Miracle-dz/UniFAR-FTUs huggingface dataset:
Estradiol Alleviates Intervertebral Disc Degeneration through Modulating the Antioxidant Enzymes and Inhibiting Autophagy in the Model of Menopause Rats

Objective To investigate the effects of menopause on redox balance in the intervertebral disc and to examine whether oxidative stress and autophagy were associated with disc degeneration in menopause rats. Methods Thirty female Sprague-Dawley rats were randomly divided into three groups (sham, ovariectomized with vehicle, and ovariectomized with estrogen). At the end of the 3-month treatment, the rats were examined by 3.0 T MRI. Serum estradiol (E2) level was measured. Redox balance of nucleus pulposus was determined by measuring total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), and oxidized glutathione (GSSG). Transmission electron microscopy (TEM), immunohistochemical staining, and Western blot were used to determine the nucleus pulposus autophagy level. At the same time, Spearman's correlation coefficient was used to describe the relationship between intervertebral disc grade, oxidative stress status, serum E2, and autophagy level. Results The level of serum E2 was significantly decreased by ovariectomy and can be corrected by the estrogen replacement therapy (ERT). In OVX rats, an increased oxidative stress and high level of autophagy were observed in nucleus pulposus tissue. ERT prevented the intervertebral disc degeneration (IVDD), restored the redox balance, and reduced autophagy level. Conclusion Ovariectomy induced oxidative stress, autophagy, and intervertebral disc degeneration. Autophagy of the intervertebral disc was negatively correlated with oxidative stress, and the level of autophagy can be reduced by ERT through modulating the redox balance and downregulating the autophagy level. Regulating the redox balance of IVD may be a potential therapeutic option for degeneration of the disc in the postmenopausal women.
Curcumin nanoparticles are a promising anti-bacterial and anti-inflammatory agent for treating periprosthetic joint infections

Background Periprosthetic joint infections (PJIs) have a high incidence of recurrence after total joint replacement and are difficult to treat by debridement or antibiotic treatment. Curcumin is a natural product with anti-inflammatory and anti-bacterial properties. The low bioactivity of curcumin in water restricts its clinical application. Curcumin nanoparticles (CURN) were developed to overcome this limitation. Methods In this study, the therapeutic effects of CURN and their anti-inflammatory functions were investigated in a Staphylococcus aureus biofilm-induced PJIs model. Results CURN first attenuated the biofilm-induced expansion of myeloid-derived suppressor cells (MDSCs) and then regulated M1- and M2-phenotypic MDSC expression. Down-regulation of cytokines and reactive oxygen species was considered as the mechanism of CURN in reversing the suppression of T cell proliferation. The recovery of bone permeative destruction demonstrated that CURN enhanced therapeutic potency of vancomycin in vivo. Conclusion This is the first study to demonstrate that CURN may be useful for treating PJIs.
Exome Sequencing–Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants

Key Points Question Can population-level genomic screening identify those at risk for disease? Findings In this cross-sectional study of an unselected population cohort of 50 726 adults who underwent exome sequencing, pathogenic and likely pathogenic BRCA1 and BRCA2 variants were found in a higher proportion of patients than was previously reported. Meaning Current methods to identify BRCA1/2 variant carriers may not be sufficient as a screening tool; population genomic screening for hereditary breast and ovarian cancer may better identify patients at high risk and provide an intervention opportunity to reduce mortality and morbidity.
Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity

Importance Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors. Objectives To determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association. Design, Setting, and Participants This prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018. Interventions and Exposures The initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden. Main Outcomes and Measures Weight, waist circumference, and hip girth were measured at baseline and at scheduled visits. Results Of the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P = .01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (−0.59 kg; 95% CI, –1.80 to 0.62 kg; P = .34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P = .02) but not the lifestyle intervention group (−0.09 cm; 95% CI, −0.82 to 0.63 cm; P = .80). No associations were observed for changes in mean waist circumference. Conclusions and Relevance Among adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals. Trial Registration ClinicalTrials.gov Identifier: NCT00004992 and NCT00038727
Changes in Influenza Vaccination Requirements for Health Care Personnel in US Hospitals

Key Points Question How has the proportion of US hospitals requiring receipt of annual influenza vaccination among health care personnel changed in recent years? Findings In this national survey study, which included responses from 1062 infection preventionists at both Veterans Affairs and non–Veterans Affairs hospitals between the 2013 and 2017 calendar years, required influenza vaccinations among health care personnel increased from 37.1% to 61.4%; this change was driven by increases in non–Veterans Affairs hospitals. Meaning Influenza vaccination mandates for health care personnel have increased in recent years, coinciding with concurrent increases in vaccination coverage among health care personnel.
Association of Electronic Cigarette Use With Smoking Habits, Demographic Factors, and Respiratory Symptoms

Key Points Question Who uses electronic cigarettes (e-cigarettes), and is there an association between e-cigarette use and respiratory symptoms? Findings In a random sample of more than 30 000 Swedish adults, e-cigarette use was most common among current smokers, and the prevalence of respiratory symptoms was highest among the current smokers who also used e-cigarettes. Meaning Longitudinal studies will be essential to further determine the long-term health effects of e-cigarette use and whether in dual users it increases the burden of respiratory conditions or encourages sustainable smoking cessation.
Racial Disparities in Patient Characteristics and Survival After Acute Myocardial Infarction

Key Points Question Does race serve as a surrogate for socioeconomic and clinical factors, and, after adjusting for those factors, do long-term mortality rates differ between black patients and white patients following acute myocardial infarction? Findings In this cohort study of 6402 patients from 2 acute myocardial infarction registries, self-identified black patients and white patients differed in several clinical and socioeconomic characteristics. The higher the prevalence of characteristics associated with being a black patient, the higher the 5-year mortality rate, but no differences were observed between black patients and white patients with similar characteristics. Meaning A greater prevalence of characteristics associated with black race, but not race itself, was associated with higher mortality risk after acute myocardial infarction.
Characteristics of Physicians Excluded From US Medicare and State Public Insurance Programs for Fraud, Health Crimes, or Unlawful Prescribing of Controlled Substances

Key Points Question What were the characteristics of physicians who have been excluded from US Medicare and state public insurance programs? Findings In this cross-sectional study assessing all physician exclusions from 2007 to 2017, the number of physician exclusions grew by 20% per year (equivalent to 48 additional exclusions per year) to encompass approximately 0.3% of US physicians in 2017. Exclusions were more common in the West and Southeast census regions, and male physicians, physicians with osteopathic training, older physicians, and physicians in specific specialties (eg, family medicine, psychiatry, internal medicine, anesthesiology, surgery, and obstetrics/gynecology) were more likely to be excluded. Meaning The likelihood of exclusion varied across regions and with physician demographics and specialty.
Association Between Autism Spectrum Disorders With or Without Intellectual Disability and Depression in Young Adulthood

Key Points Questions Are individuals with autism spectrum disorders more likely to have depression in adulthood than the general population, and do these risks have a familial basis and differ by coexisting intellectual disability? Findings In this Swedish population-based cohort study of 223 842 participants with a nested sibling comparison, individuals with autism spectrum disorders, especially those without intellectual disability, had a greater risk of a depression diagnosis in young adulthood than the general population and their nonautistic siblings. Meaning According to this study’s results, depression is overrepresented in autism spectrum disorders, and this higher risk may not be explained by shared familial liability; research identifying modifiable pathways may help develop preventive interventions.
Gegen Qinlian Decoction Attenuates High-Fat Diet-Induced Steatohepatitis in Rats via Gut Microbiota

Gut microbiota play an important role in modulating energy contribution, metabolism, and inflammation, and disruption of the microbiome population is closely associated with chronic metabolic diseases, such as nonalcoholic fatty liver disease (NAFLD). Gegen Qinlian decoction (GGQLD), a well-known traditional Chinese herbal medicine (CHM), was previously found to regulate lipid metabolism and attenuate inflammation during NAFLD pathogenesis. However, the underlying mechanism of this process, as well as how the gut microbiome is involved, remains largely unknown. In this study, we investigated the effect of varying doses of GGQLD on the total amount and distribution of gut bacteria in rats fed a high-fat diet (HFD) for 8 weeks. Our analysis indicates that Oscillibacter and Ruminococcaceae_g_unclassified are the dominant families in the HFD group. Further, HFD-dependent differences at the phylum, class, and genus levels appear to lead to dysbiosis, characterized by an increase in the Firmicutes/Bacteroidetes ratio and a dramatic increase in the Oscillibacter genus compared to the control group. Treatment with GGQLD, especially the GGQLL dose, improved these HFD-induced changes in intestinal flora, leading to increased levels of Firmicutes, Clostridia, Lactobacillus, bacilli, and Erysipelotrichales that were similar to the controls. Taken together, our data highlight the efficacy of GGQLD in treating NAFLD and support its clinical use as a treatment for NAFLD/NASH patients.
Individual and Occupational Differences in Perceived Organisational Culture of a Central Hospital in Vietnam

Many hospitals in developing countries, including Vietnam, are facing the challenges of increasingly noncommunicable diseases and the financial autonomy policy from the government. To adapt to this new context requires understanding and changing the current organisational culture of the hospitals. However, little has been known about this in resource-constrained healthcare settings. The objectives of this study were to examine the four characteristics of the organisational culture and test selected individual and occupational differences in the organisational culture of a Vietnam central hospital. In a cross-sectional study using the Organisation Culture Assessment Instrument (OCAI) with the Competing Value Framework (CVF), including 4 factors, Clan, Adhocracy, Hierarchy, and Market, health workers currently working at Quang Nam General Hospital were interviewed. The results indicated the current cultural model was more internally focused with two dominant cultures, Clan and Hierarchy, while, for the desired model, the Clan culture was the most expected one. Comparing between the current and desired pattern, the down trend was found for all types of culture, except the Clan culture, and there were significant differences by domains of organisational culture. Furthermore, the current and desired models were differently distributed by key individual characteristics. These differences have raised a number of interesting directions for future research. They also suggest that, to build a hospital organisational culture to suit both current and future contexts as per employees' assessment and expectation, it is important to take individual and institutional variations into account.
Effect of Natural Compounds on NK Cell Activation

Natural killer (NK) cells are lymphocytes of the innate immune system that survey the body for stressed and abnormal cells. The integration of signals that they receive through various inhibitory and activating cell surface receptors controls their activation and ability to kill target cells and produce cytokines. In this manner, phenotypically and functionally distinct subsets of NK cells help protect against microbial infections and cancer and shape the adaptive immune response. NK cells can use two different mechanisms to kill their targets, either by cytotoxic granule exocytosis or by induction of death receptor-mediated apoptosis. Death ligands belong to the tumor necrosis factor (TNF) family of ligands. Upon release in close proximity to a cell slated for killing, perforin forms pores in the cell membrane of the target cell through which granzymes and associated molecules can enter and induce apoptosis. NK cells are also involved in antibody-dependent cellular toxicity via the CD16 receptor. In addition to target recognition, NK cells can be also activated by treatment with multiple compounds with stimulatory properties. Apart from interleukins, which belong to the best characterized group of NK cell-stimulating compounds, vitamins and constituents extracted from plants also display the ability to activate NK cells. The current review characterizes several groups of NK cell-activating compounds: vitamins belonging to classes A, B, C, D, and E, polysaccharides, lectins, and a number of phytochemicals used in cancer research, exhibiting stimulatory properties when applied to NK cells. Although in most cases the exact mechanism of action is not known, constituents described in this review seem to be promising candidates for NK cell-stimulating drugs.
The critical interplay between bone resorbing and bone forming cells.

AIM In this article, the interplay between bone resorbing and bone forming cells is reviewed. METHOD This review examines the comprehensive literature on the interaction between bone resorption and bone formation. RESULTS Coupling between bone resorption and bone formation refers to the process within basic multicellular units, in which osteoclastic bone resorption is met by the differentiation of osteoblasts and their bone forming activity. There are many possible signalling molecules that contribute to coupling at the asynchronously working remodelling sites throughout our skeleton. These include growth factors released from the bone matrix during bone resorption, soluble and membrane products of the osteoclasts and their precursors and signals from osteocytes. CONCLUSIONS In this review, we describe the potential roles of a number of these factors, whose interactions are essential for a tight control of coupling within individual remodelling units, in order to control skeletal mass. Both pre-clinical evidence and clinical evidence pinpoint that molecules in the WNT signalling pathway could be promising bone augmentation therapeutic targets. Regarding oral implications, there is support, from preclinical studies in rats, that anti-sclerostin antibodies can restore alveolar bone mass.
Long noncoding RNA PCAT6 inhibits colon cancer cell apoptosis by regulating anti-apoptotic protein ARC expression via EZH2

ABSTRACT Prostate cancer-associated ncRNA transcript 6 (PCAT6) is a long intergenic noncoding RNA that is involved in the progression of prostate and lung cancer, acting as a potential diagnostic and prognostic biomarker in nonsmall cell lung cancer. However, little is known about PCAT6 expression and its clinical significance in colon cancer. Here, we aimed to investigate the clinical significance of PCAT6 in colon cancer and its underlying mechanism. The expression of PCAT6 was analyzed in colon cancer tissues using public databases, and a series of in vitro and in vivo experiments was performed to investigate the biological functions of PCAT6 in colon cancer cells and the underlying mechanisms. Our results demonstrated that PCAT6 was upregulated in colon cancer tissues compared with that in noncancerous tissues, correlating with poorer clinical stages and a worse survival status. In vitro and in vivo experiments illustrated PCAT6 promoted cell growth and inhibited cell apoptosis in colon cancer. Mechanistically, PCAT6 enhanced the coenrichment of EZH2 and H3K4me3 at the apoptosis repressor with caspase recruitment domain (ARC) genomic region, promoting the transcriptional activity of ARC. Our data highlighted that PCAT6 acts as a key activator of ARC expression by forming a complex with EZH2, inhibiting cell apoptosis and contributing to colon cancer progression. These findings elucidated that PCAT6 may be a novel prognostic predictor and therapeutic target of colon cancer.
Krüppel like factor 6 splice variant 1 (KLF6-SV1) overexpression recruits macrophages to participate in lung cancer metastasis by up-regulating TWIST1

ABSTRACT The aim of this study was to investigate the mechanism by which KLF6-SV1 promoted lung cancer metastasis through tumor-associated macrophages (TAMs). Plasmid transfection was used to construct cells that upregulated or silenced gene. Tumor-bearing mouse model was established using A549 cells. SP staining was performed to detect the CD163 and CD68. Six-well plates and Transwell chamber were used for co-culture of lung cancer A549 cells and macrophages. CCK-8 and Transwell assay were applied to detected the cell viability and migration respectively. Protein and mRNA were tested by Western blot and quantitative real-time polymerase chain reaction (qRT-PCR). KLF6-SV1 overexpression promoted the expression levels of TWIST1 and CCL2, and also induce macrophage polarization to M2 and epithelial-mesenchymal transition (EMT). In vitro experiments showed that KLF6-SV1 might regulate the migration of lung cancer cells by regulating the expression of TWIST1 and CCL-2. M2 macrophages did not affect the expression of KLF6-SV1, TWIST1 and CCL-2. The co-culture system could up-regulate the EMT of A549 cells.Overexpression of KLF6-SV1 promoted the expression of TWIST1 and CCL2, and up-regulation of TWIST1 expression might promote the infiltration of M2 macrophages, which promoted the involvement of EMT in the metastasis of lung cancer cells.
Combined effects of DDE and hyperlipidic diet on metallothionein expression and synthesis in rat tissues

Metallothionein is well known for its detoxificant and anti‐oxidant properties and has been shown to be effective to prevent hydroxyl radical‐generated DNA degradation. The purpose of this investigation was to analyze the combined effect of two factors promoting cellular oxidative‐stress, that is, the administration of the pesticide dichloro–diphenyl–dichloroethylene (DDE) and a high fat diet, on metallothionein expression and synthesis in rat liver and kidney. DDE is the main metabolite of dichloro–diphenyl–trichloroethane (DDT), and is commonly found in the food chain and in all tissues of living organisms, carried by the fats. Male Wistar rats were fed with a standard (N) or a high fat (HF) diet and exposed to DDE (10 mg/kg body mass, N + DDE and HF + DDE groups) or vehicle (corn oil, N, and HF groups) via gavage every day for 28 days. Tissues histology was determined by light microscopy analysis; differences in metallothionein gene expression and synthesis by real‐time PCR and western blot, respectively. Finally, protein cellular localization was established by immunocytochemistry. The results showed a different involvement of metallothionein in defending tissues from HF‐ and DDE‐induced oxidative stress, suggesting that hepatic and renal cells use different strategies against pro‐oxidant species. In both cell types a marked increase in the metallothionein content was observed in the nucleus, with a concomitant drop of the cytoplasmatic protein, either under HF‐ and DDE‐stress conditions; however, no synergistic or additive effects were observed between the action of fats and pesticide. These findings reinforce the role of metallothionein in protecting DNA from oxidative damage.