Harnessing Immunomodulatory Polymers for Treatment of Autoimmunity, Allergy, and Transplant Rejection.

Autoimmunity, allergy, and transplant rejection are a collection of chronic diseases that are currently incurable, drastically decrease patient quality of life, and consume considerable health care resources. Underlying each of these diseases is a dysregulated immune system that results in the mounting of an inflammatory response against self or an innocuous antigen. As a consequence, afflicted patients are required to adhere to lifelong regimens of multiple immunomodulatory drugs to control disease and reclaim agency. Unfortunately, current immunomodulatory drugs are associated with a myriad of side effects and adverse events, such as increased risk of cancer and increased risk of serious infection, which negatively impacts patient adherence rates and quality of life. The field of immunoengineering is a new discipline that aims to harness endogenous biological pathways to thwart disease and minimize side effects using novel biomaterial-based strategies. We highlight and discuss polymeric micro/nanoparticles with inherent immunomodulatory properties that are currently under investigation in biomaterial-based therapies for treatment of autoimmunity, allergy, and transplant rejection.

APLpred: A machine learning-based tool for accurate prediction and characterization of asparagine peptide lyases using sequence-derived optimal features.

Asparagine peptide lyase (APL) is among the seven groups of proteases, also known as proteolytic enzymes, which are classified according to their catalytic residue. APLs are synthesized as precursors or propeptides that undergo self-cleavage through autoproteolytic reaction. At present, APLs are grouped into 10 families belonging to six different clans of proteases. Recognizing their critical roles in many biological processes including virus maturation, and virulence, accurate identification and characterization of APLs is indispensable. Experimental identification and characterization of APLs is laborious and time-consuming. Here, we developed APLpred, a novel support vector machine (SVM) based predictor that can predict APLs from the primary sequences. APLpred was developed using Boruta-based optimal features derived from seven encodings and subsequently trained using five machine learning algorithms. After evaluating each model on an independent dataset, we selected APLpred (an SVM-based model) due to its consistent performance during cross-validation and independent evaluation. We anticipate APLpred will be an effective tool for identifying APLs. This could aid in designing inhibitors against these enzymes and exploring their functions. The APLpred web server is freely available at https://procarb.org/APLpred/.

Computational prediction of phosphorylation sites of SARS-CoV-2 infection using feature fusion and optimization strategies.

SARS-CoV-2's global spread has instigated a critical health and economic emergency, impacting countless individuals. Understanding the virus's phosphorylation sites is vital to unravel the molecular intricacies of the infection and subsequent changes in host cellular processes. Several computational methods have been proposed to identify phosphorylation sites, typically focusing on specific residue (S/T) or Y phosphorylation sites. Unfortunately, current predictive tools perform best on these specific residues and may not extend their efficacy to other residues, emphasizing the urgent need for enhanced methodologies. In this study, we developed a novel predictor that integrated all the residues (STY) phosphorylation sites information. We extracted ten different feature descriptors, primarily derived from composition, evolutionary, and position-specific information, and assessed their discriminative power through five classifiers. Our results indicated that Light Gradient Boosting (LGB) showed superior performance, and five descriptors displayed excellent discriminative capabilities. Subsequently, we identified the top two integrated features have high discriminative capability and trained with LGB to develop the final prediction model, LGB-IPs. The proposed approach shows an excellent performance on 10-fold cross-validation with an ACC, MCC, and AUC values of 0.831, 0.662, 0.907, respectively. Notably, these performances are replicated in the independent evaluation. Consequently, our approach may provide valuable insights into the phosphorylation mechanisms in SARS-CoV-2 infection for biomedical researchers.

Lack of leisure time physical activity and variations in cardiovascular mortality across US communities: a comprehensive county-level analysis (2011-2019).

OBJECTIVES: To investigate the associations between county-level proportions of adults not engaging in leisure-time physical activity (no LTPA) and age-adjusted cardiovascular mortality (AACVM) rates in the overall US population and across demographics. METHODS: Analysing 2900 US counties from 2011 to 2019, we used the Centers for Disease Control and Prevention (CDC) databases to obtain annual AACVM rates. No LTPA data were sourced from the CDC's Behavioural Risk Factor Surveillance System survey and county-specific rates were calculated using a validated multilevel regression and poststratification modelling approach. Multiple regression models assessed associations with county characteristics such as socioeconomic, environmental, clinical and healthcare access factors. Poisson generalised linear mixed models were employed to calculate incidence rate ratios (IRR) and additional yearly deaths (AYD) per 100 000 persons. RESULTS: Of 309.9 million residents in 2900 counties in 2011, 7.38 million (2.4%) cardiovascular deaths occurred by 2019. County attributes such as socioeconomic, environmental and clinical factors accounted for up to 65% (adjusted R2=0.65) of variance in no LTPA rates. No LTPA rates associated with higher AACVM across demographics, notably among middle-aged adults (standardised IRR: 1.06; 95% CI (1.04 to 1.07)), particularly women (1.09; 95% CI (1.07 to 1.12)). The highest AYDs were among elderly non-Hispanic black individuals (AYD=68/100 000). CONCLUSIONS: Our study reveals a robust association between the high prevalence of no LTPA and elevated AACVM rates beyond other social determinants. The most at-risk groups were middle-aged women and elderly non-Hispanic black individuals. Further, county-level characteristics accounted for substantial variance in community LTPA rates. These results emphasise the need for targeted public health measures to boost physical activity, especially in high-risk communities, to reduce AACVM.

Closing the Gaps in Care of Dyslipidemia: Revolutionizing Management with Digital Health and Innovative Care Models.

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. These concepts on the level of healthcare policy not only inform reimbursements but also define the standard of care. Next, we consider the advances in atherosclerotic cardiovascular disease risk score calculators as well as evolving imaging modalities. The impact and growth of digital health, ranging from telehealth visits to online platforms and mobile applications, will also be explored. We then evaluate the ways in which machine learning and artificial intelligence-driven algorithms are being utilized to address gaps in lipid management. From an organizational perspective, we trace the redesign of medical practices to incorporate a multidisciplinary team model of care, recognizing that atherosclerotic cardiovascular disease risk is multifaceted and requires a comprehensive approach. Finally, we anticipate the future of dyslipidemia management, assessing the many ways in which atherosclerotic cardiovascular disease burden can be reduced on a population-wide scale.

Engineering antigen-presenting cells for immunotherapy of autoimmunity.

Autoimmune diseases are burdensome conditions that affect a significant fraction of the global population. The hallmark of autoimmune disease is a host's immune system being licensed to attack its tissues based on specific antigens. There are no cures for autoimmune diseases. The current clinical standard for treating autoimmune diseases is the administration of immunosuppressants, which weaken the immune system and reduce auto-inflammatory responses. However, people living with autoimmune diseases are subject to toxicity, fail to mount a sufficient immune response to protect against pathogens, and are more likely to develop infections. Therefore, there is a concerted effort to develop more effective means of targeting immunomodulatory therapies to antigen-presenting cells, which are involved in modulating the immune responses to specific antigens. In this review, we highlight approaches that are currently in development to target antigen-presenting cells and improve therapeutic outcomes in autoimmune diseases.

U.S. Filipino Adults Have Elevated Prevalence of Hypertension Across the Adult Lifespan: Findings From a Cross-Sectional Electronic Health Record Study.

Introduction: The prevalence of hypertension increases with age and differs by race and ethnicity. Among U.S. Asian adults, prevalence is higher for Filipino adults than for other major Asian subgroups, but whether this disparity exists across the adult lifespan is unknown. This study examined hypertension prevalence by age decade, comparing Filipino adults with South Asian, Chinese, Black, Hispanic, and White adults. Methods: This cross-sectional study used 2015-2016 electronic health record data from a Northern California integrated healthcare delivery system for 1,839,603 adults aged 30-79 years, including 128,124 Filipino adults. Hypertension was defined by diagnosis codes. Sex-specific prevalence was calculated by race and ethnicity overall and by 10-year age decade from ages 30-39 years to 70-79 years. The prevalence of hypertension among 5 racial and ethnic groups was compared within each decade (with Filipino as the reference), adjusting for age, English language, diabetes, smoking, and weight category. Results: Decade-specific prevalence of hypertension among Filipino men and women, respectively, was 9.7% and 8.5% for ages 30-39 years, 26.0% and 23.9% for ages 40-49 years, 45.9% and 44.4% for ages 50-59 years, 65.4% and 63.9% for ages 60-69 years, and 82.1% and 82.9% for ages 70-79 years. Across all age decades, hypertension prevalence among Filipino adults largely tracked with Black adults and was much higher than among South Asian, Chinese, White, and Hispanic adults. This pattern remained after adjusting for covariates, with the largest differences observed for adults aged <60 years. Conclusions: Similar to Black adults, Filipino adults have persistently higher hypertension prevalence than South Asian, Chinese, Hispanic, and White adults across the adult lifespan. These findings underscore the importance of surveillance and prevention efforts for this high-risk Asian group beginning in early adulthood.

Polygenic risk and incident coronary heart disease in a large multiethnic cohort.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort. Methods: Participants (n = 63,070; 67 % female; 18 % non-European) without prior CHD were followed from 2007 through 12/31/2022. The association between the PRS and incident CHD was assessed using Cox regression adjusting for genetic ancestry and risk factors. Event rates were estimated by categories of PCE and by low/intermediate/high genetic risk within PCE categories; risk discrimination and net reclassification improvement (NRI) were also assessed. Results: There were 3,289 incident CHD events during 14 years of follow-up. Adjusted hazard ratio (aHR) for incident CHD per 1 SD increase in PRS was 1.18 (95 % CI:1.14-1.22), and the aHR for the upper vs lower quintile of the PRS was 1.66 (95 % CI:1.49-1.86). The association was consistent in both sexes, in European participants compared with all minority groups combined and was strongest in the first 5 years of follow-up. The increase in the C-statistic was 0.004 (0.747 vs. 0.751; p < 0.0001); the NRI was 2.4 (0.9-3.8) for the entire cohort and 9.7 (7.5-12.0) for intermediate PCE risk individuals. After incorporating high genetic risk, a further 10 percent of participants at borderline/intermediate PCE risk would be candidates for statin therapy. Conclusion: Inclusion of polygenic risk improved identification of primary prevention individuals who may benefit from more intensive risk factor modification.

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Comparison of Short-Term Health Care Utilization Between Telemedicine-Delivered vs In-Person Care Visits for Heart Failure.

Background: Patients with heart failure (HF) are a medically complex population with frequent hospitalizations. Downstream health care utilization following primary care delivered by telemedicine compared to in-person is unknown. Objectives: The purpose of this study was to understand differences in return in-person visits, emergency department (ED) encounters, and hospitalizations following a telemedicine vs an in-person primary care visit for patients with HF seen for a HF-related complaint. Methods: This was an observational study of all primary care visits for HF from January 1, 2022, to December 31, 2022, in an integrated health care delivery system. We compared 7-day in-person follow-up visits, ED visits, and hospitalizations (all-cause and HF-specific) by index visit type. Results: We included 3,902 primary care visits with a primary diagnosis of HF. Most visits utilized telephone or video visits (58.4% total; 44.9% telephone, 13.5% video). After adjustment, telephone visits were associated with more in-person follow-up visits (6.14% vs 4.20%; adjusted OR: 1.08-2.21; P < 0.05) but fewer ED visits (6.12% vs 8.07%; adjusted OR: 0.55-0.97; P < 0.05) compared to in-person visits. Most hospitalized patients (74%) had an admitting diagnosis of HF. There was no difference between 7-day all-cause hospitalization following telephone or video visits compared to in-person visits. Conclusions: Most patients used telemedicine to address HF-specific primary care concerns. Telephone visits were associated with slightly higher short-term in-person primary care follow-up but lower ED utilization. Overall, downstream ED visits and hospitalizations were low. Telephone and video visits appear to offer safe alternatives to in-person care for HF-related primary care and are a promising health care delivery strategy.

Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution.

With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.

Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

Emergency Department Referral of Patients With Chest Pain for Noninvasive Cardiac Testing and 2-Year Clinical Outcomes.

BACKGROUND: Noninvasive cardiac testing (NICT) has been associated with decreased long-term risks of major adverse cardiac events (MACEs) among emergency department patients at high coronary risk. It is unclear whether this association extends to patients without evidence of myocardial injury on initial ECG and cardiac troponin testing. METHODS: A retrospective cohort study was conducted of patients presenting with chest pain between 2013 and 2019 to 21 emergency departments within an integrated health care system in Northern California, excluding patients with ST-segment-elevation myocardial infarction or myocardial injury by serum troponin testing. To account for confounding by indication, we grouped patient encounters by the NICT referral rate of the initially assigned emergency physician relative to local peers within discrete time periods. The primary outcome was MACE within 2 years. Secondary outcomes were coronary revascularization and MACE, inclusive of all-cause mortality. Associations between the NICT referral group (low, intermediate, or high) and outcomes were assessed using risk-adjusted proportional hazards methods with censoring for competing events. RESULTS: Among 144 577 eligible patient encounters, the median age was 58 years (interquartile range, 48-68) and 57% were female. Thirty-day NICT referral was 13.0%, 19.9%, and 27.8% in low, intermediate, and high NICT referral groups, respectively, with a good balance of baseline covariates between groups. Compared with the low NICT referral group, there was no significant decrease in the adjusted hazard ratio of MACE within the intermediate (adjusted hazard ratio, 1.08 [95% CI, 1.02-1.14]) or high (adjusted hazard ratio, 1.05 [95% CI, 0.99-1.11]) NICT referral groups. Results were similar for MACE, inclusive of all-cause mortality, and coronary revascularization, as well as subgroup analyses stratified by estimated risk (history, electrocardiogram, age, risk factors, troponin [HEART] score: percent classified as low risk, 48.2%; moderate risk, 49.2%; and high risk, 2.7%). CONCLUSIONS: Increases in NICT referrals were not associated with changes in the hazard of MACE within 2 years following emergency department visits for chest pain without evidence of acute myocardial injury. These findings further highlight the need for evidence-based guidance regarding the appropriate use of NICT in this population.

The Relationship of Cardiorespiratory Fitness, Physical Activity, and Coronary Artery Calcification to Cardiovascular Disease Events in CARDIA Participants.

AIMS: Moderate-to-vigorous-intensity physical activity (MVPA), cardiorespiratory fitness (CRF), and coronary artery calcification (CAC) are associated with cardiovascular disease (CVD) risk. While a U-shaped relationship between CRF or MVPA and CAC has been reported, the presence of CAC among highly fit individuals might be benign. We examined interactive associations of CRF or MVPA and CAC with outcomes and evaluated the relationship of CRF and MVPA to CAC incidence. METHODS: CARDIA participants with CAC assessed in 2005-06 were included (n=3,141, mean age 45). MVPA was assessed by self-report and accelerometer. CRF was estimated with a maximal graded exercise test. Adjudicated CVD events and mortality data were obtained through 2019. CAC was reassessed in 2010-11. Cox models were constructed to assess hazard ratios (HRs) for CVD, coronary heart disease (CHD), and mortality in groups defined by CAC presence/absence and lower/higher CRF or MVPA levels. Logistic models were constructed to assess associations with CAC incidence. Adjustment was made for sociodemographic and CVD risk factors. RESULTS: Relative to participants with no CAC and higher CRF, the adjusted HRs for CVD were 4.68 for CAC and higher CRF, 2.22 for no CAC and lower CRF, and 3.72 for CAC and lower CRF. For CHD, the respective HRs were 9.98, 2.28, and 5.52. For mortality, the HRs were 1.15, 1.58, and 3.14, respectively. Similar findings were observed when MVPA, measured either by self-report or accelerometer, was substituted for CRF. A robust inverse association of CRF and accelerometer-derived MVPA with CAC incidence was partly accounted for by adjusting for CVD risk factors. CONCLUSIONS: In middle-aged adults, CRF and MVPA demonstrated an inverse association with CAC incidence but did not mitigate the increased cardiovascular risk associated with CAC, indicating that CAC is not benign in individuals with higher CRF or MVPA levels.

This study explored the relationship between physical fitness, physical activity, and coronary artery calcification (CAC) in predicting heart disease risk. CAC is the build-up of calcium deposits in the coronary arteries, indicating the presence of atherosclerosis. Involving approximately 3,000 adults with an average age of 45, the study measured physical activity through self-report and accelerometer, fitness via treadmill tests, and CAC at two time points, five years apart. Being fit and active was associated with a lower chance of developing new CAC. Similarly, higher fitness and physical activity levels were associated with a lower risk of experiencing heart disease events and death over 13 years of follow-up. In contrast, the presence of CAC strongly predicted elevated heart disease risk and death. Furthermore, having CAC eliminated the heart health benefits of being physically active or fit. The study concludes that while being fit and active is beneficial, CAC remains a serious risk factor for heart disease, even in individuals with higher fitness and physical activity levels. In middle-aged adults, being aerobically fit and physically active is associated with an overall benefit regarding heart disease events and mortality.Despite this, having CAC significantly increases the risk of heart disease events, even for those who are fit and active.

Identification and Characterization of HIRIP3 as a Histone H2A Chaperone.

HIRIP3 is a mammalian protein homologous to the yeast H2A.Z deposition chaperone Chz1. However, the structural basis underlying Chz's binding preference for H2A.Z over H2A, as well as the mechanism through which Chz1 modulates histone deposition or replacement, remains enigmatic. In this study, we aimed to characterize the function of HIRIP3 and to identify its interacting partners in HeLa cells. Our findings reveal that HIRIP3 is specifically associated in vivo with H2A-H2B dimers and CK2 kinase. While bacterially expressed HIRIP3 exhibited a similar binding affinity towards H2A and H2A.Z, the associated CK2 kinase showed a notable preference for H2A phosphorylation at serine 1. The recombinant HIRIP3 physically interacted with the H2A αC helix through an extended CHZ domain and played a crucial role in depositing the canonical core histones onto naked DNA. Our results demonstrate that mammalian HIRIP3 acts as an H2A histone chaperone, assisting in its selective phosphorylation by Ck2 kinase at serine 1 and facilitating its deposition onto chromatin.

Pilot trial of an electronic decision support to improve care for emergency department patients with acute heart failure.

AIMS: Emergency department (ED) providers play an important role in the management of patients with acute heart failure (AHF). We present findings from a pilot study of an electronic decision support that includes personalized risk estimates using the STRIDE-HF risk tool and tailored recommendations for initiating guideline directed medical therapy (GDMT) among appropriate patients. METHODS: Among ED patients treated for AHF who were discharged from the ED or the ED-based observation unit in two EDs from 1 January 2023 to 31 July 2023, we assess prescriptions to the four classes of GDMT at two intervals: (1) ED arrival and (2) ED discharge. Specifically, we report active prescriptions for beta-blockers (BBs), renin-angiotensin receptor system inhibitors (RASis), sodium-glucose transport protein 2 inhibitors (SGLT2is) and mineralocorticoid receptor antagonists (MRA) among patients with reduced ejection fraction (HFrEF) and mildly reduced (HFmrEF). Second, we describe rates of 30-day serious adverse events (SAE) (death, cardiopulmonary resuscitation, balloon-pump insertion, intubation, new dialysis, myocardial infarction or coronary revascularization) among patients predicted to be very low risk by STRIDE-HF and discharged home. RESULTS: Among 234 discharged patients, 55% were female and 76% were non-White. We found 51 (21.8%), 21 (9.0%) and 126 (53.8%) had HFrEF, HFmEF and HFpEF, respectively, while 36 (15.4%) were missing EF, and 51 (22%) were very low risk, 82 (35%) were low risk, 60 (26%) were medium risk and 41 (18%) were high risk. Among HFrEF patients, 68.6%, 66.7%, 25.5% and 19.6% were on a RASi, BB, SGLT2i and MRA, respectively, at ED arrival, while 42.9%, 66.7%, 14.3% and 4.8% of HFmrEF patients were on a RASi, BB, SGLT2i and MRA, respectively. Among patients with HFpEF, only 6 (4.8%) were on an SGLT2i at ED arrival. The most prescribed new medication at ED discharge was an SGLT2i, with a nearly 10% increase in the proportion of patients with an active prescription for SGLT2i at ED discharge among HFrEF and HFmEF patients. We observed no 30-day SAE among the 51 patients predicted to be very low risk and discharged home. CONCLUSIONS: Ongoing treatment with GDMT at ED arrival was sub-optimal. Initiation among appropriate patients at discharge may be feasible and safe.

Synthesis of biocomposites from microalgal peptide incorporated polycaprolactone/ κ- carrageenan nanofibers and their antibacterial and wound healing property.

Antimicrobial peptides (AMPs) are promising novel agents for targeting a wide range of pathogens. In this study, microalgal peptides derived from native microalgae were incorporated into polycaprolactone (PCL) with ƙ-Carrageenan (ƙ-C) forming nanofibers using the electrospinning method. The peptides incorporated in the nanofibers were characterized by fourier infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy (SEM), and contact angle measurement. The results showed that peptides with molecular weights < 10 kDa, when loaded into nanofibers, exhibited lower wettability. The SEM analysis revealed a thin, smooth, interconnected bead-like structures. The antimicrobial activity of the electrospun nanofibers was evaluated through disc diffusion, and minimum inhibitory activity against Escherichia coli (MTTC 443), and Staphylococcus aureus (MTTC 96), resulting in zones of inhibition of 24 ± 0.5 mm and 14 ± 0.5 mm, respectively. The in vitro biocompatibility of the synthesized nanofibers was confirmed using in HEK 293 cell lines with an increased cell viability. Interestingly, the fibers also exhibited a significant wound-healing properties when used in vitro scratch assays. In conclusion, algal peptides incorporated with PCL/ ƙ-C were found to exhibit antimicrobial and biocompatible biomaterials for wound healing applications.

UHRF1 poly-auto-ubiquitination induced by the anti-cancer drug, thymoquinone, is involved in the DNA repair machinery recruitment.

DNA methylation is one of the most important epigenetic mark involved in many physiologic cellular processes and pathologies. During mitosis, the transmission of DNA methylation patterns from a mother to the daughter cells is ensured through the action of the Ubiquitin-like, containing PHD and RING domains, 1/DNA methyltransferase 1 (UHRF1/DNMT1) tandem. UHRF1 is involved in the silencing of many tumor suppressor genes (TSGs) via mechanisms that remain largely to be deciphered. The present study investigated the role and the regulation of UHRF1 poly-ubiquitination induced by thymoquinone, a natural anti-cancer drug, known to enhance or re-activate the expression of TSGs. We found that the auto-ubiquitination of UHRF1, induced by TQ, is mediated by reactive oxygen species, and occurs following DNA damage. We demonstrated that the poly-ubiquitinated form of UHRF1 is K63-linked and can still silence the tumor suppressor gene p16INK4A/CDKN2A. We further showed that TQ-induced auto-ubiquitination is mediated via the activity of Tip60. Since this latter is known as a nuclear receptor co-factor, we investigated if the glucocorticoid receptor (GR) might be involved in the regulation of UHRF1 ubiquitination. Activation of the GR, with dexamethasone, did not influence auto-ubiquitination of UHRF1. However, we could observe that TQ induced a K48-linked poly-ubiquitination of GR, probably involved in the proteosomal degradation pathway. Mass-spectrometry analysis of FLAG-HA-tagged UHRF1 identified UHRF1 partners involved in DNA repair and showed that TQ increased their association with UHRF1, suggesting that poly-ubiquitination of UHRF1 is involved in the DNA repair process. We propose that poly-ubiquitination of UHRF1 serves as a scaffold to recruit the DNA repair machinery at DNA damage sites.

Associations of cannabis use and body mass index-The Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND: With increasing use of cannabis, we need to know if cannabis use and Body Mass Index (BMI) are associated. METHODS: The Coronary Artery Risk Development in Young Adults Study followed Black and White adults over 30 years with assessments every 2 to 5 years in four centers in the USA. We assessed self-reported current and computed cumulative cannabis exposure at every visit, and studied associations with BMI, adjusted for relevant covariables in mixed longitudinal models. We also applied marginal structural models (MSM) accounting for the probability of having stopped cannabis over the last 5 years. RESULTS: At the Year 30 visit, 1,912 (58 %) identified as women and 1,600 (48 %) as Black, mean age was 56 (SD 2) years. While 2,849 (85 %) had ever used cannabis, 479 (14 %) currently used cannabis. Overall, participants contributed to 35,882 individual visits over 30 years. In multivariable adjusted models, mean BMI was significantly lower in daily cannabis users (26.6 kg/m2, 95 %CI 26.3 to 27.0) than in participants without current use (27.7 kg/m2, 95 %CI 27.5 to 27.9, p < 0.001). Cumulative cannabis use was not associated with BMI. The MSM showed no change in BMI when stopping cannabis use over a 5-year period (ß=0.2 kg/m2 total, 95 %CI -0.2 to 0.6). CONCLUSIONS: Current cannabis use was associated with lower BMI, but cumulative cannabis use and cessation were not. This suggests that recreational cannabis use may not lead to clinically relevant changes in BMI and that the association between current cannabis use and lower BMI is likely due to residual confounding.

Diet quality and cardiovascular disease risk among breast cancer survivors in the Pathways Study.

BACKGROUND: Women with breast cancer are at higher risk of cardiovascular disease (CVD) compared with women without breast cancer. Whether higher diet quality at breast cancer diagnosis lowers this risk remains unknown. We set out to determine if higher diet quality at breast cancer diagnosis was related to lower risk of CVD and CVD-related death. METHODS: This analysis included 3415 participants from the Pathway Study, a prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California between 2005 and 2013 and followed through December 31, 2021. Scores from 5 diet quality indices consistent with healthy eating were obtained at the time of breast cancer diagnosis. Scores were categorized into ascending quartiles of concordance for each diet quality index, and multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. P values were 2-sided. RESULTS: The Dietary Approaches to Stop Hypertension diet quality index was associated with lower risk of heart failure (HR = 0.53, 95% CI = 0.33 to 0.87; Ptrend = .03), arrhythmia (HR = 0.77, 95% CI = 0.62 to 0.94; Ptrend = .008), cardiac arrest (HR = 0.77, 95% CI = 0.61 to 0.96; Ptrend = .02), valvular heart disease (HR = 0.79, 95% CI = 0.64 to 0.98; Ptrend = .046), venous thromboembolic disease (HR = 0.75, 95% CI = 0.60 to 0.93; Ptrend = .01), and CVD-related death (HR = 0.70, 95% CI = 0.50 to 0.99; Ptrend = .04), when comparing the highest with lowest quartiles. Inverse associations were also found between the healthy plant-based dietary index and heart failure (HR = 0.60, 95% CI = 0.39 to 0.94; Ptrend = .02), as well as the alternate Mediterranean dietary index and arrhythmia (HR = 0.74, 95% CI = 0.60 to 0.93; Ptrend = .02). CONCLUSION: Among newly diagnosed breast cancer patients, higher diet quality at diagnosis was associated with lower risk of CVD events and death.