Miracle-dz/UniFAR-FTUs huggingface dataset:
Loganin Ameliorates Painful Diabetic Neuropathy by Modulating Oxidative Stress, Inflammation and Insulin Sensitivity in Streptozotocin-Nicotinamide-Induced Diabetic Rats

Loganin is an iridoid glycoside with antioxidant, anti-inflammatory, glucose-lowering activities which may address the pathological mechanisms of painful diabetic neuropathy (PDN) related to inflammation, oxidative stress, and hyperglycemia. This study investigated the underlying mechanisms of action of loganin on PDN. The in vivo model of PDN was established by streptozotocin-nicotinamide (STZ-NA) induction in Sprague Dawley (SD) rats. Subsequently, loganin (5 mg/kg) was administered by daily intraperitoneal injection. High-glucose stimulated human SH-SY5Y cells co-incubated with loganin were used to mimic the in vitro model of PDN. Loganin improved PDN rats’ associated pain behaviors (allodynia and hyperalgesia), insulin resistance index (HOMA-IR), and serum levels of superoxide dismutase (SOD), catalase and glutathione. Loganin also reduced pain-associated channel protein CaV3.2 and calcitonin gene-related peptide (CGRP) in the surficial spinal dorsal horn of PDN rats. Loganin inhibited oxidative stress and NF-κB activation and decreased the levels of mRNA and protein of proinflammatory factors IL-1β and TNF-α. Moreover, loganin attenuated insulin resistance by modulating the JNK-IRS-1 (insulin receptor substrate-1)-Akt-GSK3β signaling pathway in PDN rats. These results suggested that loganin improved PDN-mediated pain behaviors by inhibiting oxidative stress-provoked inflammation in the spinal cord, resulting in improved neuropathic pain.
The LEDGF/p75 Integrase Binding Domain Interactome Contributes to the Survival, Clonogenicity, and Tumorsphere Formation of Docetaxel-Resistant Prostate Cancer Cells

Patients with prostate cancer (PCa) receiving docetaxel chemotherapy invariably develop chemoresistance. The transcription co-activator lens epithelium-derived growth factor p75 (LEDGF/p75), also known as DFS70 and PSIP1, is upregulated in several human cancers, including PCa and promotes resistance to docetaxel and other drugs. The C-terminal region of LEDGF/p75 contains an integrase binding domain (IBD) that tethers nuclear proteins, including the HIV-1 integrase and transcription factors, to active chromatin to promote viral integration and transcription of cellular survival genes. Here, we investigated the contribution of the LEDGF/p75 IBD interactome to PCa chemoresistance. Quantitative immunoblotting revealed that LEDGF/p75 and its IBD-interacting partners are endogenously upregulated in docetaxel-resistant PCa cell lines compared to docetaxel-sensitive parental cells. Using specific human autoantibodies, we co-immunoprecipitated LEDGF/p75 with its endogenous IBD-interacting partners JPO2, menin, MLL, IWS1, ASK1, and PogZ, as well as transcription factors c-MYC and HRP2, in docetaxel-resistant cells, and confirmed their nuclear co-localization by confocal microscopy. Depletion of LEDGF/p75 and selected interacting partners robustly decreased the survival, clonogenicity, and tumorsphere formation capacity of docetaxel-resistant cells. These results implicate the LEDGF/p75 IBD interactome in PCa chemoresistance and could lead to novel therapeutic strategies targeting this protein complex for the treatment of docetaxel-resistant tumors.
Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions

Staphylococcus aureus is a frequent cause of ocular surface infections worldwide. Of these surface infections, those involving the cornea (microbial keratitis) are most sight-threatening. S. aureus can also cause conjunctivitis and contact lens-related non-infectious corneal infiltrative events (niCIE). The aim of this study was to determine the rates of resistance of S. aureus isolates to antibiotics and disinfecting solutions from these different ocular surface conditions. In total, 63 S. aureus strains from the USA and Australia were evaluated; 14 were from niCIE, 26 from conjunctivitis, and 23 from microbial keratitis (MK). The minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of all the strains to ciprofloxacin, ceftazidime, oxacillin, gentamicin, vancomycin, chloramphenicol, azithromycin, and polymyxin B were determined. The MIC and MBC of the niCIE strains to contact lens multipurpose disinfectant solutions (MPDSs) was determined. All isolates were susceptible to vancomycin (100%). The susceptibility to other antibiotics decreased in the following order: gentamicin (98%), chloramphenicol (76%), oxacillin (74%), ciprofloxacin (46%), ceftazidime (11%), azithromycin (8%), and polymyxin B (8%). In total, 87% of all the isolates were multidrug resistant and 17% of the isolates from microbial keratitis were extensively drug resistant. The microbial keratitis strains from Australia were usually susceptible to ciprofloxacin (57% vs. 11%; p = 0.04) and oxacillin (93% vs. 11%; p = 0.02) compared to microbial keratitis isolates from the USA. Microbial keratitis isolates from the USA were less susceptible (55%) to chloramphenicol compared to conjunctivitis strains (95%; p = 0.01). Similarly, 75% of conjunctivitis strains from Australia were susceptible to chloramphenicol compared to 14% of microbial keratitis strains (p = 0.04). Most (93%) strains isolated from contact lens wearers were killed in 100% MPDS, except S. aureus 27. OPTI-FREE PureMoist was the most active MPDS against all strains with 35% of strains having an MIC ≤ 11.36%. There was a significant difference in susceptibility between OPTI-FREE PureMoist and Biotrue (p = 0.02). S. aureus non-infectious CIE strains were more susceptible to antibiotics than conjunctivitis strains and conjunctivitis strains were more susceptible than microbial keratitis strains. Microbial keratitis strains from Australia (isolated between 2006 and 2018) were more susceptible to antibiotics in comparison with microbial keratitis strains from the USA (isolated in 2004). Most of the strains were multidrug-resistant. There was variability in the susceptibility of contact lens isolates to MPDSs with one S. aureus strain, S. aureus 27, isolated from niCIE, in Australia in 1997 being highly resistant to all four MPDSs and three different types of antibiotics. Knowledge of the rates of resistance to antibiotics in different conditions and regions could help guide treatment of these diseases.
Nutrition and Digestive Physiology of the Broiler Chick: State of the Art and Outlook

Simple Summary The first week after hatch is the most challenging period in the life of broilers. The digestive tract of the newly hatched chick is immature and must undergo dramatic changes before it can efficiently digest and absorb nutrients. The gut is the vital organ where nutrient digestion and absorption take place. Ontogenic changes that accompany improved digestion and absorption include increased secretion of digestive enzymes, increase in the gut absorptive surface area, and enhanced nutrient transporters. The obvious limiting factors are the secretion and activities of digestive enzymes, and the surface area for absorption. These limitations are overcome as the birds grow older, with concurrent improvements in nutrient utilization. In addition, substantial changes also take place in the physical and functional development of the immune system and intestinal microbial ecology. However, the focus of the current review was on nutrition-related challenges and nutritional approaches to assist the chick during this highly demanding period. Abstract Because the intestine is the primary nutrient supply organ, early development of digestive function in newly hatched chick will enable it to better utilize nutrients, grow efficiently, and achieve the genetic potential of contemporary broilers. Published data on the growth and digestive function of the gastrointestinal tract in neonatal poultry were reviewed. Several potential strategies to improve digestive tract growth and function in newly hatched chick are available and the options include breeder nutrition, in ovo feeding, early access to feed and water, special pre-starter diets, judicious use of feed additives, and early programming.
The Role of the C-Terminal Lysine of S100P in S100P-Induced Cell Migration and Metastasis

S100P protein is a potent inducer of metastasis in a model system, and its presence in cancer cells of patients is strongly associated with their reduced survival times. A well-established Furth Wistar rat metastasis model system, methods for measuring cell migration, and specific inhibitors were used to study pathways of motility-driven metastasis. Cells expressing C-terminal mutant S100P proteins display markedly-reduced S100P-driven metastasis in vivo and cell migration in vitro. These cells fail to display the low focal adhesion numbers observed in cells expressing wild-type S100P, and the mutant S100P proteins exhibit reduced biochemical interaction with non-muscle myosin heavy chain isoform IIA in vitro. Extracellular inhibitors of the S100P-dependent plasminogen activation pathway reduce, but only in part, wild-type S100P-dependent cell migration; they are without effect on S100P-negative cells or cells expressing C-terminal mutant S100P proteins and have no effect on the numbers of focal adhesions. Recombinant wild-type S100P protein, added extracellularly to S100P-negative cells, stimulates cell migration, which is abolished by these inhibitors. The results identify at least two S100P-dependent pathways of migration, one cell surface and the other intracellularly-linked, and identify its C-terminal lysine as a target for inhibiting multiple migration-promoting activities of S100P protein and S100P-driven metastasis.
Risk and Resilience: How Is the Health of Older Adults and Immigrant People Living in Canada Impacted by Climate- and Air Pollution-Related Exposures?

Background: In the rapidly shifting Canadian climate, an ageing population, and increased migration, a greater understanding of how local climate and air pollution hazards impact older adults and immigrant populations will be necessary for mitigating and adapting to adverse health impacts. Objectives: To explore the reported health impacts of climate change and air pollution exposures in older adults and immigrant people living in Canada, identify known factors influencing risk and resilience in these populations and gaps in the literature. Methods: We searched for research focused on older adults and immigrants living in Canada, published from 2010 onward, where the primary exposures were related to climate or air pollution. We extracted data on setting, exposures, health outcomes, and other relevant contextual factors. Results and Discussion: We identified 52 eligible studies, most focused in Ontario and Quebec. Older people in Canada experience health risks due to climate and air pollution exposures. The extent of the risk depends on multiple factors. We found little information about the climate- and air pollution-related health impacts experienced by immigrant communities. Conclusions: Further research about climate- and air pollution-related exposures, health, and which factors promote or reduce resiliency in Canada’s older adults and immigrant communities is necessary.
The Impact of Formal School Entry on Children’s Social Relationships with Parents, Siblings, and Friends

The normative transition to formal schooling confronts children with social challenges but also opportunities. Longitudinal research on how school entry impacts children’s family and friend-ship relationships is scarce. This study investigated social relationship qualities with parents, siblings, and friends among 1110 children (49.9% female) from the prospective, population-based Bavarian Longitudinal Study at 6 years (before school entry) and 8 years using a forced-choice card-sorting task. Multivariate analyses of variance revealed significant effects of age (i.e., school entry) on social relationship qualities with mothers (Pillai’s Trace (PT) = 0.28, F(9, 1101) = 47.73, p < 0.001), fathers (PT = 0.14, F(9, 1101) = 19.47, p < 0.001), siblings (PT = 0.27, F(9, 1101) = 46.14, p < 0.001), and friends (PT = 0.21, F(9, 1101) = 32.57, p < 0.001). On average, children reported higher levels of parental comfort after school entry. Companionable qualities increased in relationships with friends, whereas sibling relationships became more conflictual from preschool to early school age. Findings provide unique insights into how social relationships develop from preschool to early school age, supporting evidence of the growing importance of friends. Conflict was predominant and increasing in sibling relationships and should be considered more in future research.
Hyaluronic Acid: A Key Ingredient in the Therapy of Inflammation

Hyaluronic acid (HA) is a natural polymer, produced endogenously by the human body, which has unique physicochemical and biological properties, exhibiting desirable biocompatibility and biodegradability. Therefore, it has been widely studied for possible applications in the area of inflammatory diseases. Although exogenous HA has been described as unable to restore or replace the properties and activities of endogenous HA, it can still provide satisfactory pain relief. This review aims to discuss the advances that have been achieved in the treatment of inflammatory diseases using hyaluronic acid as a key ingredient, essentially focusing on studies carried out between the years 2017 and 2021.
Inflammatory Bowel Disease and Patients With Mental Disorders: What Do We Know?

Inflammatory bowel disease (IBD) is a multisystemic disease with a wide range of extraintestinal manifestations in both ulcerative colitis and Crohn’s disease, while increasing evidence supports the interaction between gut and central nervous system, described as “gut-brain axis”. According to epidemiological studies, it seems that patients with IBD present more frequently with impaired mental status compared to the general population, leading to diagnostic and management problems in this group of patients. The association between IBD and mental disorders, such as dementia and autism spectrum disorders, has not been fully clarified; genetic factors and the gut-brain axis seem to be involved. The purpose of this review is to present and analyze the epidemiological data about this issue, describe the possible pathogenetic mechanisms and discuss some considerations about the management of patients with IBD and impaired mental status.
Effect of Natural Sorbents in the Diet of Fattening Pigs on Meat Quality and Suitability for Processing

Simple Summary Animal production generates emissions of gaseous pollutants to the environment. Natural sorbents are used to reduce emissions increase feed safety and reduce the impact of farms on the environment. Therefore, the aim of the study was to assess the effect of three natural sorbents added to the diet of pigs on the composition and physicochemical properties of two skeletal muscles (Longissimus lumborum and semimembranosus) of crossbred pigs. The experiment was carried out on a farm in two production cycles. The animals received feed supplemented with three different natural sorbents. The results indicate that the sorbents used in the diet of pigs have no negative effect on the physicochemical properties of meat or its use as case-ready meat or material for processing. Abstract The effect of three natural sorbents added to the diet of pigs on the composition and physicochemical properties of two skeletal muscles—the musculus Longissimus lumborum (MLL) and musculus semimembranosus (MSM) of crossbred pigs were evaluated. The experiment was carried out on a farm in two production cycles. The addition of biochar (trial 1) significantly influenced instrumental color parameters, shear force and energy, and the oxidative stability of the skeletal muscles, while the proximate composition, pH, texture, and water-holding capacity (WHC) parameters did not differ significantly between groups in either of the two muscles. Similarly, no statistical differences were noted in the proximate chemical composition, texture parameters, or WHC of the meat in trial 2. The addition of both sorbents was associated with a significantly (p ≤ 0.01) lower content of haem pigments in the MLL and MSM, which was accompanied by a significantly (p ≤ 0.05) higher lightness (L*). Moreover, the MLL muscle of the pigs had higher oxidative stability, as well as lower drip loss (DL). In turn, the MSM of pigs had a significantly lower pH compared to the control group, however, the ultimate pH (48 h) in all groups was within the acceptable range (5.50–5.80). Summing up, the sorbents used are a safe ingredient in the diet of pigs, however, there is a need to continue and strengthen this line of research, including the relationships linking the future production goals of pig farming and processing potential in the meat industry with current climate policy.
Long-Term Monitoring of the Antibody Response to a SARS-CoV-2 Infection

A group of 110 patients from the West Bohemian region who had been infected with COVID-19 was monitored for the purposes of this study. We focused on cases of mild or moderate COVID-19; statistically the most likely to occur. Day zero was defined as the day on which a positive PCR test was first established. The mean length of observation was 6.5 months, the maximum length 12 months. The first blood samples were taken from a smaller cohort during the 1–3 months following the first positive PCR test. We assumed that SARS-CoV-2 antibodies would be present during this period and therefore a limited number of samples were taken for the purpose of detecting antibodies. More samples were collected, starting 4 months after the first positive PCR test. A subsequent set of blood samples were drawn, mostly 6 months after the first ones. Our study confirmed the presence of total IgG SARS-CoV-2 antibodies up to 1 year after the onset of the disease. The peak of antibody production was observed in the third month after the first positive PCR test. A mathematical estimate of the median duration of antibody positivity was calculated to be 18 months from the onset of the COVID-19 infection.
d-Amino Acids and pLG72 in Alzheimer’s Disease and Schizophrenia

Numerous studies over the last several years have shown that d-amino acids, especially d-serine, have been related to brain and neurological disorders. Acknowledged neurological functions of d-amino acids include neurotransmission and learning and memory functions through modulating N-methyl-d-aspartate type glutamate receptors (NMDARs). Aberrant d-amino acids level and polymorphisms of genes related to d-amino acids metabolism are associated with neurodegenerative brain conditions. This review summarizes the roles of d-amino acids and pLG72, also known as d-amino acid oxidase activator, on two neurodegenerative disorders, schizophrenia and Alzheimer’s disease (AD). The scope includes the changes in d-amino acids levels, gene polymorphisms of G72 genomics, and the role of pLG72 on NMDARs and mitochondria in schizophrenia and AD. The clinical diagnostic value of d-amino acids and pLG72 and the therapeutic importance are also reviewed.
The Impact of Different Coping Styles on Psychological Distress during the COVID-19: The Mediating Role of Perceived Stress

The present study aimed to understand the impact of different coping methods endorsed by Chinese college students during COVID-19 through the examination of the mediating role of perceived stress. We recruited a total of 492 undergraduate students to complete an online survey from May to June 2020. The results of structural equation modeling indicated that perceived stress was a significant mediator in the association between different coping styles and psychological distress. Three coping styles, including problem-focused, adaptive emotion-focused, and maladaptive emotion-focused coping styles were all significantly correlated with psychological distress. Perceived stress significantly mediated the association between the three coping styles and psychological distress. The results indicated a full mediation model in which problem-focused coping and adaptive emotion-focused coping affected psychological distress entirely through the mediation of perceived stress. Maladaptive emotion-focused coping positively predicted perceived stress, which in turn positively predicted psychological distress through a partial mediation model. We discuss the implications of these findings and offer suggestions for future research.
Cardiac Reverse Remodelling by 2D and 3D Echocardiography in Heart Failure Patients Treated with Sacubitril/Valsartan

In terms of sacubitril/valsartan (S/V)-induced changes in heart failure with reduced ejection fraction (HFrEF) via three-dimensional (3D) transthoracic echocardiography (TTE) and S/V effects based on HF aetiology, data are lacking. We prospectively enrolled 51 HFrEF patients (24 ischaemic, 27 non-ischaemic). At baseline and at 6-month follow-up (6MFU) after S/V treatment optimisation, we assessed the N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac remodelling by two-dimensional (2D) and 3DTTE. In non-ischaemic patients, 2D and 3DTTE showed an improvement in left ventricular (LV) size and biventricular function at 6MFU vs. baseline: 3D-LV end-diastolic volume (EDV) 103 ± 30 vs. 125 ± 32 mL/m2 (p < 0.05), 3D-LV ejection fraction (EF) 40 ± 9 vs. 32 ± 5% (p < 0.05), right ventricular (RV) 3D-EF 48.4 ± 6.5 vs. 44.3 ± 7.5% (p < 0.05); only the 3D method detected RV size reduction: 3D-RVEDV 63 ± 27 vs. 71 ± 30 mL/m2 (p < 0.05). In ischaemic patients, only 3DTTE showed biventricular size and LV function improvement: 3D-LVEDV 112 ± 29 vs. 121 ± 27 mL/m2 (p < 0.05), 3D-LVEF 35 ± 6 vs. 32 ± 5% (p < 0.05), 3D-RVEDV 57 ± 11 vs. 63 ± 14 mL/m2 (p < 0.05); RV function did not ameliorate. In both ischaemic and non-ischaemic patients, diastolic function and NT-proBNP significantly improved. In HFrEF patients treated with S/V, 3DTTE helps to ascertain subtle changes in heart chambers’ size and function, which have a major impact on HFrEF prognosis. S/V has significantly different effects on LV function in non-ischaemic vs. ischaemic patients.
Cochlear Inflammaging in Relation to Ion Channels and Mitochondrial Functions

The slow accumulation of inflammatory biomarker levels in the body—also known as inflammaging—has been linked to a myriad of age-related diseases. Some of these include neurodegenerative conditions such as Parkinson’s disease, obesity, type II diabetes, cardiovascular disease, and many others. Though a direct correlation has not been established, research connecting age-related hearing loss (ARHL)—the number one communication disorder and one of the most prevalent neurodegenerative diseases of our aged population—and inflammaging has gained interest. Research, thus far, has found that inflammatory markers, such as IL-6 and white blood cells, are associated with ARHL in humans and animals. Moreover, studies investigating ion channels and mitochondrial involvement have shown promising relationships between their functions and inflammaging in the cochlea. In this review, we summarize key findings in inflammaging within the auditory system, the involvement of ion channels and mitochondrial functions, and lastly discuss potential treatment options focusing on controlling inflammation as we age.