Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulated Microgravity Suppresses Osteogenic Differentiation of Mesenchymal Stem Cells by Inhibiting Oxidative Phosphorylation

Studies showed that energy metabolism plays a pivotal role in the differentiation of stem cells. Previous studies revealed that simulated microgravity (SMG) inhibits osteogenic differentiation of mesenchymal stem cells (MSCs). However, the underlying relationship between osteogenesis and energy metabolism under SMG conditions is not fully understood. In the present study, we investigated mitochondrial oxidative phosphorylation (OXPHOS) by assessing the level of peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α), mitochondrial DNA (mtDNA) copy number, mitochondrial mass and oxygen consumption rate (OCR) during osteogenesis of MSCs under SMG conditions. We found that SMG inhibited osteogenic differentiation and OXPHOS of MSCs. Moreover, the expression of sirtuin 1 (Sirt1), an important energy sensor, significantly decreased. After upregulating the expression of Sirt1 using resveratrol, an activator of Sirt1, SMG-inhibited OXPHOS and osteogenic differentiation of MSCs were recovered. Taken together, our results suggest that SMG suppresses osteogenic differentiation of MSCs by inhibiting OXPHOS, indicating that OXPHOS might serve as a potential therapeutic target for repairing bone loss under microgravity conditions.
Glycemic Variability and CNS Inflammation: Reviewing the Connection

Glucose is the primary energy source for the brain, and exposure to both high and low levels of glucose has been associated with numerous adverse central nervous system (CNS) outcomes. While a large body of work has highlighted the impact of hyperglycemia on peripheral and central measures of oxidative stress, cognitive deficits, and vascular complications in Type 1 and Type 2 diabetes, there is growing evidence that glycemic variability significantly drives increased oxidative stress, leading to neuroinflammation and cognitive dysfunction. In this review, the latest data on the impact of glycemic variability on brain function and neuroinflammation will be presented. Because high levels of oxidative stress have been linked to dysfunction of the blood–brain barrier (BBB), special emphasis will be placed on studies investigating the impact of glycemic variability on endothelial and vascular inflammation. The latest clinical and preclinical/in vitro data will be reviewed, and clinical/therapeutic implications will be discussed.
Primary care management of allergic rhinitis: a cross-sectional study in four ASEAN countries

Background In primary care, general practitioners (GPs) and pharmacists are tasked with the frontline responsibility of identifying and managing allergic rhinitis (AR) patients. There are currently no consolidated data on current treatment practices, patient compliance, and usage of guidelines within Southeast Asian Nations (ASEAN). Objective: To assess the attitudes and practices on AR of GPs and pharmacists in 4 ASEAN countries (Philippines, Indonesia, Thailand, and Malaysia). Methods A cross-sectional survey of 329 GPs and 548 pharmacists was conducted from May to November 2019. Participants answered a questionnaire focused on their i) current practice in the management of AR, ii) views on patient compliance, iii) understanding and usage of guidelines. Results Clinical history was the most preferred method to diagnose AR by 95.4% of GPs and 58.8% of pharmacists. Second-generation antihistamines were the most widely available treatment option in GP clinics and pharmacies (94.8% and 97.2%) and correspondingly the most preferred treatment for both mild (90.3%, 76.8%) to moderatesevere rhinitis (90.3%, 78.6%) by GPs and pharmacists, respectively. Loratadine was ranked as the most preferred 2nd generation antihistamines (GP vs pharmacists: 55.3% vs 58.9%). More than 90% of GPs and pharmacists ranked length and efficacy of treatment as important factors that increase patient compliance. Awareness of the ARIA guidelines was high among GPs (80%) and lower among pharmacists (48.4%). However, only 63.3% of GPs and 48.2% of pharmacists knew how to identify AR patients. Conclusions The survey in the 4 ASEAN countries has identified a need to strengthen the awareness and use of ARIA guidelines among the primary care practitioners. Adherence to ARIA guidelines, choosing the appropriate treatment option and prioritizing factors that increases patient compliance may contribute to better management outcomes of AR at the primary care practice
Evaluating the Effects of Grain of Isogenic Wheat Lines Differing in the Content of Anthocyanins in Mouse Models of Neurodegenerative Disorders

Functional foods enriched with plant polyphenols and anthocyanins in particular attract special attention due to multiple beneficial bioactive properties of the latter. We evaluated the effects of a grain diet rich in anthocyanins in a mouse model of Alzheimer’s disease induced by amyloid-beta (Aβ) and a transgenic mouse model of Parkinson’s disease (PD) with overexpression of human alpha-synuclein. The mice were kept at a diet that consisted of the wheat grain of near isogenic lines differing in anthocyanin content for five–six months. The anthocyanin-rich diet was safe and possessed positive effects on cognitive function. Anthocyanins prevented deficits in working memory induced by Aβ or a long-term grain mono-diet; they partially reversed episodic memory alterations. Both types of grain diets prolonged memory extinction and rescued its facilitation in the PD model. The dynamics of the extinction in the group fed with the anthocyanin-rich wheat was closer to that in a group of wild-type mice given standard chow. The anthocyanin-rich diet reduced alpha-synuclein accumulation and modulated microglial response in the brain of the transgenic mice including the elevated expression of arginase1 that marks M2 microglia. Thus, anthocyanin-rich wheat is suggested as a promising source of functional nutrition at the early stages of neurodegenerative disorders.
Retrospective Study on the Occurrence of Antibodies against Coxiella burnetii in Dogs from Central Italy

Coxiella burnetii, a cause of infection in humans and several animal species, is transmitted through inhalations and oral route but also tick bites. Its spreading in ruminants has been largely investigated, whereas data about the occurrence of this infection in canine population are scanty. In this retrospective study, blood serum samples of 516 dogs were tested by indirect immunofluorescence assay to detect antibodies against C. burnetii; 42 (8.13%) were positive with titers ranging from 1:64 to 1:512. The highest seroprevalences were detected in dogs aged > 5 years, employed in hunting activity and living in a peri-urban/rural environment. Diagnosis for C. burnetii infection should be always carried out in bitches with reproductive disorders. Moreover, in view of the zoonotic impact of this infection, asymptomatic dogs exposed to ticks’ bites and/or to contact with infected farm animals should be checked, too.
Changes in the Tumor Immune Microenvironment during Disease Progression in Patients with Ovarian Cancer

Simple Summary Immunotherapy has been a successful treatment for many cancers. However, no immunotherapy treatment has been approved for ovarian cancer due to low efficacy in this patient group. This study investigated the cellular and molecular changes from primary ovarian tumors, at the time of diagnosis, to recurrence, where the disease returns after surgery and chemotherapies. Here we examined the immune contexture to better understand subdued responses to immunotherapy and identify additional, potentially complimentary, therapeutic targets. Indications of the development of adaptive immune resistance during disease progression were observed, with increases in immune and stromal cell infiltration accompanied by the expression of immune suppressive markers. We observed high gene expression of the immune checkpoint genes LAG3 and HAVCR2 (TIM3) in most tumors and increased expression of the immune checkpoint genes TIGIT and CTLA4 in recurrent tumors, compared to the primaries. These markers may be potential candidates for immunotherapy targeting in ovarian cancer. Abstract Anti-PD1/PDL1 therapy has proven efficacious against many cancers but only reached modest objective response rates against recurrent ovarian cancer. A deeper understanding of the tumor microenvironment (TME) may reveal other immunosuppressive mechanisms that warrant investigation as immunotherapeutic targets for this challenging disease. Matched primary and recurrent tumors from patients with high-grade serous ovarian carcinoma (HGSC) were analyzed by multicolor immunohistochemistry/immunofluorescence for the presence of T cells, B cells, macrophages, and for the expression of immunosuppressive and HLA molecules. Cancer- and immune-related gene expression was assessed by NanoString analysis. Recurrent tumors showed increased infiltration by immune cells, displayed higher expression of PDL1, IDO, and HLA molecules, and contained more stromal tissue. NanoString analysis demonstrated increased expression of gene signatures related to chemokines and T cell functions in recurrent tumors. The ovarian tumors showed high gene expression of LAG3 and HAVCR2 (TIM3) and enhanced levels of TIGIT and CTLA4 in recurrent tumors compared to primary tumors. The majority of HGSC developed into a more inflamed phenotype during progression from primary to recurrent disease, including indications of adaptive immune resistance. This suggests that recurrent tumors may be particularly sensitive to inhibition of adaptive immune resistance mechanisms.
Assessing the Coloration of Coastal-Zone Waters by Digital Methods

This paper presents the results of a study of the mechanisms by which the color of coastal waters is formed on the basis of numerical simulation of the influence on the spectral distribution of ascending brightness of light (outgoing radiation) exerted by absorption, elastic scattering, inelastic (Raman) scattering in a water column, and fluorescence of chlorophyll (Chl) and dissolved organic matter (DOM), as well as the optical interaction of light photons with the bottom of a water body. The authors demonstrate that the radiometric characteristics of water color perceived by an observer from above may experience considerable changes, depending on the nature of bottom cover (ooze, vegetation), the depths at which the bottom occurs, the geometry of water surface illumination by sunlight, and the concentrations of such substances as chlorophyll, suspended mineral matter (SMS), and dissolved organic matter.
Antimicrobial Peptides in Farm Animals: An Updated Review on Its Diversity, Function, Modes of Action and Therapeutic Prospects

Antimicrobial peptides (AMPs) are the arsenals of the innate host defense system, exhibiting evolutionarily conserved characteristics that are present in practically all forms of life. Recent years have witnessed the emergence of antibiotic-resistant bacteria compounded with a slow discovery rate for new antibiotics that have necessitated scientific efforts to search for alternatives to antibiotics. Research on the identification of AMPs has generated very encouraging evidence that they curb infectious pathologies and are also useful as novel biologics to function as immunotherapeutic agents. Being innate, they exhibit the least cytotoxicity to the host and exerts a wide spectrum of biological activity including low resistance among microbes and increased wound healing actions. Notably, in veterinary science, the constant practice of massive doses of antibiotics with inappropriate withdrawal programs led to a high risk of livestock-associated antimicrobial resistance. Therefore, the world faces tremendous pressure for designing and devising strategies to mitigate the use of antibiotics in animals and keep it safe for posterity. In this review, we illustrate the diversity of farm animal-specific AMPs, and their biochemical foundations, mode of action, and prospective application in clinics. Subsequently, we present the data for their systematic classification under the major and minor groups, antipathogenic action, and allied bioactivities in the host. Finally, we address the limitations of their clinical implementation and envision areas for further advancement.
Monoclonal Gammopathy of Renal Significance with Deposits of Peculiar Morphology and Injuries of Secondary Thrombotic Microangiopathy: A Case Report and Review of the Literature

We present the case of an 82-year-old woman diagnosed with monoclonal gammopathy of renal significance (MGRS) with the presence of different and peculiar kidney lesions, who began treatment with bortezomib and dexamethasone, presenting during her evolution a relapse. Although the bone marrow biopsy in this case showed plasma cells as pathologic clone and there was also a reduction after chemotherapeutic treatment, rituximab was proposed as a second line. We suspected that the relapse was possibly due to another precursor as B-cell or lymphoplasmacytic cell clone. We review the literature and suggest that the treatment for MGRS should be patient-tailored, preferably by consulting a multidisciplinary team. Future research is needed to better understand the disease course and establish the efficacy and safety of the therapeutic approach for the relapse of MGRS.
hsa_circRNA_000166 Facilitated Cell Growth and Limited Apoptosis through Targeting miR-326/LASP1 Axis in Colorectal Cancer

Circular RNAs (circRNAs) belong to noncoding RNAs and are widely expressed in a variety of cell species, including cancers. However, the function and mechanism of circRNAs in colorectal cancer (CRC) has not been well investigated. Here, we firstly downloaded and analyzed the circRNA expression profile of CRC from the Gene Expression Omnibus (GEO) database. And we identified 181 differentially expressed circRNAs between 10 pairs of CRC and adjacent normal tissues. Interestingly, we observed that the expression of hsa_circRNA_000166 was the top increased among these circRNAs. Then, we confirmed an upregulation of hsa_circRNA_000166 in CRC tissues and cell lines and observed that higher expression of hsa_circRNA_000166 was associated with poor 5-year survival rate of patients with CRC. Next, we investigated the function of hsa_circRNA_000166 during CRC progression by knocking down its expression. Cell growth and apoptosis assay revealed that hsa_circRNA_000166 regulated the cell growth and apoptosis in CRC cell lines. Furthermore, we identified that hsa_circRNA_000166 targeted the miR-326/LASP1 pathway using bioinformatics analysis and luciferase reporter assay. Finally, suppression of miR-326 or overexpression of LASP1 could sufficiently rescue the aberrant cell growth and apoptosis in CRC cell lines. Taken together, our results indicated that downregulation of hsa_circRNA_000166 inhibited the cell growth and facilitated apoptosis during CRC development by sponging the miR-326/LASP1 pathway.
What Open-Lung Biopsy Teaches Us about ARDS in COVID-19 Patients: Mechanisms, Pathology, and Therapeutic Implications

Difficulties have risen while managing Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19, although it meets the Berlin definition. Severe hypoxemia with near-normal compliance was noted along with coagulopathy. Understanding the precise pathophysiology of this atypical ARDS will assist researchers and physicians in improving their therapeutic approach. Previous work is limited to postmortem studies, while our report addresses patients under protective lung mechanical ventilation. An open-lung minithoracotomy was performed in 3 patients who developed ARDS related to COVID-19 and were admitted to the intensive care unit to carry out a pathological and microbiological analysis on lung tissue biopsy. Diffused alveolar damage with hyaline membranes was found, as well as plurifocal fibrin microthrombi and vascular congestion in all patients' specimens. Microbiological cultures were negative, whereas qualitative Reversed Transcriptase Polymerase Chain Reaction (RT-PCR) detected SARS-CoV-2 in the pulmonary parenchyma and pleural fluid in two patients. COVID-19 causes progressive ARDS with onset of severe hypoxemia, underlying a dual mechanism: shunt effect through diffused alveolar damage and dead space effect through thrombotic injuries in microvascular beds. It seems reasonable to manage this ventilation-perfusion ratio mismatch using a high dose of anticoagulant combined with glucocorticoids.
Differential Response of Mycorrhizal Plants to Tomato bushy stunt virus and Tomato mosaic virus Infection

Tomato bushy stunt virus (TBSV) and Tomato mosaic virus (ToMV) are important economic pathogens in tomato fields. Rhizoglomus irregulare is a species of arbuscular mycorrhizal (AM) fungus that provides nutrients to host plants. To understand the effect of R. irregulare on the infection by TBSV/ToMV in tomato plants, in a completely randomized design, five treatments, including uninfected control plants without AM fungi (C), uninfected control plants with AM fungi (M) TBSV/ToMV-infected plants without AM fungi (V), TBSV/ToMV-infected plants before mycorrhiza (VM) inoculation, and inoculated plants with mycorrhiza before TBSV/ToMV infection (MV), were studied. Factors including viral RNA accumulation and expression of Pathogenesis Related proteins (PR) coding genes including PR1, PR2, and PR3 in the young leaves were measured. For TBSV, a lower level of virus accumulation and a higher expression of PR genes in MV plants were observed compared to V and VM plants. In contrast, for ToMV, a higher level of virus accumulation and a lower expression of PR genes in MV plants were observed as compared to V and VM plants. These results indicated that mycorrhizal symbiosis reduces or increases the viral accumulation possibly via the regulation of PR genes in tomato plants.
SARS-CoV-2 Seroprevalence Survey in People Involved in Different Essential Activities during the General Lock-Down Phase in the Province of Prato (Tuscany, Italy)

Serosurveys may help to assess the transmission dynamics in high-risk groups. The aim of the study was to assess the SARS-CoV-2 antibody seroprevalence in people who had performed essential activities during the lock-down period in the Province of Prato (Italy), and to evaluate the risk of exposure to SARS-CoV-2 according to the type of service. All the workers and volunteers of the Civil Protection, employees of the municipalities, and all the staff of the Health Authority of the Province of Prato were invited to be tested with a rapid serological test. A total of 4656 participants were tested. SARS-CoV-2 antibodies were found in 138 (2.96%) cases. The seroprevalence in health care workers, in participants involved in essential support services and in those who worked from home were 4.1%, 1.4% and 1.0%, respectively. Health care workers experienced higher odds of seropositivity (OR 4.38, 95%CI 2.19–10.41) than participants who were assigned to work-from-home; no significant seropositivity differences were observed between support services and work-from-home groups. A low circulation of SARS-CoV-2 was observed among participants performing different essential activities. Findings highlighted the risk of in-hospital transmission in healthcare workers and that community support services may increase the risk of seropositivity to a limited extent in low incidence areas.
Quality of Working Life, Psychosocial Factors, Burnout Syndrome and Emotional Intelligence

The objective of this work is to study the quality of working life associated to psychosocial factors and risks, burnout syndrome and emotional intelligence, as well as being able to detect predictors of the said syndrome. The sample consisted of 311 professionals working in direct contact with an intellectual disability from 15 associations of Extremadura (Spain). The Spanish version of the CESQT questionnaire was administered to evaluate burnout syndrome, the Wong & Law Emotional Intelligence Scale (WLEIS) was used to evaluate emotional intelligence, while the UNIPSICO Battery was used to evaluate the psychosocial factors of demands (work–family conflict and psychosomatic problems) and resources, such as social support and work satisfaction. The results indicate average values of burnout, revealing that work satisfaction, emotional intelligence, and social support are related to burnout syndrome. In addition, there are also positive correlations between psychosomatic symptoms and work–family conflict. Satisfaction at work, social support, and emotional intelligence (intrapersonal and interpersonal perception, use and regulation of emotions) predict burnout syndrome. What is more, the psychosomatic symptoms and work–family conflict explain, respectively, 17% and 17.9% of their variance. Thus, there is a need to develop intervention programs that encourage social support and the conciliation of family life, as well as training skills related to emotional intelligence, such as communication and conflict resolution.
Current Developments in the Epidemiology and Control of Enzootic Bovine Leukosis as Caused by Bovine Leukemia Virus

Enzootic Bovine Leukosis (EBL) caused by the bovine leukemia virus (BLV) has been eradicated in over 20 countries. In contrast, the U.S. and many other nations are experiencing increasing prevalence in the absence of efforts to control transmission. Recent studies have shown that BLV infection in dairy cattle has a greater impact beyond the long-recognized lymphoma development that occurs in <5% of infected cattle. Like other retroviruses, BLV appears to cause multiple immune system disruptions, affecting both cellular and humoral immunity, which are likely responsible for increasingly documented associations with decreased dairy production and decreased productive lifespan. Realization of these economic losses has increased interest in controlling BLV using technology that was unavailable decades ago, when many nations eradicated BLV via traditional antibody testing and slaughter methods. This traditional control is not economically feasible for many nations where the average herd antibody prevalence is rapidly approaching 50%. The ELISA screening of cattle with follow-up testing via qPCR for proviral load helps prioritize the most infectious cattle for segregation or culling. The efficacy of this approach has been demonstrated in at least four herds. Breeding cattle for resistance to BLV disease progression also appears to hold promise, and several laboratories are working on BLV vaccines. There are many research priorities for a wide variety of disciplines, especially including the need to investigate the reports linking BLV and human breast cancer.