wasilijiang , Han Su-Jun , Yang Guo-Sheng , Xing Nian-Zeng
Published: July 2022

It is well known that the role of gut microbiota in drug metabolism, especially in oral difficult absorbable drugs. Understanding the gut microbiota could enable us to understand drugs in new ways. The purpose of the study was to investigate explore the metabolites of the anti-prostate cancer drug Abiraterone by examining gut microbiota metabolism and hepatic metabolism in vitro. In this study, five metabolites (M1, M2, M3, M4 and M5) of Abiraterone were discovered using LC/MSn-IT-TOF. Four isomeric metabolites M1-M4 were found in liver microsome. M5 was found in the intestinal contents of Sprague-Dawley rats with a molecular weight of 388.31. Among them, M4 was found to be Abiraterone N-Oxide by comparison with the standard sample. After further comparing the metabolic behavior of Abiraterone in rat gut microbiota and liver microsomes, we delineated the possible metabolic pathways of Abiraterone. In conclusion, Abiraterone is metabolized specifically in liver microsomes and gut microbiota. This study can provide a theoretical basis for elucidating the metabolic mechanism of Abiraterone and guide its rational application in clinic.
Label-Free Delineation of Human Uveal Melanoma Infiltration With Pump–Probe Microscopy
Authors: Zhang Bohan , Yao Tengteng , Chen Yaxin , Wang Chuqiao , Bao Yongyang , Wang Zhaoyang , Zhao Keke , Ji Minbiao
Published: July 2022

Uveal melanoma (UM) is the most frequent primary intraocular malignancy in adults, characterized by melanin depositions in melanocytes located in the uveal tract in the eyes. Differentiation of melanin species (eumelanin and pheomelanin) is crucial in the diagnosis and management of UM, yet it remains inaccessible for conventional histology. Here, we report that femtosecond time-resolved pump-probe microscopy could provide label-free and chemical-specific detection of melanin species in human UM based on their distinct transient relaxation dynamics at the subpicosecond timescale. The method is capable of delineating the interface between melanoma and paracancerous regions on various tissue conditions, including frozen sections, paraffin sections, and fresh tissues. Moreover, transcriptome sequencing was conducted to confirm the active eumelanin synthesis in UM. Our results may hold potential for sensitive detection of tumor boundaries and biomedical research on melanin metabolism in UM.
Research Progress on Long Noncoding RNAs and N6-Methyladenosine in Hepatocellular Carcinoma
Authors: Zhang Wenjie , Wu Wenlong , Meng Qiang , Yang Long , Yuan Juzheng , Tian Zelin , Ding Rui , Zhang Xuan , Wang Jianlin , Tao Kaishan
Published: July 2022

N6-methyladenosine (m6A) is an epigenetic modification that widely exists in long noncoding RNAs (lncRNAs) and is involved in the regulation of oncogenes or tumor suppressor genes that form complex enzymes to affect the occurrence of tumors. The abnormal modification of m6A methylation can alter the overall m6A level and thus contribute to the malignant biological behaviors of hepatocellular carcinoma (HCC). LncRNAs related to m6A methylation are involved in lipogenesis, the proliferation, migration and invasion of HCC cells, the stemness of tumor cells and sorafenib resistance. In this review, we systematically elaborated the occurrence mechanism of lncRNA and m6A methylation modification in HCC and the effect of m6A methylation modification of lncRNA on the occurrence of HCC, suggesting that the combination of m6A methylation modification and lncRNA will be more meaningful as molecular markers or prognostic markers. It is helpful to provide further ideas for exploring the pathogenesis of HCC and identifying new targets for HCC treatment and diagnosis and achieve precise individual treatment of liver cancer.
Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database
Authors: Jiao Dechuang , Ma Youzhao , Zhu Jiujun , Dai Hao , Yang Yue , Zhao Yajie , Guo Xuhui , Liu Zhenzhen
Published: July 2022

Objective

This study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010–2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan–Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer–specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses.

Results

Among the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, P < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753–0.797, P < 0.001) and OS (HR = 0.667, 95% CI = 0.653–0.681, P < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years.

Conclusions

In conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.
Long-Term Disease Control After locoregional Pelvic Chemoradiation in Patients with Advanced Anal Squamous Cell Carcinoma
Authors: Grave Athénaïs , Blanc Julie , De Bari Berardino , Pernot Mandy , Boulbair Fatiha , Noirclerc Monique , Vienot Angélique , Kim Stefano , Borg Christophe , Boustani Jihane
Published: July 2022

Introduction

The incidence of metastatic squamous cell carcinoma of the anus (SCCA) is increasing. Even if systemic docetaxel, cisplatin, and 5-Fluorouracil (DCF) provide a high rate of long-term remission, the role of pelvic chemoradiation (CRT) is unknown in this setting. We reported the safety and efficacy of local CRT in patients with synchronous metastatic SCCA who achieved objective response after upfront DCF.

Methods

Patients included in Epitopes HPV01 or Epitopes HPV02 or SCARCE trials and treated with DCF followed by pelvic CRT were included. Concurrent chemotherapy was based on mitomycin (MMC) (10 mg/m² for two cycles) and fluoropyrimidine (capecitabine 825 mg/m² twice a day at each RT treatment day or two cycles of intra-venous 5FU 1000 mg/m² from day 1 to day 4). Primary endpoints were safety, local complete response rate, and local progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and metastasis-free survival (MFS).

Results

From 2013 to 2018, 16 patients received DCF followed by a complementary pelvic CRT for advanced SCCA. Median follow-up was 42 months [range, 11-71]. All patients received the complete radiation dose. Compliance to concurrent CT was poor. Overall, 13/15 of the patients (87%) had at least one grade 1-2 acute toxicity and 11/15 of the patients (73%) had at least one grade 3-4 toxicity. There was no treatment-related death. The most frequent grade 3-4 adverse effects were neutropenia (36%), dermatitis (40%), and anitis (47%). Eleven patients (73%) had at least one chronic grade 1 or 2 toxicity. One patient had a grade 4 chronic rectitis (7%). Complete local response rate was 81% at first evaluation and 62.5% at the end of the follow-up. Median local PFS was not reached and the 3-year local PFS was 77% (95%CI 76.8-77).

Conclusions

In patients with metastatic SCCA who had a significant objective response after upfront DCF, local CRT was feasible with high complete local response rate. The good local control rate, despite interruptions due to toxicities and low CT compliance, underline the role of pelvic RT. The high rate of toxicity prompts the need to adapt CRT regimen in the metastatic setting.
Clinical M2 Macrophage-Related Genes Can Serve as a Reliable Predictor of Lung Adenocarcinoma
Authors: Xu Chaojie , Song Lishan , Yang Yubin , Liu Yi , Pei Dongchen , Liu Jiabang , Guo Jianhua , Liu Nan , Li Xiaoyong , Liu Yuchen , Li Xuesong , Yao Lin , Kang Zhengjun
Published: July 2022

Background

Numerous studies have found that infiltrating M2 macrophages play an important role in the tumor progression of lung adenocarcinoma (LUAD). However, the roles of M2 macrophage infiltration and M2 macrophage-related genes in immunotherapy and clinical outcomes remain obscure.

Methods

Sample information was extracted from TCGA and GEO databases. The TIME landscape was revealed using the CIBERSORT algorithm. Weighted gene co-expression network analysis (WGCNA) was used to find M2 macrophage-related gene modules. Through univariate Cox regression, lasso regression analysis, and multivariate Cox regression, the genes strongly associated with the prognosis of LUAD were screened out. Risk score (RS) was calculated, and all samples were divided into high-risk group (HRG) and low-risk group (LRG) according to the median RS. External validation of RS was performed using GSE68571 data information. Prognostic nomogram based on risk signatures and other clinical information were constructed and validated with calibration curves. Potential associations of tumor mutational burden (TMB) and risk signatures were analyzed. Finally, the potential association of risk signatures with chemotherapy efficacy was investigated using the pRRophetic algorithm.

Results

Based on 504 samples extracted from TCGA database, 183 core genes were identified using WGCNA. Through a series of screening, two M2 macrophage-related genes (GRIA1 and CLEC3B) strongly correlated with LUAD prognosis were finally selected. RS was calculated, and prognostic risk nomogram including gender, age, T, N, M stage, clinical stage, and RS were constructed. The calibration curve shows that our constructed model has good performance. HRG patients were suitable for new ICI immunotherapy, while LRG was more suitable for CTLA4-immunosuppressive therapy alone. The half-maximal inhibitory concentrations (IC50) of the four chemotherapeutic drugs (metformin, cisplatin, paclitaxel, and gemcitabine) showed significant differences in HRG/LRG.

Conclusions

In conclusion, a comprehensive analysis of the role of M2 macrophages in tumor progression will help predict prognosis and facilitate the advancement of therapeutic techniques.