Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy: An important target for natural products in the treatment of bone metabolic diseases

Bone homeostasis depends on a precise dynamic balance between bone resorption and bone formation, involving a series of complex and highly regulated steps. Any imbalance in this process can cause disturbances in bone metabolism and lead to the development of many associated bone diseases. Autophagy, one of the fundamental pathways for the degradation and recycling of proteins and organelles, is a fundamental process that regulates cellular and organismal homeostasis. Importantly, basic levels of autophagy are present in all types of bone-associated cells. Due to the cyclic nature of autophagy and the ongoing bone metabolism processes, autophagy is considered a new participant in bone maintenance. Novel therapeutic targets have emerged as a result of new mechanisms, and bone metabolism can be controlled by interfering with autophagy by focusing on certain regulatory molecules in autophagy. In parallel, several studies have reported that various natural products exhibit a good potential to mediate autophagy for the treatment of metabolic bone diseases. Therefore, we briefly described the process of autophagy, emphasizing its function in different cell types involved in bone development and metabolism (including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, chondrocytes, and osteoclasts), and also summarized research advances in natural product-mediated autophagy for the treatment of metabolic bone disease caused by dysfunction of these cells (including osteoporosis, rheumatoid joints, osteoarthritis, fracture nonunion/delayed union). The objective of the study was to identify the function that autophagy serves in metabolic bone disease and the effects, potential, and challenges of natural products for the treatment of these diseases by targeting autophagy.
Association of concomitant autoimmunity with the disease features and long-term treatment and health outcomes in Celiac disease

Background Celiac disease (CeD) is often accompanied by other autoimmune diseases (AID). However, the association of co-existing autoimmunity with the presentation and treatment success in CeD is unclear. We investigated these issues with a large and well-defined cohort of Finnish patients. Methods Adult CeD patients (n = 806) were collected from multiple heath care sites via nationwide recruitment. They were interviewed, underwent measurement of CeD autoantibodies, and filled out questionnaires to ascertain quality of life (PGWB) and gastrointestinal symptoms (GSRS) after a median of 9.7 years on a gluten-free diet. Data were supplemented retrospectively from patient records. The results were compared between CeD patients with and without a coexisting AID. Results Altogether 185 patients had CeD+AID and 621 had CeD only. At CeD diagnosis, patients with CeD+AID were older (median 42 vs. 36 years, p = 0.010) and had more joint symptoms (9.1 vs. 4.2%, p = 0.011), whereas the groups were comparable in sex, family history of CeD, other presenting symptoms, proportion of screen-detected subjects, and severity of duodenal lesion. During follow-up on gluten-free diet, CeD+AID patients experienced poorer general health (median score 12 vs. 14, p < 0.001) in PGWB, more overall gastrointestinal symptoms (2.1 vs. 1.9, p = 0.001), and constipation (2.0 vs. 1.7, p < 0.001) in GSRS, whereas there was no difference in histological and serological recovery, dietary adherence, use of gluten-free oats, smoking, and presence of regular follow-up. Conclusions Co-existing AID was not significantly associated with the baseline features or with most long-term outcomes in CeD. However, the increased prevalence of gastrointestinal symptoms and reduced poorer self-perceived health during treatment indicates these patients' need for special support.
Why vaccines fail against Piscirickettsiosis in farmed salmon and trout and how to avoid it: A review

Piscirickettsiosis is the most severe, persistent, and damaging disease that has affected the Chilean salmon industry since its origins in the 1980s. As a preventive strategy for this disease, different vaccines have been developed and used over the last 30 years. However, vaccinated salmon and trout frequently die in the sea cages and the use of antibiotics is still high demonstrating the low efficiency of the available vaccines. The reasons why the vaccines fail so often are still debated, but it could involve different extrinsic and intrinsic factors. Among the extrinsic factors, mainly associated with chronic stress, we can distinguish: 1) biotic including coinfection with sea lice, sealions attacks or harmful algal blooms; 2) abiotic including low oxygen or high temperature; and 3) farm-management factors including overcrowding or chemical delousing treatments. Among the intrinsic factors, we can distinguish: 1) fish-related factors including host’s genetic variability (species, population and individual), sex or age; 2) pathogen-related factors including their variability and ability to evade host immune responses; and 3) vaccine-related factors including low immunogenicity and poor matches with the circulating pathogen strain. Based on the available evidence, in order to improve the development and the efficacy of vaccines against P. salmonis we recommend: a) Do not perform efficacy evaluations by intraperitoneal injection of pathogens because they generate an artificial protective immune response, instead cohabitation or immersion challenges must be used; b) Evaluate the diversity of pathogen strains in the field and ensure a good antigenic match with the vaccines; c) Investigate whether host genetic diversity could be improved, e.g. through selection, in favor of better and longer responses to vaccination; d) To reduce the stressful effects at the cage level, controlling the co-infection of pathogens and avoiding fish overcrowding. To date, we do not know the immunological mechanisms by which the vaccines against P. salmonis may or may not generate protection. More studies are required to identify what type of response, cellular or molecular, is required to develop effective vaccines.
A theoretical model reveals specialized synaptic depressions and temporal frequency tuning in retinal parallel channels

In the Outer Plexiform Layer of a retina, a cone pedicle provides synaptic inputs for multiple cone bipolar cell (CBC) subtypes so that each subtype formats a parallelized processing channel to filter visual features from the environment. Due to the diversity of short-term depressions among cone-CBC contacts, these channels have different temporal frequency tunings. Here, we propose a theoretical model based on the hierarchy Linear-Nonlinear-Synapse framework to link the synaptic depression and the neural activities of the cone-CBC circuit. The model successfully captures various frequency tunings of subtype-specialized channels and infers synaptic depression recovery time constants inside circuits. Furthermore, the model can predict frequency-tuning behaviors based on synaptic activities. With the prediction of region-specialized UV cone parallel channels, we suggest the acute zone in the zebrafish retina supports detecting light-off events at high temporal frequencies.
Adrenal insufficiency in patients with Prader-Willi syndrome

The generalized dysfunction of the hypothalamic-pituitary axis in patients with Prader-Willi syndrome (PWS) is the most likely cause of hypogonadism, inadequate growth hormone secretion, excessive appetite and associated obesity, impaired body temperature regulation, and hypothyroidism. The syndrome is also related to an increased risk of central adrenal insufficiency, although its prevalence remains unknown. The results of the studies in which different methods of pharmacological stimulation were used do not provide conclusive outcomes. As a result, there are no clear guidelines with regard to diagnosis, prevention, or long-term care when adrenal insufficiency is suspected in patients with PWS. Currently, most patients with PWS are treated with recombinant human growth hormone (rhGH). It has been confirmed that rhGH therapy has a positive effect on growth, body composition, body mass index (BMI), and potentially on psychomotor development in children with PWS. Additionally, rhGH may reduce the conversion of cortisone to cortisol through inhibition of 11β-hydroxysteroid dehydrogenase type 1. However, its influence on basal adrenal function and adrenal stress response remains unexplained in children with PWS. This paper reviews the literature related to the hypothalamic-pituitary-adrenal axis dysfunction in the PWS patient population with a focus on children.
Treatment decision in a 4-year-old-boy with left ventricular outpouching after advanced hemodynamical flow evaluation with 4Dflow CMR: A case report

Background The present study presents a diagnostic course for the characterization of a congenital left ventricular outpouching (LVO) in a 4-year-old boy with severe neonatal heart failure, evaluating the added value of cardiac magnetic resonance (CMR) 4Dflow. Case presentation A boy, born at full term, presented with heart failure immediately after birth. Echocardiography showed dilated left ventricle with poor function and LVO was initially interpreted as an aneurysm. No infection, inflammation, or other cause for heart failure was found. With intensive medical treatment, the heart function returned to normal, and eventually, all medication was terminated. At follow-up, surgical treatment of the LVO was discussed but after CMR 4Dflow, a thorough evaluation of the function of the left ventricle as well as the LVO was possible and the LVO was determined a double-chambered left ventricle with a good prognosis. Conclusions The present case demonstrates the clinical usability of CMR 4Dflow for improved decision-making and risk assessment, revealing advanced hemodynamic flow patterns with no need for operation.
Fragile sites, chromosomal lesions, tandem repeats, and disease

Expanded tandem repeat DNAs are associated with various unusual chromosomal lesions, despiralizations, multi-branched inter-chromosomal associations, and fragile sites. Fragile sites cytogenetically manifest as localized gaps or discontinuities in chromosome structure and are an important genetic, biological, and health-related phenomena. Common fragile sites (∼230), present in most individuals, are induced by aphidicolin and can be associated with cancer; of the 27 molecularly-mapped common sites, none are associated with a particular DNA sequence motif. Rare fragile sites ( ≳ 40 known), ≤ 5% of the population (may be as few as a single individual), can be associated with neurodevelopmental disease. All 10 molecularly-mapped folate-sensitive fragile sites, the largest category of rare fragile sites, are caused by gene-specific CGG/CCG tandem repeat expansions that are aberrantly CpG methylated and include FRAXA, FRAXE, FRAXF, FRA2A, FRA7A, FRA10A, FRA11A, FRA11B, FRA12A, and FRA16A. The minisatellite-associated rare fragile sites, FRA10B, FRA16B, can be induced by AT-rich DNA-ligands or nucleotide analogs. Despiralized lesions and multi-branched inter-chromosomal associations at the heterochromatic satellite repeats of chromosomes 1, 9, 16 are inducible by de-methylating agents like 5-azadeoxycytidine and can spontaneously arise in patients with ICF syndrome (Immunodeficiency Centromeric instability and Facial anomalies) with mutations in genes regulating DNA methylation. ICF individuals have hypomethylated satellites I-III, alpha-satellites, and subtelomeric repeats. Ribosomal repeats and subtelomeric D4Z4 megasatellites/macrosatellites, are associated with chromosome location, fragility, and disease. Telomere repeats can also assume fragile sites. Dietary deficiencies of folate or vitamin B12, or drug insults are associated with megaloblastic and/or pernicious anemia, that display chromosomes with fragile sites. The recent discovery of many new tandem repeat expansion loci, with varied repeat motifs, where motif lengths can range from mono-nucleotides to megabase units, could be the molecular cause of new fragile sites, or other chromosomal lesions. This review focuses on repeat-associated fragility, covering their induction, cytogenetics, epigenetics, cell type specificity, genetic instability (repeat instability, micronuclei, deletions/rearrangements, and sister chromatid exchange), unusual heritability, disease association, and penetrance. Understanding tandem repeat-associated chromosomal fragile sites provides insight to chromosome structure, genome packaging, genetic instability, and disease.
Editorial: Climate risk management in smallholder agriculture

COPYRIGHT © 2022 Catacutan, Harvey, Öborn and van Noordwijk. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Climate risk management in smallholder agriculture
Genomic reconstruction and features of glycosylation pathways in the apicomplexan Cryptosporidium parasites

Cryptosporidium is a genus of apicomplexan parasites infecting humans or other vertebrates. The majority of the Cryptosporidium species live in host intestines (e.g., C. parvum, C. hominis and C. ubiquitum), but there are a few gastric species (e.g., C. muris and C. andersoni). Among them, C. parvum is the most important zoonotic species, for which a number of glycoproteins have been reported for being involved in the interacting with host cells. However, little is known on the cryptosporidium glycobiology. Information on the glycosylation pathways in Cryptosporidium parasites remains sketchy and only a few studies have truly determined the glycoforms in the parasites. Here we reanalyzed the Cryptosporidium genomes and reconstructed the glycosylation pathways, including the synthesis of N- and O-linked glycans and GPI-anchors. In N-glycosylation, intestinal Cryptosporidium possesses enzymes to make a simple precursor with two terminal glucoses on the long arm (i.e., Glc2Man5GlcNAc2 vs. Glc3Man9GlcNAc2 in humans), but gastric species only makes a simpler precursor containing only the “core” structure (i.e., Man3GlcNAc2). There is an ortholog of glucosidase II (GANAB) in all Cryptosporidium species, for which the authenticity is questioned because it contains no signal peptide and exist in gastric species lacking terminal glucoses for the enzyme to act on. In O-linked glycosylation, all Cryptosporidium species may attach one-unit HexNAc (GalNAc and GlcNAc) and two-unit Fuc-type (Man-Fuc) glycans to the target proteins. Cryptosporidium lacks enzymes to further process N- and O-glycans in the Golgi. The glycosylphosphatidylinositol (GPI)-anchor in Cryptosporidium is predicted to be unbranched and unprocessed further in the Golgi. Cryptosporidium can synthesize limited nucleotide sugars, but possesses at least 12 transporters to scavenge nucleotide sugars or transport them across the ER/Golgi membranes. Overall, Cryptosporidium makes much simpler glycans than the hosts, and the N-glycoforms further differ between intestinal and gastric species. The Cryptosporidium N- and O-glycans are neutrally charged and have limited capacity to absorb water molecules in comparison to the host intestinal mucins that are negatively charged and highly expandable in waters.
Circular RNA hsa_circ_0007990 as a blood biomarker for unruptured intracranial aneurysm with aneurysm wall enhancement

Background Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. Methods We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. Results Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. Conclusion Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.
Gut fungi differentially response to the antipyretic (heat-clearing) and diaphoretic (exterior-releasing) traditional Chinese medicines in Coptis chinensis-conditioned gut microbiota

Antipyretic (heat-clearing) and diaphoretic (exterior-releasing) drugs are two main groups of traditional Chinese medicines (TCMs) possessing anti-microbes and anti-inflammation effects, with the former mainly through clearing pyrogens while the latter through promoting diaphoresis. Although anti-microorganism is a common action of these two kinds of TCMs, their difference in antimicrobial spectrums and their interactions when combinedly used remain unclear. Herein, we prepared aqueous extracts from Coptis chinensis (HL) and other antipyretic or diaphoretic TCMs, orally administrated them to C57BL/6 mice at a clinical dose for fourteen days, and analyzed their impaction on both gut bacteria and fungi using full-length 16 S rRNA gene sequencing and internal transcribed spacer 1/2 (ITS1/2) gene sequencing, respectively. Oral administration of HL significantly changed the structure of gut bacteria but showed little influence on gut fungi. Co-treatment with antipyretic or diaphoretic TCMs alleviated the impact of HL on gut bacteria to a similar degree. However, combined with either heat-clearing or exterior-releasing TCMs significantly strengthened the influence of HL on gut fungi, with the latter superior to the former. The antipyretic TCMs enriched Penicillium spp. while diaphoretic TCMs promoted Fusarium spp. Further analysis revealed that the diaphoretic TCMs-enriched fungi Fusarium spp. were positively related to Akkermansia spp. , a beneficial bacterium that interacts with Toll-like receptor 4 (TLR4) and regulates thermogenesis, thus providing a potential linkage with their pro-diaphoresis effect. Together, our results reveal that gut fungi differentially respond to the impact of heat-clearing and exterior-releasing TCMs on Coptis chinensis-conditioned gut microbiota, which provides insights into their functional characteristics.
Editorial: Treatment of Alzheimer’s disease-discovery of natural products based on neurite outgrowth and neuroprotection

Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Institute of Nutrition and Marine Drugs, Guangdong Ocean University, Zhanjiang, China, Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, Guangdong Pharmaceutical University, Guangzhou, China, Section of Neuromedical Science, Institute of Natural Medicine, University of Toyama, Toyama, Japan
The earlier the initiation of gonadotropin in poor responders in luteal phase stimulation protocols, the better

Introduction Luteal-phase ovarian stimulation has been proved to be feasible for producing competent oocytes/embryos and achieving live births, yet there is no standardized stimulation protocol for luteal-phase ovarian stimulation (LPS). The aim of this study was to explore the optimal timing of gonadotropin initiation in the LPS protocol for poor ovarian responders. Methods This was a retrospective cohort study conducted in the reproductive medicine center of a tertiary hospital. A total of 327 poor responders fulfilling Bologna criteria underwent LPS with IVF/ICSI treatment. HMG and letrozole were administrated after ovulation. Patients were stratified into three groups according to the gonadotropin start day: early, early-mid, and mid-late luteal phase. A freeze-all strategy was performed for all cycles. The duration of ovarian stimulation, total gonadotropin dose, number of oocytes retrieved, implantation rate, clinical pregnancy rate, and live birth rate after frozen/thawed embryo transfer cycles were included for evaluation. Results The group accepted ovarian stimulation in the earlier phase tended to have a shorter duration of ovarian stimulation [8 (7,10) in early luteal group, 9 (8,10.25) in early-mid luteal group, and 11 (10,12) in mid-late luteal group; P <0.001] and lower gonadotropin consumption [1993.35 ± 720.31, 2282.73 ± 703.38, and 2764.83 ± 722.26, respectively; P <0.001]. Logistic regression and multiple linear regression were used to assess the associations between the phase of gonadotropin initiation and duration of ovarian stimulation (or total gonadotropin dose) by adjusting for confounding factors. Compared with the early luteal group, longer ovarian stimulation(>9 days) was more likely to occur in the early-mid and mid-late luteal groups, with the adjusted odds ratios 0.584 (0.327-1.042) and 0.116 (0.049-0.271), respectively (P-trend<0.001). Delayed gonadotropin initiation showed an 113.200 IU increase (95%CI: 70.469, 155.930) per-day in the total gonadotropin dosage. Meanwhile, there were no significant differences in the mean number of oocytes, utilizable embryos, pregnancy outcomes among three groups. Conclusion Although the timing of gonadotropin initiation is not associated with pregnancy outcomes, earlier initiation of gonadotropin therapy after ovulation was associated with a shorter duration of ovarian stimulation and lower gonadotropin consumption in poor responders in LPS.