Single-point and kinetics of peripheral residual disease by mass spectrometry to predict outcome in patients with high risk smoldering multiple myeloma included in the GEM-CESAR trial.

The value of quantitative immunoprecipitation mass spectrometry (QIP-MS) to identify the M-protein is being investigated in patients with monoclonal gammopathies but no data are yet available in high-risk smoldering myeloma (HRsMM). We have therefore investigated QIP-MS to monitor peripheral residual disease (PRD) in 62 HRsMM patients enrolled in the GEM-CESAR trial. After 24 cycles of maintenance, detecting the M-protein by MS or clonal plasma cells by NGF identified cases with a significantly shorter median PFS (mPFS; MS: not reached vs 1,4 years, p=0.001; NGF: not reached vs 2 years, p=0.0002) but reaching CR+sCR did not discriminate patients with different outcome. With NGF as a reference, the combined results of NGF and MS showed a high negative predictive value (NPV) of MS: 81% overall and 73% at treatment completion. When sequential results were considered, sustained negativity by MS or NGF was associated with a very favorable outcome with a mPFS not yet reached vs 1.66 years and 2.18 years in cases never attaining PRD or minimal residual disease (MRD) negativity, respectively. We can thus conclude that 1) the standard response categories of the IMWG do not seem to be useful for treatment monitoring in HRsMM patients, 2) MS could be used as a non-invasive, clinical valuable tool with the capacity of guiding timely bone marrow evaluations (based on its high NPV with NGF as a reference) and 3) similarly to NGF, sequential results of MS are able identify a subgroup of HRsMM patients with long-term disease control. This study was registered at www.clinicaltrials.gov (ClinicalTrials.gov identifier: NCT02415413).

The Use of Event Related Potentials to Predict Amyloid PET Status Among Patients from a Memory Disorders Clinic.

Background: Amyloid positron emission tomography (PET) scans provide in vivo evidence of Alzheimer's disease (AD); however, their high cost limits their use in standard clinical care. Event related potentials (ERPs) may represent an inexpensive and non-invasive additional method for detecting AD pathology. Objective: We investigated whether ERPs, along with neuropsychological data, serve as predictors of amyloid PET status in patients with memory complaints. Methods: Veterans aged 50-100 were recruited from a memory disorders clinic. Participants underwent a neuropsychological battery and an ERP auditory oddball protocol. Twenty-eight patients had a positive amyloid PET scan, and thirty-nine patients had a negative scan. Results: ERP-P200 target amplitude and P200 standard latency were predictors of amyloid PET status. When submitting to ROC analysis, P200 standard latency exhibited the highest specificity and sensitivity in predicting amyloid PET positivity, correctly classifying the amyloid PET status for 86% of patients. Conclusions: ERP-P200 measures are strong indicators of amyloid-ß presence in patients from a memory disorder clinic. Increased P200 amplitude and decreased P200 latency in patients with a positive amyloid PET scan may be attributed to hyperactivation of perceptual bottom-up processes compensating for AD-related synaptic loss in the fronto-parietal networks.

Promoting workplace retention during global crises: An international survey of the preventive role of psychological support among victims of social discrimination in long-term care facilities.

This international cross-sectional survey examined the potential role of organizational psychological support in mitigating the association between experiencing social discrimination against long-term care (LTC) facilities' healthcare professionals (HCPs) and their intention to stay in the current workplace during the COVID-19 pandemic. Participants included a convenience sample of 2,143 HCPs (nurses [21.5 %], nurse aids or residential care workers [40.1 %], social workers [12.1 %], and others [26.4 %]) working at 223 LTC facilities in 13 countries/regions. About 37.5 % of the participants reported experiencing social discrimination, and the percentage ranged from 15.3 % to 77.9 % across countries/regions. Controlling for socio-demographic and work-related variables, experiencing social discrimination was significantly associated with a lower intention to stay, whereas receiving psychological support showed a statistically significant positive association (p-value=0.015 and <0.001, respectively). The interaction term between social discrimination and psychological support showed a statistically significant positive association with the intention to stay, indicating a moderating role of the psychological support.

Smart polymers and smartphones for Betalain measurement in cooked beetroots.

Betalains in beetroots offer notable colouring properties and health benefits, including antioxidant, anti-inflammatory, hepatoprotective, and antitumorous activities. However, they degrade due to processing and storage conditions like temperature, pH, oxygen, and light-exposure. Traditional betalain determination methods are resource-intensive solid-liquid extractions. This study proposes a novel approach using a smart polymer to rapidly quantify betalains in processed beetroots. The polymer, containing N,N-dimethylaminoethyl methacrylate, selectively interacts with compounds like betalains. Characterization shows thermal stability over 250 °C and suitable mechanical properties. The film changes to colour upon interaction with betalains, allowing quantification via smartphone. The sensory polymer's efficacy was validated across 27 beetroot samples, showing no significant differences compared to traditional methods. Combining the smart polymer with a colour analysis app, "Colorimetric Titration," provides a robust and efficient means of quantifying total betalains in beetroot puree, reducing the quantification time from 180 to 90 min, promising implications for routine food industry quality assessments.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). METHODS AND RESULTS: This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3 months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5 L (interquartile range 0-1.6 L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21 mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P = 0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P < 0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P < 0.001) with an optimal cut-off of 1.2 L. CONCLUSIONS: VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3 months.

Curative Strategy for High-Risk Smoldering Myeloma: Carfilzomib, Lenalidomide, and Dexamethasone (KRd) Followed by Transplant, KRd Consolidation, and Rd Maintenance.

PURPOSE: Early treatment of high-risk smoldering myeloma has been shown to delay progression to multiple myeloma (MM). We conducted this trial with curative intention using a treatment approach employed for newly diagnosed patients with MM. METHODS: Patients with high-risk smoldering myeloma (>50% progression risk at 2 years) and transplant candidates were included and received induction therapy with carfilzomib, lenalidomide, and dexamethasone (KRd), six cycles, followed by high-dose melphalan (200 mg/m2) autologous stem-cell transplantation (HDM-ASCT), two KRd consolidation cycles, and Rd maintenance for 2 years. The primary end point was undetectable measurable residual disease (uMRD) rate by next-generation flow after ASCT. Sustained uMRD 4 years after ASCT was the secondary end point. RESULTS: Between June 2015 and June 2017, 90 patients were included, and 31% met at least one SixtyLightchain MRI (SLiM)-hypercalcemia, renal impairment, anemia, bone disease (CRAB) criterion. After a median follow-up of 70.1 months, 3 months after ASCT, in the intention-to-treat population, 56 (62%) of 90 patients had uMRD, and 4 years later, it was sustained in 29 patients (31%). Five patients progressed to MM, and the 70-month progression rate was 94% (95% CI, 84 to 89). The presence of any SLiM CRAB criteria predicted progression to MM (four of the five patients; hazard ratio, 0.12; 95% CI, 0.14 to 1.13; P = .03). Thirty-six patients showed biochemical progression, and failure to achieve uMRD at the end of treatment predicted it. The 70-month overall survival was 92% (95% CI, 82 to 89). Neutropenia and infections were the most frequent adverse events during treatment, resulting in one treatment-related death. Three second primary malignancies have been reported. CONCLUSION: Although a longer follow-up is needed, this curative approach is encouraging and more effective than active MM, with 31% of the patients maintaining the uMRD 4 years after HDM-ASCT.

Microplastic pollution and nutrient enrichment shift the diet of freshwater macroinvertebrates.

Microplastic pollution poses a global threat to freshwater ecosystems, with laboratory experiments indicating potential toxic impacts through chemical toxicity, physical abrasion, and false satiation. Bioplastics have emerged as a potential greener alternative to traditional oil-based plastics. Yet, their environmental effects remain unclear, particularly at scales relevant to the natural environment. Additionally, the interactive impacts of microplastics with other environmental stressors, such as nutrient enrichment, are poorly understood and rarely studied. Under natural conditions organisms might be able to mitigate the toxic effects of microplastics by shifting their diet, but this ability may be compromised by other stressors. This study combines an outdoor mesocosm experiment and stable isotope analysis to determine changes in the trophic niches of three freshwater invertebrate species exposed to conventional (HDPE) and bio-based biodegradable (PLA) microplastics at two concentrations, both independently and combined with nutrient enrichment. Exposure to microplastics altered the isotopic niches of two of the invertebrate species, with nutrient enrichment mediating this effect. Moreover, the effects of microplastics were consistent regardless of their type or concentration. Under enriched conditions, two of the species exposed to microplastics shifted to a specialised diet compared with controls, whereas little difference was observed between the isotopic niches of those exposed to microplastic and controls under ambient nutrient conditions. Additionally, PLA was estimated to support 24 % of the diet of one species, highlighting the potential assimilation of bioplastics by biota and possible implications. Overall, these findings suggest that the toxic effects of microplastics suggested from laboratory studies might not manifest under real-world conditions. However, this study does demonstrate that subtle sublethal effects occur even at environmentally realistic microplastic concentrations. The crucial role of nutrient enrichment in mediating microplastic effects underscores the importance of considering microplastic pollution in the context of other environmental stressors.

Effects of massive desiccation of olive waste residues on air quality.

New industries are proliferating in the recovery of agri-food wastes, such as those involved in the revaluation of alperujo, generated in the production of olive oil. Despite the potential environmental benefits, their activity is not exempt from new forms of emissions, aggravated by the massification of waste treatments. This work reports a six-month field campaign carried out in an alperujo desiccation plant which can serve as a proxy for these emerging industries in the Mediterranean countries. The study focused on air quality parameters, covering criteria pollutants, metals and microbiological load of particulate matter and the characterization of volatile organic compounds (VOCs). The results show a slight contribution of the factory to the NOx levels in the surroundings (3.0-12.5 µg/m3). Statistically significant effects were not observed for ozone, CO, SO2, or PM10. Concerning the levels of metals, concentrations were low and calculated health risk indexes indicated safe conditions in the area. The most abundant elements were Na (6.5 × 102 ng/m3), K (4.0 × 102 ng/m3), Al (2.7 × 102 ng/m3), Zn (2.1 × 102 ng/m3), Ca (2.16 × 102 ng/m3), Fe (3.6 × 101 ng/m3) and Mg (3.2 × 101 ng/m3). Bacterial counts, with a mean value of 15.9 CFU/m3, showed a seasonal shift, mainly explained by weather (air moisture and temperature) and PM2.5 concentration. The genomic analysis showed Cutibacterium as the dominant genus during the cold months while Bacillus predominated in the warm season. The VOCs with higher average concentrations were acetic acid (130 µg/m3), nonanoic acid (124 µg/m3), benzoic acid (29.7 µg/m3), octanoic acid (19.9 µg/m3) and nonanal (4.70 µg/m3), with the rest of compounds in concentrations below 4 µg/m3. Odorant pollutants with the greatest contribution to olfactory nuisance were aldehydes (from pentanaldehyde to decanaldehyde), acetic acid and phenol. Although the observable effects of the waste treatments were low, several parameters showed an influence on the environment which should be assessed to foresee and prevent long-term consequences.

Zinc-Catalyzed Cyclization of Alkynyl Derivatives: Substrate Scope and Mechanistic Insights.

Novel alkyl zinc complexes supported by acetamidate/thioacetamidate heteroscorpionate ligands have been successfully synthesized and characterized. These complexes exhibited different coordination modes depending on the electronic and steric effects of the acetamidate/thioacetamidate moiety. Their catalytic activity has been tested toward the hydroelementation reactions of alkynyl alcohol/acid substrates, affording the corresponding enol ether/unsaturated lactone products under mild reaction conditions. Kinetic studies have been performed and confirmed that reactions are first-order in [catalyst] and zero-order in [alkynyl substrate]. DFT calculations supported a reaction mechanism through the formation of the catalytically active species, an alkoxide-zinc intermediate, by a protonolysis reaction of the Zn-alkyl bond with the alcohol group of the substrate. Based on the experimental and theoretical results, a catalytic cycle has been proposed.

Eating disorder symptoms and weight pressure in female rowers: associations between self-concept, psychological well-being and body composition.

BACKGROUND: Female rowers may be at risk of eating disorders and high weight pressure. AIM: The purpose of the study was to investigate the prevalence of disordered eating symptoms and weight-related pressure and the associations with self-concept, psychological well-being, socio-demographic data, experience, performance level and body composition in female fixed-bench rowers. METHODS: Female rowers (n = 208; age ranged mean ± SD 23.6 ± 6.5 years) completed the SCOFF scale, Weight-Pressures in Sport-Females (WPS-F), Physical Self-Concept Questionnaire and the Ryff scales of psychological well-being and provided information on their experience and level of competition. In a subgroup of 115 athletes, body composition was assessed using bioimpedance. RESULTS: It was found that 42.3% of the athletes scored ≥ 2 on SCOFF and mean ± SD value of WPS-F score was 3.65 ± 0.82. Stepwise regression analysis revealed that self-concept of strength and pressure from teammates and the uniform were associated with higher ED symptoms, whereas better psychological well-being in terms of autonomy, self-concept of attractiveness, and age were protective factors for ED symptoms. BMI, athletes' physical condition, strength, and experience were associated with more weight-related pressure and better self-concept of attractiveness and physical well-being of autonomy were significantly associated with less pressure. In body composition analysis, higher extra cellular water, self-acceptance, and physical condition were associated with more weight-related pressure in female rowers, being attractiveness and the environmental mastery protective elements. CONCLUSIONS: The prevalence of ED symptomatology and weight-related pressure are high in female fixed bench rowing. The psychological factors of well-being and self-concept, team environment, body image concerns and body composition analysis should be considered to promote healthy eating behaviours in female rowers.

Athletes may be at increased risk of developing disordered eating behaviours that, if persistent, may lead to a diagnosis of an eating disorder. This can affect their health in the short and long term. The risk factors are many, and perceived weight-related pressures and psychological attitudes towards body image, appearance and concerns are less well understood. Female rowers are at high risk for eating disorder symptoms, and athletes' self-concept of strength and pressure from teammates and the uniform were associated as negative factors for eating disorder symptoms. On the other hand, better psychological well-being in terms of autonomy, self-concept of attractiveness and age were protective factors for eating disorder symptoms. Weight pressure was associated with higher body mass index, water retention, physical condition, strength and experience, whereas better self-concept of attractiveness and physical well-being were significantly associated with less pressure. Weight pressure and psychological attitudes towards body image have the role of protective/facilitating factors against the development of eating disorders. They should be taken into account when designing prevention and intervention programmes for athletes, coaches, parents and technical staff.

A Systematic Review of the Relationship between Social Isolation and Physical Health in Adults.

Background: According to the World Health Organization, social isolation, particularly of older adults, is a public health issue endangering the well-being of individuals, families, and communities. Social isolation affects health through biological, behavioral, and psychological pathways and is associated with physical and psychological/emotional well-being, increases morbidity and mortality rates, and lowers quality of life. Purpose: This systematic review examined the relationship between social isolation and physical health, including subjective and objective dimensions, and factors that influence this relationship in adults. Methods: This systematic review examined six electronic databases covering the field of health and human services and included results from 1 January 2017 to 10 March 2023 with key terms including adult social connection or social isolation coupled with health, physical, psychological, emotional, mental, or behavioral. The initial search yielded 925 research articles across all databases and was narrowed to 710 when the decision was made to focus on social isolation and physical health. Covidence was used throughout the retrieval and appraisal process, as provided in a PRISMA flow diagram. Twenty-four studies that scored 90 or above in the appraisal process were included in the systematic review. Results: The studies represented included seven studies conducted in the United States and seventeen studies conducted internationally. Regarding study design, twenty-three studies were quantitative, one was qualitative, and one was mixed methods. The majority of quantitative studies were correlational in design with nine being longitudinal. The majority of studies were based on large national data sets representing in total 298,653 participants aged 50 and older. The results indicate that social isolation is related to increases in inflammatory biomarkers associated with diseases, all-cause mortality, lower expectations of longevity, and frailty. In addition, social isolation was associated with cognitive decline and disruptions in sleep. Poor oral health increased social isolation. The results further indicated that decreased physical performance/function and a decline in physical activity were associated with social isolation, as well as decreased overall physical health, poor health behaviors, and self-care, and decreased health-related quality of life. Further research is warranted to examine the possible bidirectionality of these relationships and possible mediating, moderating, or confounding variables. Implications: Future research is needed to explore the biological and behavioral pathways in which social isolation negatively impacts physical health. Going forward, studies are needed that move beyond descriptive, exploratory methods and integrate data from qualitative and mixed-method designs that will inform the development and testing of a conceptual framework related to social isolation and health. By advancing the science behind social isolation, comprehensive interventions can be identified and tested with implications at the individual, family, community, and societal levels to reduce social isolation, particularly among adults, and improve health and quality of life.

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.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

A Novel Foodstuff Mixture Improves the Gut-Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients.

Microbial community control is crucial for maintaining homeostasis of the gut-liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)-Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)-enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice's liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars.

Striatal GDNF Neurons Chemoattract RET-Positive Dopamine Axons at Seven Times Farther Distance Than Medium Spiny Neurons.

Glial cell line-derived neurotrophic factor (GDNF) is among the strongest dopamine neuron function- and survival-promoting factors known. Due to this reason, it has clinical relevance in dopamine disorders such as Parkinson's disease and schizophrenia. In the striatum, GDNF is exclusively expressed in interneurons, which make up only about 0.6% of striatal cells. Despite clinical significance, histological analysis of striatal GDNF system arborization and relevance to incoming dopamine axons, which bear its receptor RET, has remained enigmatic. This is mainly due to the lack of antibodies able to visualize GDNF- and RET-positive cellular processes; here, we overcome this problem by using knock-in marker alleles. We find that GDNF neurons chemoattract RET+ axons at least seven times farther in distance than medium spiny neurons (MSNs), which make up 95% of striatal neurons. Furthermore, we provide evidence that tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, is enriched towards GDNF neurons in the dopamine axons. Finally, we find that GDNF neuron arborizations occupy approximately only twelve times less striatal volume than 135 times more abundant MSNs. Collectively, our results improve our understanding of how endogenous GDNF affects striatal dopamine system function.

Sulforaphane-mediated immune regulation through inhibition of NF-kB and MAPK signaling pathways in human dendritic cells.

Inflammation and immune responses are intricately intertwined processes crucial for maintaining homeostasis and combating against pathogens. These processes involve complex signaling pathways, notably the Nuclear Factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) pathways, which play crucial roles. Sulforaphane (SFN), a nutraceutic, has emerged as a potential regulator of NF-κB and MAPK signaling pathways, exhibiting anti-inflammatory properties. However, limited knowledge exists regarding SFN's effects on immune cell modulation. This study aimed to assess the immunomodulatory capacity of SFN pretreatment in human dendritic cells (DCs), followed by exposure to a chronic inflammatory environment induced by lipopolysaccharide. SFN pretreatment was found to inhibit the NF-κB and MAPK signaling pathways, resulting in phenotypic changes in DCs characterized by a slight reduction in the expression of surface markers, as well as a decrease of TNF-α/IL-10 ratio. Additionally, SFN pretreatment enhanced the proliferation of Treg-cells and promoted the production of IL-10 by B-cells before exposure to the chronic inflammatory environment. Furthermore, these changes in DCs were found to be influenced by the inhibition of NF-κB and MAPK pathways (specifically p38 MAPK and JNK), suggesting that these pathways may play a role in the regulation of the differentiation of adaptive immune responses (proliferation of T- and IL-10-producing regulatory-cells), prior to SFN pretreatment. Our findings suggest that SFN pretreatment may induce a regulatory response by inhibiting NF-κB and MAPK signaling pathways in an inflammatory environment. SFN could be considered a promising strategy for utilizing functional foods to protect against inflammation and develop immunoregulatory interventions.

Integrated miRNA-mRNA Analysis Reveals Critical miRNAs and Targets in Diet-Induced Obesity-Related Glomerulopathy.

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Parenting practices as a buffer in the relationship between exposure to community violence and bullying in Mexican adolescents.

Multiple studies have shown that adolescents exposed to community violence are likely to engage in bullying behaviors. However, we still need to understand which variables can help reduce the influence of community violence exposure (CVE) on bullying. To investigate this question, a study was conducted with a sample of 568 Mexican adolescents, comprising 276 (48.6%) males and 292 (51.4%) females aged 12 to 16 years old (M age = 13.7 years, SD = 0.82). The study examined how parental support (PS) and parental induction to justice sensitivity (JS) can moderate the relationship between CVE and bullying. The study used structural equation modeling with latent variables. The results showed that CVE was positively associated with bullying, whereas PS and the induction to perpetrator JS were negatively associated. The moderation analysis suggests that the relationship between CVE and bullying was weaker among adolescents who received high PS. On the other hand, low and high parental induction to JS had the same moderating effect. Based on the findings, parental practices are critical when developing preventive programs to reduce the harmful effects of CVE on bullying behavior.