Pirfenidone Reverts Global DNA Hypomethylation, Promoting DNMT1/UHRF/PCNA Coupling Complex in Experimental Hepatocarcinoma.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in the carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-Acetylaminofluorene (2-AAF). The HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, ß-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Influence of patient characteristics on microbial composition in surgical-site infections: insights from national surveillance study.

BACKGROUND: Although the impact of surgery- and patient-dependent factors on surgical-site infections (SSIs) have been studied extensively, their influence on the microbial composition of SSI remains unexplored. The aim of this study was to identify patient-dependent predictors of the microbial composition of SSIs across different types of surgery. METHODS: This retrospective cohort study included 538 893 patients from the Swiss national infection surveillance programme. Multilabel classification methods, adaptive boosting and Gaussian Naive Bayes were employed to identify predictors of the microbial composition of SSIs using 20 features, including sex, age, BMI, duration of surgery, type of surgery, and surgical antimicrobial prophylaxis. RESULTS: Overall, SSIs were recorded in 18 642 patients (3.8%) and, of these, 10 632 had microbiological wound swabs available. The most common pathogens identified in SSIs were Enterobacterales (57%), Staphylococcus spp. (31%), and Enterococcus spp. (28%). Age (mean feature importance 0.260, 95% c.i. 0.209 to 0.309), BMI (0.224, 0.177 to 0.271), and duration of surgery (0.221, 0.180 to 0.269) were strong and independent predictors of the microbial composition of SSIs. Increasing age and duration of surgical procedure as well as decreasing BMI were associated with a shift from Staphylococcus spp. to Enterobacterales and Enterococcus spp. An online application of the machine learning model is available for validation in other healthcare systems. CONCLUSION: Age, BMI, and duration of surgery were key predictors of the microbial composition of SSI, irrespective of the type of surgery, demonstrating the relevance of patient-dependent factors to the pathogenesis of SSIs.

Local infections are a frequent problem after surgery. The risk factors for surgical infections have been identified, but it is unclear which factors predict the type of microorganisms found in such infections. The aim of the present study was to assess patient factors affecting the composition of microorganisms in surgical infections. Data from 538 893 patients were analysed using standard statistics and machine learning methods. The results showed that age, BMI, and the duration of surgery were important in determining the bacteria found in the surgical-site infections. With increasing age, longer operations, and lower BMI, more bacteria stemming from the intestine were found in the surgical site, as opposed to bacteria from the skin. This knowledge may help in developing more personalized treatments for patients undergoing surgery in the future.

Multifunctional dietary interventions, low-grade inflammation and cardiometabolic profile: a scoping review.

Background: Growing evidence highlights the significant impact of diet to modify low-grade inflammation closely linked to cardiometabolic profile. Multifunctionnal diets, combining several compounds have been shown to beneficially impact metabolic parameters. Objective: This study synthesizes the knowledge on the impact of RCTs combining dietary multifunctional compounds on low-grade inflammation in humans. We investigate whether the effects of dietary multifunctional interventions on inflammatory markers were parallel to alterations of cardiometabolic parameters. Methodology: We considered both the integrated dietary interventions (ID, i.e. global diets such as Mediterranean, Nordic…) and the dietary interventions based on selected bioactive mix (BM) compounds, in healthy individuals and those at cardiometabolic risk. Out of 221 screened publications, we selected 27 studies: 11 for BM (polyphenols and/or omega-3 fatty acids and/or antioxidants and/or dietary fiber) and 16 for ID (Mediterranean, paleo, Nordic, Dietary Approaches to Stop Hypertension (DASH) diet…). Results: ID studies reflected significant improvements in inflammatory markers (CRP, IL-6, IL-10, IL-1b), concomitantly with beneficial changes in metabolic parameters. In BM studies, pronounced effects on low-grade inflammatory markers were observed, while improvements in metabolic parameters were not consistent. Both types of studies suggested a favorable impact on oxidative stress, a factor closely linked to the inflammatory profile. Conclusion: Our findings showed that multifunctional RCT diets have differential role in managing low-grade inflammation and cardiometabolic health, with a large heterogeneity in explored inflammatory markers. Further research is imperative to elucidate the link between low-grade inflammation and other cardiometabolic risk factors, such as intestinal inflammation or postprandial inflammatory dynamics, aiming to attain a comprehensive understanding of the mechanisms involved in these processes. These future investigations not only have the potential to deepen our insights into the connections among these elements but also pave the way for significant advancements in the prevention and management of conditions related to the cardiovascular and metabolic systems.

Functional identification of cis-regulatory long noncoding RNAs at controlled false discovery rates.

A key attribute of some long noncoding RNAs (lncRNAs) is their ability to regulate expression of neighbouring genes in cis. However, such 'cis-lncRNAs' are presently defined using ad hoc criteria that, we show, are prone to false-positive predictions. The resulting lack of cis-lncRNA catalogues hinders our understanding of their extent, characteristics and mechanisms. Here, we introduce TransCistor, a framework for defining and identifying cis-lncRNAs based on enrichment of targets amongst proximal genes. TransCistor's simple and conservative statistical models are compatible with functionally defined target gene maps generated by existing and future technologies. Using transcriptome-wide perturbation experiments for 268 human and 134 mouse lncRNAs, we provide the first large-scale survey of cis-lncRNAs. Known cis-lncRNAs are correctly identified, including XIST, LINC00240 and UMLILO, and predictions are consistent across analysis methods, perturbation types and independent experiments. We detect cis-activity in a minority of lncRNAs, primarily involving activators over repressors. Cis-lncRNAs are detected by both RNA interference and antisense oligonucleotide perturbations. Mechanistically, cis-lncRNA transcripts are observed to physically associate with their target genes and are weakly enriched with enhancer elements. In summary, TransCistor establishes a quantitative foundation for cis-lncRNAs, opening a path to elucidating their molecular mechanisms and biological significance.

The Omicron wave in Mexico: vaccine protection against progression to severe Covid-19 in SARS-CoV-2-infected workers.

OBJECTIVE: To assess the effectiveness of seven Covid-19 vaccines in preventing disease progression (DP) using data from national private sector workers during the Omicron wave in Mexico from January 2 to March 5, 2022. MATERIALS AND METHODS: This study employed an administrative retrospective cohort design, analyzing DP (hospitalization or death due to respiratory disease) among workers who filed a respiratory short-term disability claim and tested positive for SARS-CoV-2. Risk ratios (RRadj) were estimated using Poisson regression models adjusted for various factors. RESULTS: Vaccinated individuals had a lower risk of hospitalization and death compared with unvaccinated individuals. The overall RRadj for hospitalization and death were 0.36 (95%CI 0.32, 0.41) and 0.24 (0.17, 0.33), respectively. When evaluating vaccines individually, the RRadj for hospitalization were as follows Pfizer BioNTech 0.27 (95%CI 0.22, 0.33), Moderna 0.29 (95%CI 0.15, 0.57), Sinovac 0.32 (95%CI 0.25, 0.41), AstraZeneca 0.39 (95%CI 0.34, 0.46), Sputnik 0.39 (95%CI 0.28, 0.53), CanSino 0.41 (95%CI 0.24, 0.7), and Janssen 0.53 (95%CI 0.39, 0.72). The RRadj for death were as follows: Pfizer BioNTech 0.12 (95%CI 0.07, 0.19), Sputnik 0.15 (95%CI 0.06, 0.38), Sinovac 0.29 (95%CI 0.16, 0.53), AstraZeneca 0.30 (95%CI 0.20, 0.44), CanSino 0.38 (95%CI 0.1, 1.4), and Janssen 0.50 (95%CI 0.26, 0.97). CONCLUSION: Covid-19 vaccines significantly reduced the risk of severe disease during the Omicron wave in Mexico.

Neanderthal introgression in SCN9A impacts mechanical pain sensitivity.

The Nav1.7 voltage-gated sodium channel plays a key role in nociception. Three functional variants in the SCN9A gene (encoding M932L, V991L, and D1908G in Nav1.7), have recently been identified as stemming from Neanderthal introgression and to associate with pain symptomatology in UK BioBank data. In 1000 genomes data, these variants are absent in Europeans but common in Latin Americans. Analysing high-density genotype data from 7594 Latin Americans, we characterized Neanderthal introgression in SCN9A. We find that tracts of introgression occur on a Native American genomic background, have an average length of ~123 kb and overlap the M932L, V991L, and D1908G coding positions. Furthermore, we measured experimentally six pain thresholds in 1623 healthy Colombians. We found that Neanderthal ancestry in SCN9A is significantly associated with a lower mechanical pain threshold after sensitization with mustard oil and evidence of additivity of effects across Nav1.7 variants. Our findings support the reported association of Neanderthal Nav1.7 variants with clinical pain, define a specific sensory modality affected by archaic introgression in SCN9A and are consistent with independent effects of the Neanderthal variants on Nav1.7 function.

Complementary Nutritional Improvements of Cereal-Based Products to Reduce Postprandial Glycemic Response.

High glycemic response (GR) is part of cardiometabolic risk factors. Dietary polyphenols, starch digestibility, and dietary fibers could play a role in modulating GR. We formulated cereal products with high dietary fibers, polyphenols, and slowly digestible starch (SDS) contents to test their impact on the glycemic index (GI) and insulin index (II). Twelve healthy subjects were randomized in a crossover-controlled study to measure the GI and II of four biscuits according to ISO-26642(2010). Two types of biscuits were enriched with dietary fibers and polyphenols and high in SDS, and two similar control biscuits with low levels of these compounds were compared. The subjects consumed 50 g of available carbohydrates from the biscuits or from a glucose solution (reference). Glycemic and insulinemic responses were monitored for 2 h after the start of the consumption. The two enriched biscuits led to low GI and II (GI: 46 ± 5 SEM and 43 ± 4 SEM and II: 54 ± 5 SEM and 45 ± 3 SEM) when controls had moderate GI and II (GI: 57 ± 5 SEM and 58 ± 5 SEM and II: 61 ± 4 SEM and 61 ± 4 SEM). A significant difference of 11 and 15 units between the GI of enriched and control products was obtained. These differences may be explained by the polyphenol contents and high SDS levels in enriched products as well as potentially the dietary fiber content. This study provides new proposals of food formulations to induce beneficial health effects which need to be confirmed in a longer-term study in the context of the SINFONI consortium.

Association of PCSK1 and PPARG1 Allelic Variants with Obesity and Metabolic Syndrome in Mexican Adults.

Metabolic diseases, including obesity, diabetes, and metabolic syndrome, are among the most important public health challenges worldwide. Metabolic diseases are classified as multifactorial diseases in which genetic variants such as single-nucleotide polymorphisms (SNPs) may play an important role. The present study aimed to identify associations linking allelic variants of the PCSK1, TMEM18, GPX5, ZPR1, ZBTB16, and PPARG1 genes with anthropometric and biochemical traits and metabolic diseases (obesity or metabolic syndrome) in an adult population from northwestern Mexico. METHODS: Blood samples were collected from 523 subjects, including 247 with normal weight, 276 with obesity, and 147 with metabolic syndrome. Anthropometric and biochemical characteristics were recorded, and single-nucleotide polymorphisms (SNPs) were genotyped by real-time PCR. RESULTS: PCSK1 was significantly (p < 0.05) associated with BMI, weight, and waist-to-hip ratio; TMEM18 was significantly associated with systolic blood pressure and triglyceride levels; GPX5 was significantly associated with HDL cholesterol levels. In addition, PCSK1 was associated with obesity (p = 1.0 × 10-4) and metabolic syndrome (p = 3.0 × 10-3), whereas PPARG1 was associated with obesity (p = 0.044). CONCLUSIONS: The associations found in this study, mainly between allelic variants of PCSK1 and metabolic traits, obesity, and metabolic syndrome, may represent a risk for developing metabolic diseases in adult subjects from northwestern Mexico.

A dysregulated bile acids pool is associated with metabolic syndrome and gut microbial dysbiosis in early adolescence.

OBJECTIVE: The increased prevalence of childhood metabolic syndrome (MetS) is a public health issue. It has been shown that a dysregulated bile acid (BA) profile could be involved in the development of MetS, in which the gut microbiota could have a significant role in BA levels. This study aimed to evaluate differences in serum BA levels in children with and without MetS and whether these levels were associated with gut microbial composition. METHODS: A total of 100 children aged 10 to 12 years were enrolled in this study, 42 children with MetS (cases) and 58 control participants. Serum BAs were measured by liquid chromatography-tandem mass spectrometry and gut microbiota was determined by 16S ribosomal RNA gene sequencing. RESULTS: Children with MetS showed higher levels of total, secondary, and 12α-hydroxylated BAs, as well as deoxycholic acid, and these were associated with dyslipidemia and insulin resistance markers. Interestingly, total BAs were negatively correlated with gut bacterial diversity (Shannon index: rho = -0.218, p = 0.035), whereas total, 12α-hydroxylated, and secondary BAs, as well as deoxycholic acid, showed negative correlations with genera known for their potential health effects, including Bifidobacterium, Akkermansia, and Faecalibacterium. CONCLUSIONS: This study suggests that childhood MetS is associated with a dysregulated BA pool and that these alterations could influence the abundance of potentially beneficial bacteria, thus contributing to gut microbial dysbiosis.

Small area vulnerability, household food insecurity and child malnutrition in Medellin, Colombia: results from a repeated cross-sectional study.

Background: Malnutrition and food insecurity might be driven not only by individual factors but also by contextual conditions, such as area-level deprivation or vulnerability. This study aimed to analyze the association between area-level vulnerability and i) household food insecurity and ii) malnutrition in children in Medellin, Colombia, during the years 2017 and 2018. Methods: We obtained data from two different sources: the Living Standards Measurement Survey (LSMS) and the nutrition surveillance system of Medellin. The main outcomes were food insecurity in households with children and anthropometric indicators for children under five. The main predictor was area-level vulnerability. Mixed effects Poisson regression with robust standard errors models were conducted to test the association of quintiles of deprivation with each outcome. Findings: Households with children living in areas with the highest deprivation had 1.9 times the prevalence of food insecurity as compared to those living in areas with the lowest deprivation (PR 1.91, 95% CI 1.42-2.57). Similar results were observed for underweight/risk of underweight (PR 1.26, 95% CI 1.11-1.42), stunting/risk of stunting (PR 1.36, 95% CI 1.22-1.53) and stunting (PR 1.93 95% CI 1.55-2.39) among children under five. We found no consistent associations with wasting/risk of wasting or excess weight/risk of overweight across quintiles of deprivation. Interpretation: This study sheds light on the role of area-level vulnerability on malnutrition in children in Medellin, Colombia, showing a pattern of increasing prevalence of food insecurity, underweight and stunting by quintile of deprivation. Funding: Swiss School of Public Health (SSPH+) and Centre for Global Health Inequalities Research (CHAIN).

Analysis of Educational Attainment in a Mexican Psychiatric Patient Population with Bipolar or Psychotic Disorders.

Schizophrenia has been associated with premorbid poor educational performance and low educational attainment (EA). However, some studies have found positive associations between psychotic disorders and excellent scholastic performance. In the present study, we examined the association between EA and several clinical and nonclinical characteristics in psychiatric patients diagnosed with psychotic or bipolar disorders. Data were obtained from the files of 1132 patients who entered a major Mexico City psychiatric hospital during the years 2009-2010 for the treatment of psychotic symptoms and who were subsequently diagnosed with schizophrenia, bipolar, schizoaffective, or another psychotic disorder. Chi-squared tests, t-tests, and Cox regression analysis were applied to explore associations between EA and factors including gender, familial history of mental illness, premorbid personality characteristics, age of symptom onset, diagnosis, civil status, and current employment. Family history of mental illness decreased the hazard of having lower EA (B = -0.137, p = 0.025, ExpB = 0.872, 95% CI = 0.774-0.983), while a schizophrenia diagnosis independently increased it (B = 0.201, p = 0.004, ExpB = 1.223, 95% CI = 1.068-1.401). In male patients (but not in females), family history of mental illness was significantly associated with higher EA, while in female patients, premorbid schizoid-like personality characteristics were associated with lower EA. For both genders, lower EA was associated with having more children and being employed in manual labor, while higher EA was associated with professional employment. Conclusions: Compared with bipolar disorder, a schizophrenia diagnosis is associated with lower EA; however, familial history of mental illness and premorbid schizoid-like characteristics independently favor higher and lower EA in males and females, respectively. Since lower EA is generally associated with a lower economic status, special preventative attention should be given to students at high risk for schizophrenia, particularly those displaying a schizoid-like personality.

Description of the first global outbreak of mpox: an analysis of global surveillance data.

BACKGROUND: In May 2022, several countries with no history of sustained community transmission of mpox (formerly known as monkeypox) notified WHO of new mpox cases. These cases were soon followed by a large-scale outbreak, which unfolded across the world, driven by local, in-country transmission within previously unaffected countries. On July 23, 2022, WHO declared the outbreak a Public Health Emergency of International Concern. Here, we aim to describe the main epidemiological features of this outbreak, the largest reported to date. METHODS: In this analysis of global surveillance data we analysed data for all confirmed mpox cases reported by WHO Member States through the global surveillance system from Jan 1, 2022, to Jan 29, 2023. Data included daily aggregated numbers of mpox cases by country and a case reporting form (CRF) containing information on demographics, clinical presentation, epidemiological exposure factors, and laboratory testing. We used the data to (1) describe the key epidemiological and clinical features of cases; (2) analyse risk factors for hospitalisation (by multivariable mixed-effects binary logistic regression); and (3) retrospectively analyse transmission trends. Sequencing data from GISAID and GenBank were used to analyse monkeypox virus (MPXV) genetic diversity. FINDINGS: Data from 82 807 cases with submitted CRFs were included in the analysis. Cases were primarily due to clade IIb MPXV (mainly lineage B.1, followed by lineage A.2). The outbreak was driven by transmission among males (73 560 [96·4%] of 76 293 cases) who self-identify as men who have sex with men (25 938 [86·9%] of 29 854 cases). The most common reported route of transmission was sexual contact (14 941 [68·7%] of 21 749). 3927 (7·3%) of 54 117 cases were hospitalised, with increased odds for those aged younger than 5 years (adjusted odds ratio 2·12 [95% CI 1·32-3·40], p=0·0020), aged 65 years and older (1·54 [1·05-2·25], p=0·026), female cases (1·61 [1·35-1·91], p<0·0001), and for cases who are immunosuppressed either due to being HIV positive and immunosuppressed (2·00 [1·68-2·37], p<0·0001), or other immunocompromising conditions (3·47 [1·84-6·54], p=0·0001). INTERPRETATION: Continued global surveillance allowed WHO to monitor the epidemic, identify risk factors, and inform the public health response. The outbreak can be attributed to clade IIb MPXV spread by newly described modes of transmission. FUNDING: WHO Contingency Fund for Emergencies. TRANSLATIONS: For the French and Spanish translations of the abstract see Supplementary Materials section.

Tumour mutations in long noncoding RNAs enhance cell fitness.

Long noncoding RNAs (lncRNAs) are linked to cancer via pathogenic changes in their expression levels. Yet, it remains unclear whether lncRNAs can also impact tumour cell fitness via function-altering somatic "driver" mutations. To search for such driver-lncRNAs, we here perform a genome-wide analysis of fitness-altering single nucleotide variants (SNVs) across a cohort of 2583 primary and 3527 metastatic tumours. The resulting 54 mutated and positively-selected lncRNAs are significantly enriched for previously-reported cancer genes and a range of clinical and genomic features. A number of these lncRNAs promote tumour cell proliferation when overexpressed in in vitro models. Our results also highlight a dense SNV hotspot in the widely-studied NEAT1 oncogene. To directly evaluate the functional significance of NEAT1 SNVs, we use in cellulo mutagenesis to introduce tumour-like mutations in the gene and observe a significant and reproducible increase in cell fitness, both in vitro and in a mouse model. Mechanistic studies reveal that SNVs remodel the NEAT1 ribonucleoprotein and boost subnuclear paraspeckles. In summary, this work demonstrates the utility of driver analysis for mapping cancer-promoting lncRNAs, and provides experimental evidence that somatic mutations can act through lncRNAs to enhance pathological cancer cell fitness.

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape.

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10-8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features.

Pirfenidone Protects from UVB-Induced Photodamage in Hairless Mice.

BACKGROUND: Ultraviolet radiation (UV) is the main environmental factor that causes histological degenerative changes of the skin giving rise to a chronic process called photodamage. Non-melanoma skin cancer induced by UVB radiation is a result of a cascade of molecular events caused by DNA damage in epidermis cells, including persistent inflammation, oxidative stress, and suppression of T cell-mediated immunity. Retinoids such as tretinoin have been widely used in skin to treat photoaging and photodamage, though its secondary adverse effects have been recognized. Pirfenidone (PFD) has emerged as an antifibrogenic, anti-inflammatory and antioxidant agent, and in this work its efficacy was evaluated in a model of UVB-induced photodamage. METHODS: Epidermal, dermal, and inflammatory changes were measured by histomorphometric parameters. In addition, gene, and protein expression of key molecules in these processes were evaluated. RESULTS: Our results revealed an anti-photodamage effect of topical PFD with absence of inflammatory skin lesions determined by dermoscopy. In addition, PFD reduced elastosis, improved organization, arrangement, and deposition of dermal collagens, downregulated several pro-inflammatory markers such as NF-kB, IL-1, IL-6 and TNFα, and decreased keratinocyte damage. CONCLUSION: Topical pirfenidone represents a promising agent for the treatment of cell photodamage in humans. Clinical trials need to be carried out to explore this premise.

A metagenomic study identifies a Prevotella copri enriched microbial profile associated with non-alcoholic steatohepatitis in subjects with obesity.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease. Increasing evidence indicates that the gut microbiota can play an important role in the pathophysiology of NAFLD. Recently, several studies have tested the predictive value of gut microbiome profiles in NAFLD progression; however, comparisons of microbial signatures in NAFLD or non-alcoholic steatohepatitis (NASH) have produced discrepant results, possibly due to ethnic and environmental factors. Thus, we aimed to characterize the gut metagenome composition of patients with fatty liver disease. METHODS: Gut microbiome of 45 well-characterized patients with obesity and biopsy-proven NAFLD was evaluated using shot-gun sequencing: 11 non-alcoholic fatty liver controls (non-NAFL), 11 with fatty liver, and 23 with NASH. RESULTS: Our study showed that Parabacteroides distasonis and Alistipes putredenis were enriched in fatty liver but not in NASH patients. Notably, in a hierarchical clustering analysis, microbial profiles were differentially distributed among groups, and membership to a Prevotella copri dominant cluster was associated with a greater risk of developing NASH. Functional analyses showed that although no differences in LPS biosynthesis pathways were observed, Prevotella-dominant subjects had higher circulating levels of LPS and a lower abundance of pathways encoding butyrate production. CONCLUSIONS: Our findings suggest that a Prevotella copri dominant bacterial community is associated with a greater risk for NAFLD disease progression, probably linked to higher intestinal permeability and lower capacity for butyrate production.

Antifungal Activity of Selenium Nanoparticles Obtained by Plant-Mediated Synthesis.

The continuous need to satisfy world food demand has led to the search for new alternatives to combat economic losses in agriculture caused by phytopathogenic fungi. These organisms cause plant diseases, reducing their productivity and decreasing fruit quality. Among the new tools being explored is nanotechnology. Nanoparticles with antimicrobial properties could be an excellent alternative to address this problem. In this work, selenium nanoparticles (SeNPs) were obtained using plant extracts of Amphipterygium glaucum leaves (SeNPs-AGL) and Calendula officinalis flowers (SeNPs-COF). Characterization of the SeNPs was performed and their ability as antifungal agents against two commercially relevant plant pathogenic fungi, Fusarium oxysporum and Colletotrichum gloeosporioides, was evaluated. Assays were performed with different concentrations of SeNPs (0, 0.25, 0.5, 1.0, and 1.7 mg/mL). It was observed that both SeNPs had antifungal activity against both plant pathogens at concentrations of 0.25 mg/mL and above. SeNPs-AGL demonstrated better antifungal activity and smaller size (around 8.0 nm) than SeNPs-COF (134.0 nm). FTIR analysis evidenced the existence of different functional groups that constitute both types of SeNPs. There are factors that have to be considered in the antimicrobial activity of SeNPs such as nanoparticle size and phytochemical composition of the plant extracts used, as these may affect their bioavailability.

Oxidative and Fibrinolytic Mechanisms: Two Important Processes to Consider in Platelet Storage

Objective: Platelet-rich plasma (PRP) is used in multiple coagulation disorders. Its therapeutic effectiveness relies on technical procedures related to PRP procurement and preservation because free radicals induce platelet activation and aging. This work aims to elucidate the oxidative mechanisms involved in activation of platelets obtained from PRP during storage. Materials and Methods: One hundred ten PRP batches were obtained from healthy donors and kept under stirring at a temperature of 20-24 °C. Protein extraction was performed from platelet homogenates and plasma at different times of storage from day 1 to 20. The activities of antioxidant markers such as catalase (CAT), superoxide dismutase, and ceruloplasmin, as well as fibrinolytic protein activity metalloproteases 2 and 3, plasmin, and urokinase plasminogen activator, were analyzed by zymography assays. Oxidized proteins were also determined. Results: Significant activity of antioxidant enzymes and fibrinolytic molecules was observed on day 5 of storage in PRP homogenates, which increased over time and was concomitantly correlated with oxidized protein levels. Reverse enzymatic activity patterns were observed in plasma, except for CAT, which remained unchanged. Conclusion: Storage conditions of platelets from PRP for up to 5 days induced in vitro platelet activation by oxidative damage and proteolysis. This finding confirms the need for proper management of these blood products to preserve their viability and functionality.

Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions.

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5-9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: -4.0 kg (-2.9%) in patient 1, and -1.8 kg (-1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (-2.9 kg; -2.8%). Phentermine treatment produced similar weight loss in six carriers (-12.7 kg; 15.5%) and 18 non-carriers (-11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.