Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxidative Stress in ESRD Patients on Dialysis and the Risk of Cardiovascular Diseases

Chronic kidney disease is highly prevalent worldwide. The decline of renal function is associated with inadequate removal of a variety of uremic toxins that exert detrimental effects on cells functioning, thus affecting the cardiovascular system. The occurrence of cardiovascular aberrations in CKD is related to the impact of traditional risk factors and non-traditional CKD-associated risk factors, including anemia; inflammation; oxidative stress; the presence of some uremic toxins; and factors related to the type, frequency of dialysis and the composition of dialysis fluid. Cardiovascular diseases are the most frequent cause for the deaths of patients with all stages of renal failure. The kidney is one of the vital sources of antioxidant enzymes, therefore, the impairment of this organ is associated with decreased levels of these enzymes as well as increased levels of pro-oxidants. Uremic toxins have been shown to play a vital role in the onset of oxidative stress. Hemodialysis itself also enhances oxidative stress. Elevated oxidative stress has been demonstrated to be strictly related to kidney and cardiac damage as it aggravates kidney dysfunction and induces cardiac hypertrophy. Antioxidant therapies may prove to be beneficial since they can decrease oxidative stress, reduce uremic cardiovascular toxicity and improve survival.
Evaluation of lipid profile, antioxidant and immunity statuses of rabbits fed Moringa oleifera leaves.

Objective The present study aimed to investigate the effect of Moringa oleifera leaves (MOL) on blood hematology, lipid profile and immunity status of growing rabbits. Methods A total of 120, unsexed Alexandria line weaned rabbits, at 4 weeks of age were randomly divided into four groups (30 rabbits each). The first group was fed the control diet and the other groups (2-4) were fed the basal diet supplemented with 10, 20 or 30% MOL for 5 weeks of experimental period. Results Data revealed that dietary supplementation with 20% MOL recorded the significantly highest live body weight and increased hemoglobin and packed cell volume at 9 weeks of age compared to other groups. Increasing Moringa levels resulted in a significant increase in white blood cells, lymphocytes, globulin and high density lipoprotein, total antioxidant capacity, Immunoglobulin G and M levels compared to control, but, total lipids, cholesterol, malondialdehyde and liver glycogen values decreased significantly. With 20% MOL thymus histology showed an outer cortex of small lymphocytes, heavily- stained densely- packed lymphocytes surrounding the inner marrow clear pale medulla in contrast with other groups. Conclusion It can be concluded that 20% Moringa leaves may exert beneficial effects on lipid, antioxidant and immune status properties of growing rabbits.
Not so much rational but rationalizing: Humans evolved as coherence-seeking, fiction-making animals.

The evidence for biased perceptions and judgments in humans coupled with evidence for ecological rationality in nonhuman animals suggest that the claim that humans are the rational animal may be overstated. We instead propose that discussions of human psychology may benefit from viewing ourselves not so much as rational animals but rather as the rationalizing animal. The current article provides evidence that rationalization is unique to humans and argues that rationalization processes (e.g., cognitive dissonance reduction, post hoc justification of choices, confabulation of reasons for moral positions) are aimed at creating the fictions we prefer to believe and maintaining the impression that we are psychologically coherent and rational. Coherence appears to be prioritized at the expense of veridicality, suggesting that distorted perceptions and appraisals can be adaptive for humans-under certain circumstances, we are better off understanding ourselves and reality not so accurately. Rationalization also underlies the various shared beliefs, religions, norms, and ideologies that have enabled humans to organize and coordinate their actions on a grand scale, for better or worse. We conclude with a discussion of the implications of this unique human psychological trait. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Neurite Orientation Dispersion and Density Imaging for Assessing Acute Inflammation and Lesion Evolution in MS

Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. Twenty-one subjects with MS underwent serial enhanced MRIs including NODDI, the key metrics of which are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase. BACKGROUND AND PURPOSE: MR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations. MATERIALS AND METHODS: Twenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM. RESULTS: The orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions. CONCLUSIONS: NODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.
Antioxidant and modulatory properties of kernel flour extracts of three Nigerian local mango varieties on enzymes relevant to metabolic syndrome

Aim: Recent studies have shown that flour of mango kernel is a rich natural source of biologically active phytochemicals with important health benefits, such as phenolic compounds. Hence, this study evaluated antioxidant and modulatory properties of methanol extracts of kernel flours of three Nigerian local mango varieties (Sherri, Ogbomoso and Elemi) on some enzymes relevant to the development of metabolic syndrome (MS). Methods: Enzymes [pancreatic lipase (PL), α-amylase, α-glucosidase, angiotensin I-converting enzyme (ACE) and xanthine oxidase (XO)] inhibitory assays, antioxidant activities and antioxidant phytochemicals contents of extracts were carried out using spectrophotometer. Results: All the three mango varieties strongly inhibited PL, α-amylase, α-glucosidase, ACE and XO. Generally, Elemi had the strongest inhibitory effect on the enzymes, followed by Sherri and Ogbomoso. It also had the highest total phenols, total flavonoids, tannins and total saponins contents, and displayed the strongest ABTS*+ and DPPH* scavenging activities and reducing power, compared with Sherri and Ogbomoso. Conclusions: By inhibiting PL, α-amylase, α-glucosidase, ACE and XO, kernel flour extracts of the three Nigerian local mango varieties may be beneficial for retarding the production of fatty acids, glucose, angiotensin II and uric acid, representing an important approach for managing obesity, T2D, hypertension and hyperuricemia, respectively. The mango kernel flours, especially Elemi, may therefore be harnessed to develop low-cost nutraceuticals for managing metabolic syndrome.
Protein disulfide isomerase is regulated in multiple ways: Consequences for conformation, activities, and pathophysiological functions

Protein disulfide isomerase (PDI) is one of the most abundant and critical protein folding catalysts in the endoplasmic reticulum of eukaryotic cells. PDI consists of four thioredoxin domains and interacts with a wide range of substrate and partner proteins due to its intrinsic conformational flexibility. PDI plays multifunctional roles in a variety of pathophysiological events, both as an oxidoreductase and a molecular chaperone. Recent studies have revealed that the conformation and activity of PDI can be regulated in multiple ways, including posttranslational modification and substrate/ligand binding. Here, we summarize recent advances in understanding the function and regulation of PDI in different pathological and physiological events. We propose that the multifunctional roles of PDI are regulated by multiple mechanisms. Furthermore, we discuss future directions for the study of PDI, emphasizing how different regulatory modes are linked to the conformational changes and biological functions of PDI in the context of diverse pathophysiologies.
Different Role of Raptor and Rictor in Regulating Rasfonin‐Induced Autophagy and Apoptosis in Renal Carcinoma Cells

Both Raptor and Rictor are the key components in the complexes of mammalian target of rapamycin (mTOR), which play a vital role in mediating autophagy. Unlike mTOR, the regulatory role of either Raptor or Rictor in the regulation of autophagic process is relatively less explored. In present study, we found that rasfonin, which isolated from Talaromyces sp. 3656‐A1 and was a fungal natural product, activated both caspase‐dependent apoptosis and autophagy in ACHN, a renal carcinoma cell line. Knockdown of Raptor decreased both rasfonin‐induced autophagic flux and PARP‐1 cleavage, and in contrast, Rictor silencing increased apoptosis concomitantly enhancing rasfonin‐induced autophagy. Unexpectedly, API‐2, which was widely used as an inhibitor of Akt, promoted rasfonin‐dependent autophagy in Raptor‐depleted but not Rictor‐deprived cells. Collectively, these results demonstrated that Raptor and Rictor could play a distinctly regulatory role in rasfonin‐enhanced autophagy and apoptosis.
Physical Therapist Management of COVID-19 in the Intensive Care Unit: The West China Hospital Experience

Abstract Objective Coronavirus disease 2019 (COVID-19) has dominated the attention of health care systems globally since January 2020. Various health disciplines including physical therapists are still exploring the best way to manage this new disease. The role and involvement of physical therapists in the management of COVID-19 are not yet well defined and are limited in many hospitals. This article reports a physical therapy service specially commissioned by the Health Commission of Sichuan Province to manage COVID-19 during patients’ stay in the intensive care unit (ICU) at the Public Health Clinical Center of Chengdu in China. Methods Patients diagnosed with COVID-19 were classified into 4 categories under a directive from the National Health Commission of the People’s Republic of China. Patients in the “severe” and “critical” categories were admitted to the ICU irrespective whether mechanical ventilation was required. Between January 31, 2020, and March 8, 2020, a cohort of 16 patients was admitted to the ICU at the Public Health Clinical Center of Chengdu. The median (minimum to maximum) hospital and ICU stays for these patients were 27 (11–46) and 15 (6–38) days, respectively. Medical management included antiviral, immunoregulation and supportive treatment of associated comorbidities. Physical therapist interventions included body positioning, airway clearance techniques, oscillatory positive end-expiratory pressure, inspiratory muscle training, and mobility exercises. All patients had at least 1 comorbidity. Three of the 16 patients required mechanical ventilation and were excluded for outcome measures that required understanding of verbal instructions. In the remaining 13 patients, respiratory outcomes—including the Borg Dyspnea Scale, peak expiratory flow rate, Pao2/Fio2 ratio, maximal inspiratory pressure, strength outcomes, Medical Research Council Sum Score, and functional outcomes (including the Physical Function in Intensive Care Test score, De Morton Mobility Index, and Modified Barthel Index)—were measured on the first day the patient received the physical therapist intervention and at discharge. Results At discharge from the ICU, while most outcome measures were near normal for the majority of the patients, 61% and 31% of these patients had peak expiratory flow rate and maximal inspiratory pressure below 80% of the predicted value and 46% had De Morton Mobility Index values below the normative value. Conclusion The respiratory and physical functions of some patients remained poor at ICU discharge, suggesting that long-term rehabilitation may be required for these patients. Impact Our experience in the management of patients with COVID-19 has revealed that physical therapist intervention is safe and appears to be associated with an improvement in respiratory and physical function in patients with COVID-19 in the ICU.
Caution in interpretation of abnormal carbon monoxide diffusion capacity in COVID-19 patients

We read with much interest the recent findings published in the European Respiratory Journal of reduced gas transfer in patients following coronavirus disease 2019 (COVID-19). Mo et al. [1] investigated conventional pulmonary function in survivors of mild, moderate and severe COVID-19 approximately 20–30 days after onset of symptoms. While patients had relatively normal spirometry, diffusing capacity of the lung for carbon monoxide (DLCO) was reduced in 50% and DLCO/alveolar volume (VA) (or KCO, to avoid misinterpretation) reduced in 25%. These findings are welcome as they provide significant insight into the long-term lung function impairment associated with COVID-19. Reduced KCO in discharged patients with COVID-19 suggests persistent abnormalities in gas exchange. Further research is required to understand why. https://bit.ly/2Hb00gq
Lactate in the Tumor Microenvironment: An Essential Molecule in Cancer Progression and Treatment

Simple Summary The role of lactate in cancer described by Otto Warburg in 1927 states that cancer cells uptake high amount of glucose with a marked increase in lactate production, this is known as the “Warburg effect”. Since then lactate turn out to be a major signaling molecule in cancer progression. Its release from tumor cells is accompanied by acidification ranging from 6.3 to 6.9 in the tumor microenvironment (TME) which favors processes such as tumor promotion, angiogenesis, metastasis, tumor resistance and more importantly, immunosuppression which has been associated with a poor outcome. The goal of this review is to examine and discuss in deep detail the recent studies that address the role of lactate in all these cancerous processes. Lastly, we explore the efforts to target the lactate production and its transport as a promising approach for cancer therapeutics. Abstract Cancer is a complex disease that includes the reprogramming of metabolic pathways by malignant proliferating cells, including those affecting the tumor microenvironment (TME). The “TME concept” was introduced in recognition of the roles played by factors other than tumor cells in cancer progression. In response to the hypoxic or semi-hypoxic characteristic of the TME, cancer cells generate a large amount of lactate via the metabolism of glucose and glutamine. Export of this newly generated lactate by the tumor cells together with H+ prevents intracellular acidification but acidifies the TME. In recent years, the importance of lactate and acidosis in carcinogenesis has gained increasing attention, including the role of lactate as a tumor-promoting metabolite. Here we review the existing literature on lactate metabolism in tumor cells and the ability of extracellular lactate to direct the metabolic reprogramming of those cells. Studies demonstrating the roles of lactate in biological processes that drive or sustain carcinogenesis (tumor promotion, angiogenesis, metastasis and tumor resistance) and lactate’s role as an immunosuppressor that contributes to tumor evasion are also considered. Finally, we consider recent therapeutic efforts using available drugs directed at and interfering with lactate production and transport in cancer treatment.
BRAF Mutation in Colorectal Cancers: From Prognostic Marker to Targetable Mutation

Simple Summary Colorectal cancer with a mutation in an oncogene BRAF has paid much attention, as it comprises a population with dismal prognosis since two decades ago. A series of research since then has successfully changed this malignancy to be treatable with specific treatment. Here we thoroughly overviewed the basic, translational and clinical studies on colorectal cancer with BRAF mutation from a physician’s viewpoint. Accumulating lines of evidence suggest that intervention of the trunk cellular growth signal transduction pathway, namely EGFR-RAS-RAF-MEK-ERK pathway, is a clue to controlling this disease. However, it is not so straightforward. Recent studies unveil the diverse and plastic nature of this signal transduction pathway. We will introduce our endeavor to conquer this condition, based on newly arriving datasets, and discuss how we could open the door to future development of CRC treatment. Abstract The Raf murine sarcoma viral oncogene homolog B (BRAF) mutation is detected in 8–12% of metastatic colorectal cancers (mCRCs) and is strongly correlated with poor prognosis. The recent success of the BEACON CRC study and the development of targeted therapy have led to the determination of BRAF-mutated mCRCs as an independent category. For nearly two decades, a growing body of evidence has established the significance of the BRAF mutation in the development of CRC. Herein, we overview both basic and clinical data relevant to BRAF-mutated CRC, mainly focusing on the development of treatment strategies. This review is organized into eight sections, including clinicopathological features, molecular features, prognosis, the predictive value of anti-epidermal growth factor receptor (EGFR) therapy, resistant mechanisms for BRAF-targeting treatment, the heterogeneity of the BRAF mutation, future perspectives, and conclusions. A characterization of the canonical mitogen-activated protein kinase (MAPK) pathway is essential for controlling this malignancy, and the optimal combination of multiple interventions for treatments remains a point of debate.
Selectivity filter ion binding affinity determines inactivation in a potassium channel

Significance The role of the selectivity filter in controlling potassium channel activity is different for different channels, despite identical sequences and structures. While KcsA and voltage-gated channels experience C-type inactivation by collapsing their selectivity filters under reduced potassium concentration, the mechanism by which the MthK channel regulates gating at the filter is unclear. Unlike the KcsA selectivity filter that experiences a uniform titration of its ion binding sites, leading to collapse, high-resolution X-ray structures of the pore-only MthK channel reveal that only the central S2 site loses its ion at low concentrations, insufficient for a conformational change. The selectivity filters of MthK and KcsA differ in their ion affinities due to interactions behind the filter, determining their inactivation phenotypes. Potassium channels can become nonconducting via inactivation at a gate inside the highly conserved selectivity filter (SF) region near the extracellular side of the membrane. In certain ligand-gated channels, such as BK channels and MthK, a Ca2+-activated K+ channel from Methanobacterium thermoautotrophicum, the SF has been proposed to play a role in opening and closing rather than inactivation, although the underlying conformational changes are unknown. Using X-ray crystallography, identical conductive MthK structures were obtained in wide-ranging K+ concentrations (6 to 150 mM), unlike KcsA, whose SF collapses at low permeant ion concentrations. Surprisingly, three of the SF’s four binding sites remained almost fully occupied throughout this range, indicating high affinities (likely submillimolar), while only the central S2 site titrated, losing its ion at 6 mM, indicating low K+ affinity (∼50 mM). Molecular simulations showed that the MthK SF can also collapse in the absence of K+, similar to KcsA, but that even a single K+ binding at any of the SF sites, except S4, can rescue the conductive state. The uneven titration across binding sites differs from KcsA, where SF sites display a uniform decrease in occupancy with K+ concentration, in the low millimolar range, leading to SF collapse. We found that ions were disfavored in MthK’s S2 site due to weaker coordination by carbonyl groups, arising from different interactions with the pore helix and water behind the SF. We conclude that these differences in interactions endow the seemingly identical SFs of KcsA and MthK with strikingly different inactivating phenotypes.
Synergistic Effect of Beauveria bassiana and Trichoderma asperellum to Induce Maize (Zea mays L.) Defense against the Asian Corn Borer, Ostrinia furnacalis (Lepidoptera, Crambidae) and Larval Immune Response

Ostrinia furnacalis, is the major pest of maize causing significant yield losses. So far, many approaches have been used to increase the virulence of entomopathogenic fungal isolates. The current study is an attempt to estimate synergistic effect of Beauveria bassiana and Trichoderma asperellum in order to explore larval immune response through RNA sequencing and differentially expression analysis. In vivo synergism was examined in seven proportions (B. bassiana: T. asperellum = 1:1, 1:2, 1:3, 1:4, 4:1, 3:1, 2:1) and in the in vitro case, two inoculation methods were applied: seed coating and soil drenching. Results revealed significant decrease in plant damage and high larval mortality in fungal treatments. Fungal isolates mediated the plant defense by increasing proline, superoxide dismutase (SOD), peroxidase (POD), polyphenol oxidase (PPO) and protease activities. Seed coating method was proved to be the most effective in case of maize endophytic colonization. In total, 59 immune-related differentially expressed genes DEGs were identified including, cytochrome P450, heat shock protein, ABC transporter, cadherin, peptidoglycan recognition protein (PGRP), cuticlular protein, etc. Further, transcriptomic response was confirmed by qRT-PCR. Our results concluded that, coculture of B. bassiana and T. asperellum has the synergistic potential to suppress the immune response of O. furnacalis and can be used as sustainable approach to induce plant resistance through activation of defense-related enzymes.