Miracle-dz/UniFAR-FTUs huggingface dataset:
Ligustrazine induces viability, suppresses apoptosis and autophagy of retinal ganglion cells with ischemia/reperfusion injury through the PI3K/Akt/mTOR signaling pathway

ABSTRACT Ligustrazine, an alkaloid monomer extracted from Chuanxiong Rhizoma, has the function of protecting nerve cells. However, the effect and mechanism of ligustrazine on retinal ischemia/reperfusion (I/R) injury still need to be clarified. In our study, retinal ganglion cells (RGC-5) were used to establish a retinal I/R injury model by anaerobic cultivation. Cell viability, autophagy, and apoptosis were evaluated by cell counting kit 8 assay, transmission electron microscopy, and TUNEL staining after treatment with ligustrazine, PI3K inhibitor Ly294002, and/or mTOR inhibitor rapamycin, respectively. Besides, the levels of PI3K/Akt/mTOR pathway and autophagy-related proteins were determined by western blot. Moreover, one-way ANOVA was adopted for inter-group comparisons of measurement data. Our results demonstrated that low-concentration ligustrazine significantly enhanced cell viability and suppressed cell autophagy and apoptosis of RGC-5 cells after I/R injury, suggesting the protective effect of low-concentration ligustrazine on retinal I/R injury. Moreover, the alleviating effect of ligustrazine on RGC-5 with retinal I/R injury was mechanistically associated with the activation of the PI3K/Akt/mTOR pathway. In conclusion, low-concentration ligustrazine has a significant protective effect on RGC-5 cells with retinal I/R injury by activating the PI3K/Akt/mTOR pathway. Graphical abstract
α‐Synuclein evokes NLRP3 inflammasome‐mediated IL‐1β secretion from primary human microglia

Synucleinopathies such as Parkinson's disease (PD) are hallmarked by α‐synuclein (α‐syn) pathology and neuroinflammation. This neuroinflammation involves activated microglia with increased secretion of interleukin‐1β (IL‐1β). The main driver of IL‐1β secretion from microglia is the NLRP3 inflammasome. A critical link between microglial NLRP3 inflammasome activation and the progression of both α‐syn pathology and dopaminergic neurodegeneration has been identified in various PD models in vivo. α‐Syn is known to activate the microglial NLRP3 inflammasome in murine models, but its relationship to this inflammasome in human microglia has not been established. In this study, IL‐1β secretion from primary mouse microglia induced by α‐syn fibrils was dependent on NLRP3 inflammasome assembly and caspase‐1 activity, as previously reported. We show that exposure of primary human microglia to α‐syn fibrils also resulted in significant IL‐1β secretion that was dependent on inflammasome assembly and involved the recruitment of caspase‐1 protein to inflammasome scaffolds as visualized with superresolution microscopy. While canonical IL‐1β secretion was clearly dependent on caspase‐1 enzymatic activity, this activity was less clearly involved for α‐syn‐induced IL‐1β secretion from human microglia. This work presents similarities between primary human and mouse microglia in the mechanisms of activation of the NLRP3 inflammasome by α‐syn, but also highlights evidence to suggest that there may be a difference in the requirement for caspase‐1 activity in IL‐1β output. The data represent a novel characterization of PD‐related NLRP3 inflammasome activation in primary human microglia and further implicate this mechanism in the pathology underlying PD.
Nicorandil decreases oxidative stress in slow‐ and fast‐twitch muscle fibers of diabetic rats by improving the glutathione system functioning

Myopathy is a common complication of any diabetes type, consisting in failure to preserve mass and muscular function. Oxidative stress has been considered one of the main causes for this condition. This study aimed to search if Nicorandil, a KATP channel opener, could protect slow‐ and fast‐twitch diabetic rat muscles from oxidative stress, and to unveil its possible mechanisms.
Development and Validation of Questionnaire to Assess Knowledge about Cervical Cancer among Women Aged 20 to 65 years in Oman

Objective: This study aimed to develop and validate a questionnaire to assess awareness of cervical cancer, its risk factors, and methods of prevention among Arabic-speaking women aged 20 years and over. Methods: The study took place at primary healthcare institutions, Al Buraimi Governorate, Oman, between November 2018 to February 2019. In phase I, seventy items concerning cervical cancer and its prevention were generated through a literature review. In phase 2, the questionnaire was validated through calculating the content validity index (CVI) for both item level (I-CVI) and the scale level (S-CVI), in this phase a shortened English questionnaire of 55 items was formed, then rigorously translated to the Arabic language in phase III. The questionnaire was tested for reliability in two stages: A pilot and a large field test in phase IV. Results: A total of 55 out of 70 items formed the final version of the questionnaire. The final instrument had an S-CVI/Ave of 0.92. The questionnaire called the Knowledge in Cervical Cancer and Prevention Methods 55-items (KCCPM-55). The Cronbach alpha coefficient was 0.940 for the whole questionnaire, and ranged between 0.57 to 0.93 for each of the domains. Test-retest reliability was examined in a subsample of the total participants sample (r = 0.769, p < 0.001). Conclusion: The KCCPM-55 has been successfully developed in the Arabic language and found to be a valid and reliable instrument for assessing the level of knowledge about cervical cancer and prevention methods among women aged 20 to 65 years in Oman.
Mitochondrial translation deficiency impairs NAD+‐mediated lysosomal acidification

Mitochondrial translation dysfunction is associated with neurodegenerative and cardiovascular diseases. Cells eliminate defective mitochondria by the lysosomal machinery via autophagy. The relationship between mitochondrial translation and lysosomal function is unknown. In this study, mitochondrial translation‐deficient hearts from p32‐knockout mice were found to exhibit enlarged lysosomes containing lipofuscin, suggesting impaired lysosome and autolysosome function. These mice also displayed autophagic abnormalities, such as p62 accumulation and LC3 localization around broken mitochondria. The expression of genes encoding for nicotinamide adenine dinucleotide (NAD+) biosynthetic enzymes—Nmnat3 and Nampt—and NAD+ levels were decreased, suggesting that NAD+ is essential for maintaining lysosomal acidification. Conversely, nicotinamide mononucleotide (NMN) administration or Nmnat3 overexpression rescued lysosomal acidification. Nmnat3 gene expression is suppressed by HIF1α, a transcription factor that is stabilized by mitochondrial translation dysfunction, suggesting that HIF1α‐Nmnat3‐mediated NAD+ production is important for lysosomal function. The glycolytic enzymes GAPDH and PGK1 were found associated with lysosomal vesicles, and NAD+ was required for ATP production around lysosomal vesicles. Thus, we conclude that NAD+ content affected by mitochondrial dysfunction is essential for lysosomal maintenance.
Silica-Based Bioactive Glasses and Their Applications in Hard Tissue Regeneration: A Review

Regenerative medicine is a field that aims to influence and improvise the processes of tissue repair and restoration and to assist the body to heal and recover. In the field of hard tissue regeneration, bio-inert materials are being predominantly used, and there is a necessity to use bioactive materials that can help in better tissue–implant interactions and facilitate the healing and regeneration process. One such bioactive material that is being focused upon and studied extensively in the past few decades is bioactive glass (BG). The original bioactive glass (45S5) is composed of silicon dioxide, sodium dioxide, calcium oxide, and phosphorus pentoxide and is mainly referred to by its commercial name Bioglass. BG is mainly used for bone tissue regeneration due to its osteoconductivity and osteostimulation properties. The bioactivity of BG, however, is highly dependent on the compositional ratio of certain glass-forming system content. The manipulation of content ratio and the element compositional flexibility of BG-forming network developed other types of bioactive glasses with controllable chemical durability and chemical affinity with bone and bioactivity. This review article mainly discusses the basic information about silica-based bioactive glasses, including their composition, processing, and properties, as well as their medical applications such as in bone regeneration, as bone grafts, and as dental implant coatings.
The Protective Role of Butyrate against Obesity and Obesity-Related Diseases

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.
Electroencephalography, Magnetoencephalography, and Cognitive Reserve: A Systematic Review

Abstract Objective Cognitive reserve (CR) is the capacity to adapt to (future) brain damage without any or only minimal clinical symptoms. The underlying neuroplastic mechanisms remain unclear. Electrocorticography (ECOG), electroencephalography (EEG), and magnetoencephalography (MEG) may help elucidate the brain mechanisms underlying CR, as CR is thought to be related to efficient utilization of remaining brain resources. The purpose of this systematic review is to collect, evaluate, and synthesize the findings on neural correlates of CR estimates using ECOG, EEG, and MEG. Method We examined articles that were published from the first standardized definition of CR. Eleven EEG and five MEG cross-sectional studies met the inclusion criteria: They concerned original research, analyzed (M)EEG in humans, used a validated CR estimate, and related (M)EEG to CR. Quality assessment was conducted using an adapted form of the Newcastle–Ottawa scale. No ECOG study met the inclusion criteria. Results A total of 1383 participants from heterogeneous patient, young and older healthy groups were divided into three categories by (M)EEG methodology: Eight (M)EEG studies employed event-related fields or potentials, six studies analyzed brain oscillations at rest (of which one also analyzed a cognitive task), and three studies analyzed brain connectivity. Various CR estimates were employed and all studies compared different (M)EEG measures and CR estimates. Several associations between (M)EEG measures and CR estimates were observed. Conclusion Our findings support that (M)EEG measures are related to CR estimates, particularly in healthy individuals. However, the character of this relationship is dependent on the population and task studied, warranting further studies.
Prevalence and features of impaired glucose tolerance in young underweight Japanese women.

OBJECTIVE In Japan, while it is known that underweight women over the age 40 years have a high risk for type 2 diabetes, there is a lack of clarity on the association between glucose tolerance and underweight in younger women. Accordingly, we aimed to investigate the prevalence and features of impaired glucose tolerance (IGT) in young Japanese underweight women. DESIGNS AND METHODS In this cross-sectional study, we recruited 56 normal weight and 98 underweight young Japanese women and evaluated their glucose tolerance levels using an oral glucose tolerance test. Then, we compared the clinical characteristics associated with normal glucose tolerance (NGT) and IGT in the underweight women. Insulin secretion, whole-body insulin sensitivity, and adipose tissue insulin resistance values were measured using the insulinogenic index, whole-body insulin sensitivity index (Matsuda index), and adipose insulin resistance index (Adipo-IR), respectively. Fitness level (peak VO2) was measured using an ergometer. RESULTS The prevalence of IGT was higher in the underweight women than the normal weight women (13.3% vs 1.8%). The underweight women with IGT showed a lower insulinogenic index, lower peak VO2 and Matsuda index, and a higher fasting free fatty acid level and Adipo-IR than those with NGT. The whole-body composition was comparable between the NGT and IGT groups. CONCLUSIONS The prevalence of IGT was higher in young Japanese women with underweight than those with a normal weight. The underweight women with IGT showed impaired early-phase insulin secretion, low fitness levels, and reduced whole-body and adipose tissue insulin sensitivity levels.
Lactobacillus bile salt hydrolase substrate specificity governs bacterial fitness and host colonization

Significance The transformation of bile acids (BAs) by the gut microbiota is increasingly recognized as an important factor shaping host health. The prerequisite step of BA metabolism is carried out by bile salt hydrolases (BSHs), which are encoded by select gut and probiotic bacteria. Despite their prevalence, the utility of harboring a bsh is unclear. Here, we investigate the role of BSHs encoded by Lactobacillus acidophilus and Lactobacillus gasseri. We show that BA type and BSH substrate preferences affect in vitro and in vivo growth of both species. These findings contribute to a mechanistic understanding of bacterial survival in various BA-rich niches and inform future efforts to leverage BSHs as a therapeutic tool for manipulating the gut microbiota. Primary bile acids (BAs) are a collection of host-synthesized metabolites that shape physiology and metabolism. BAs transit the gastrointestinal tract and are subjected to a variety of chemical transformations encoded by indigenous bacteria. The resulting microbiota-derived BA pool is a mediator of host–microbiota interactions. Bacterial bile salt hydrolases (BSHs) cleave the conjugated glycine or taurine from BAs, an essential upstream step for the production of deconjugated and secondary BAs. Probiotic lactobacilli harbor a considerable number and diversity of BSHs; however, their contribution to Lactobacillus fitness and colonization remains poorly understood. Here, we define and compare the functions of multiple BSHs encoded by Lactobacillus acidophilus and Lactobacillus gasseri. Our genetic and biochemical characterization of lactobacilli BSHs lend to a model of Lactobacillus adaptation to the gut. These findings deviate from previous notions that BSHs generally promote colonization and detoxify bile. Rather, we show that BSH enzymatic preferences and the intrinsic chemical features of various BAs determine the toxicity of these molecules during Lactobacillus growth. BSHs were able to alter the Lactobacillus transcriptome in a BA-dependent manner. Finally, BSHs were able to dictate differences in bacterial competition in vitro and in vivo, defining their impact on BSH-encoding bacteria within the greater gastrointestinal tract ecosystem. This work emphasizes the importance of considering the enzymatic preferences of BSHs alongside the conjugated/deconjugated BA–bacterial interaction. These results deepen our understanding of the BA–microbiome axis and provide a framework to engineer lactobacilli with improved bile resistance and use probiotics as BA-altering therapeutics.
Auditory brainstem responses in aging dark agouti rats

This study examined auditory function across age in the dark agouti (DA) rat strain. Auditory brainstem responses were measured for frequencies 8, 16, and 32 kHz in male and female DA rats from 3 months to 18 months of age. Hearing thresholds and absolute and interpeak latencies were analyzed. Male hearing thresholds remained stable for the first year of life and then significantly increased at 18 months across all frequencies; female hearing remained stable at all tested ages out to 18 months. At 12 months, male DA rats showed significantly longer absolute latencies by age (i.e., compared to 3-month-old males), and sex (compared to 12-month-old females), with no differences in interpeak latencies. At 18 months, female DA rats showed significantly longer absolute latencies with age (compared to 3-month-old females), and sex (compared to 18-month-old males), particularly for the later waves. Female interpeak latencies were also significantly longer with age and by sex for the later waves. This report supports the feasibility of using male dark agouti rats in studies to investigate age-related hearing loss (presbycusis).
Nanowires of α- and β-Bi2O3: phase-selective synthesis and application in photocatalysis

This paper is focused on the first selective synthesis of α-and β-Bi2O3 nanowires by an oxidative metal vapour transport deposition technique. The nanowires growth conditions have been systematically investigated, providing insights into the mechanism of nanowires formation. We make a critical comparison of photocatalytic properties of the α- and β-Bi2O3 nanowires by the photo-degradation of Orange G under visible light. The β-Bi2O3 nanowires have shown the highest photo-catalytic activity under visible light of all the tested samples of Degussa TiO2 P25 and α-/β-Bi2O3 nanowires, which can be interpreted by the narrowest band gap of the β-Bi2O3 nanowires for the most effective harvest of the visible light as well as their smallest size for the most facile transfer of photo-excited electrons and the consequent most effective electron-hole separation.
A Cross-Sectional Study about Knowledge, Awareness and Perception of Risk Factors for Cancer among Cancer-Patients Relatives and Healthy Adults in Ho Chi Minh City, Vietnam

Background and Aims: Although cancer is common in Ho Chi Minh city, Vietnam, the community awareness is still unknown. The primary objective of this study was to examine and compare the knowledge and risk perceptions of cancer possessed by cancer patients - relatives and healthy adults in Ho Chi Minh City, Vietnam. Methods: A cross-sectional study was conducted from June to August 2019. Cancer patients and their relatives were drawn from those who were hospitalized in the Oncology Hospital, Ho Chi Minh City. Healthy individuals were those without a known diagnosis of cancer, and they were drawn from the participants of the Vietnam Osteoporosis Study. A total of 533 participants including 249 patients and relatives (cancerous group) and 284 healthy individuals (healthy group), were asked to respond to a structured questionnaire that was comprised of items concerning cancer knowledge, risk factor perception, and general attitude towards cancer, using Yes, No, or Likert Scale for response. Results: The findings showed that patients hold poorer knowledge of pathology, signs, symptoms, prevention, and treatment and lower awareness of risk factors but more positive attitude towards cancer as compared to their healthy counterparts. Overall, both groups varied in their cancer knowledge, with many areas remain to be improved. Conclusions: Knowledge about cancer and its risk factors should be improved among the general population as well as among those with direct experiences with cancer. Practical implications: The findings provided by this study has major implications for the design of an educational program for cancer patients in clinical settings and awareness programs for the general public as a primary preventive measure for mitigating the cancer burden. Future studies with larger and more diverse samples or qualitative studies exploring the personal narratives of people living with cancer could take advantage from the preliminary data provided by this study.
Non-Steroidal Anti-Inflammatory Drugs: Pharmacokinetics and Mitigation of Procedural-Pain in Cattle

Simple Summary Castration and disbudding, common husbandry procedures used in cattle livestock production industries, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain relief. Although non-steroidal anti-inflammatory drugs (NSAIDs) are used in food-animal production systems, no such pain relief drugs are federally approved in the U.S. for controlling procedural pain in cattle to date. Recent increases in consumer, retailer and producer commitment to improving the welfare of food-animals necessitate a closer look into pain control efforts for livestock. Therefore, this review comprehensively evaluated existing literature to summarize three NSAIDs (meloxicam, flunixin and aspirin) (1) pharmacokinetics and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle represent on-going challenges. Future research should prioritize replication of pain assessment techniques across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of the effectiveness of pain relief drugs. Abstract Common routine management practices in cattle, such as castration and disbudding, are recognized as being painful. In the United States (U.S.), these procedures are frequently performed without pain mitigation and there are currently no drugs federally approved for such use. Non-steroidal anti-inflammatory drugs, such as meloxicam, flunixin meglumine and aspirin, are the most commonly used analgesics in U.S. food-animal production systems. However, the body of research investigating the effectiveness of these pharmaceuticals to control pain in cattle at castration and disbudding has not been comprehensively evaluated. Therefore, this review examined existing literature to summarize meloxicam, flunixin and aspirin (1) pharmacokinetics (PK) and (2) administration outcome in regard to pain control during castration and disbudding procedures, in cattle. Following systematic searches and screening, 47 PK and 44 publications were extracted for data and are presented. The sample size contained notable variability and a general deficiency of validated and replicated methodologies for assessing pain in cattle remain substantial challenges within this research area. Future research should prioritize replication of pain assessment methodologies across different experimental conditions to close knowledge gaps identified by the present study and facilitate examination of analgesic efficacy.