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Currently, research in youth soccer consists of methodological choices that can raise activity volumes and exercise intensity to promote proper training for youth soccer demands. Therefore, the present cluster randomised trial aims to evaluate the effects of the dynamic-ecological approach on the physical performance parameters compared with a traditional one in a group of sub-elite U13 players. Thirty-five male children (age 12.16 ± 0.55 years; weight 45.59 ± 7.15 kg; height 145.5 ± 4.2 cm; BMI 15.8 ± 2.1 kg·m -2 ) were recruited for this trial from two teams belonging to sub-elite soccer schools and randomly assigned to a dynamic-ecological approach (DEA) or a traditional training (TTG) group. The training program lasted six weeks and consisted of 18 training sessions of 90 min each (3 sessions per week). The sample was evaluated by the standing long jump (SLJ), hop test (HT), 10 m sprint (10 m), 10 × 5 m shuttle run test (SRT), and leg raise test (LR). The DEA group showed significantly higher results in the SLJ ( p < 0.001), HT left leg ( p < 0.001), 10 m sprint ( p < 0.001), and SRT ( p < 0.001). In conclusion, the dynamic-ecological approach provides higher performance adaptations. Therefore, this approach can be considered a suitable method to optimise pre-pubertal player training, mainly when no fitness or strength coach is available.

Testing for coronavirus disease 2019 is critical in controlling the pandemic all over the world. Diagnosis of severe acute respiratory syndrome coronavirus-2 infection is based on real-time polymerase chain reaction performed on nasopharyngeal swab. If not adequately performed, the viral specimen collection can be painful and lead to complications. We present a complication occurred during a nasopharyngeal swab collection performed in a noncooperative patient where the plastic shaft of the swab fractured during the procedure, resulting in swab tip retention deep into the nasal cavity. The foreign body was found endoscopically, stuck between the nasal septum and the superior turbinate tail at the upper level of the left choana and removed under general anesthesia in a negative pressure operating room with the health care personnel wearing personal protective equipment. Unpleasant complications like the one described can happen when the swab is collected without the necessary knowledge of nasal anatomy or conducted inappropriately, especially in noncooperative patients. Moreover, the design of currently used viral swabs may expose to accidental rupture, with risk of foreign body retention in the nasal cavities. In such cases, diagnosis and treatment are endoscopy-guided procedures performed in an adequate setting to minimize the risk of spreading of the pandemic.

Treatment for individuals with fibromyalgia syndrome (FMS) is complex and is not always accessible to those who could benefit. The aim of this study was to conduct a preliminary evaluation of a mobile-app-delivered, cognitive behavioral treatment (CBT)-based intervention in helping adults self-manage fibromyalgia symptoms. A total of 100 adults with FMS ( M [SD] age = 49.81, [9.99] years; 94% women) were given access to the digital treatment program and downloaded the app. Pain severity, anxiety symptoms, depression symptoms, fatigue, and sleep quality were assessed at pre-treatment, post-treatment, and 3-month follow-up. Fifty-three of the potential participants completed the 47-day treatment. Data showed significant improvements in pain severity ( p = 0.007, d = 0.43), anxiety ( p = 0.011, d = 0.40) and depressive symptoms ( p = 0.001, d = 0.50) from pre-treatment to post-treatment. The effect sizes associated with app use are consistent with improvements seen in previously published clinical trials of CBT for FMS. Improvements were generally maintained, although there was some decrease in the outcomes from post-treatment to the 3-month follow-up. Most participants reported that they were very satisfied with the app. The use of the app was associated with similar levels of improvements found with in-person CBT treatment for FMS. Research to evaluate the effectiveness of the app in a controlled trial is warranted.

The Omicron variant of SARS-CoV-2 infected many vaccinated and convalescent individuals 1-3 . Despite the reduced protection from infection, individuals who received three doses of an mRNA vaccine were highly protected from more serious consequences of infection 4 . Here we examine the memory B cell repertoire in a longitudinal cohort of individuals receiving three mRNA vaccine doses 5,6 . We find that the third dose is accompanied by an increase in, and evolution of, receptor-binding domain (RBD)-specific memory B cells. The increase is due to expansion of memory B cell clones that were present after the second dose as well as the emergence of new clones. The antibodies encoded by these cells showed significantly increased potency and breadth when compared with antibodies obtained after the second dose. Notably, the increase in potency was especially evident among newly developing clones of memory cells, which differed from persisting clones in targeting more conserved regions of the RBD. Overall, more than 50% of the analysed neutralizing antibodies in the memory compartment after the third mRNA vaccine dose neutralized the Omicron variant. Thus, individuals receiving three doses of an mRNA vaccine have a diverse memory B cell repertoire that can respond rapidly and produce antibodies capable of clearing even diversified variants such as Omicron. These data help to explain why a third dose of a vaccine that was not specifically designed to protect against variants is effective against variant-induced serious disease., (© 2022. The Author(s).)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During that time, memory B cells express increasingly broad and potent antibodies that are resistant to mutations found in variants of concern 1 . As a result, vaccination of coronavirus disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines produces high levels of plasma neutralizing activity against all variants tested 1,2 . Here we examine memory B cell evolution five months after vaccination with either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) mRNA vaccine in a cohort of SARS-CoV-2-naive individuals. Between prime and boost, memory B cells produce antibodies that evolve increased neutralizing activity, but there is no further increase in potency or breadth thereafter. Instead, memory B cells that emerge five months after vaccination of naive individuals express antibodies that are similar to those that dominate the initial response. While individual memory antibodies selected over time by natural infection have greater potency and breadth than antibodies elicited by vaccination, the overall neutralizing potency of plasma is greater following vaccination. These results suggest that boosting vaccinated individuals with currently available mRNA vaccines will increase plasma neutralizing activity but may not produce antibodies with equivalent breadth to those obtained by vaccinating convalescent individuals., (© 2021. The Author(s).)

These Lipid Association of India (LAI) recommendations refer to specific patient populations. They follow the previously published LAI part 1 recommendations. These part 2 LAI recommendations focus on specific patient groups. These include patients with heart failure, chronic kidney disease, non-alcoholic fatty liver disease, cerebrovascular disease, thyroid disorders, inflammatory joint diseases, familial hypercholesterolaemia and human immunodeficiency virus infection. We also consider women, the elderly and post-transplantation patients. The current recommendations are based, as much as possible, on available data from Indian populations. [ABSTRACT FROM AUTHOR]

More than one year after its inception, the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains difficult to control despite the availability of several working vaccines. Progress in controlling the pandemic is slowed by the emergence of variants that appear to be more transmissible and more resistant to antibodies 1,2 . Here we report on a cohort of 63 individuals who have recovered from COVID-19 assessed at 1.3, 6.2 and 12 months after SARS-CoV-2 infection, 41% of whom also received mRNA vaccines 3,4 . In the absence of vaccination, antibody reactivity to the receptor binding domain (RBD) of SARS-CoV-2, neutralizing activity and the number of RBD-specific memory B cells remain relatively stable between 6 and 12 months after infection. Vaccination increases all components of the humoral response and, as expected, results in serum neutralizing activities against variants of concern similar to or greater than the neutralizing activity against the original Wuhan Hu-1 strain achieved by vaccination of naive individuals 2,5-8 . The mechanism underlying these broad-based responses involves ongoing antibody somatic mutation, memory B cell clonal turnover and development of monoclonal antibodies that are exceptionally resistant to SARS-CoV-2 RBD mutations, including those found in the variants of concern 4,9 . In addition, B cell clones expressing broad and potent antibodies are selectively retained in the repertoire over time and expand markedly after vaccination. The data suggest that immunity in convalescent individuals will be very long lasting and that convalescent individuals who receive available mRNA vaccines will produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants., (© 2021. The Author(s).)

Byline: Sunandan. Sikdar, Vaibhav. Sahni, Amit. Miglani, M. Daga Sir, Seizures are sometimes seen in pregnancy. However, rarely do we come across an underlying etiology, which is at least partially [...]

Tetrahydroisoquinoline (THIQ) is a key structural component in many biologically active molecules including natural products and synthetic pharmaceuticals. Here, we report on the use of transition-metal mediated [2 + 2 + 2] cyclotrimerisation of alkynes to generate tricyclic THIQs with potential to selectively inhibit AKR1C3., (This journal is © The Royal Society of Chemistry 2019.)

Background: Ailanthone (Aila) is a natural active compound isolated from the Ailanthus altissima, which has been shown to possess an "in vitro" growth-inhibitory effect against several cancer cell lines. Advanced bladder cancer is a common disease characterized by a frequent onset of resistance to cisplatin-based therapy. The cisplatin (CDDP) resistance is accompanied by an increase in Nrf2 protein expression which contributes to conferring resistance. Recently, we demonstrated a cross-talk between Nrf2 and YAP. YAP has also been demonstrated to play an important role in chemoresistance of bladder cancer., Purpose: We analyzed the antitumor effect of Aila in sensitive and CDDP-resistant bladder cancer cells and the molecular mechanisms involved in Aila activity., Study Design: Sensitive and CDDP-resistant 253J B-V and 253J bladder cancer cells, intrinsically CDDP-resistant T24 bladder cancer cells and HK-2 human renal cortex cells were used. Cells were treated with diverse concentrations of Aila and proliferation, cell cycle, apoptosis and gene expressions were determined., Methods: Aila toxicity and proliferation were determined by MTT and colony forming methods, respectively. Cell cycle was determined by cytofluorimetric analysis through PI staining method. Apoptosis was detected using Annexin V and PI double staining followed by quantitative flow cytometry. Expressions of Nrf2, Yap, c-Myc, and house-keeping genes were determined by western blot with specific antibodies. Cell migration was detected by wound healing and Boyden chamber analysis., Results: Aila inhibited the growth of sensitive and CDDP-resistant bladder cancer cells with the same effectiveness. On the contrary, the growth of HK-2 cells was only slightly reduced by Aila. Cell cycle analysis revealed an accumulation of Aila-treated bladder cancer cells in the G0/G1 phase. Interestingly, Aila strongly reduced Nrf2 expression in these cell lines. Moreover, Aila significantly reduced YAP, and c-Myc protein expression. The random and the oriented migration of bladder cancer cells were strongly inhibited by Aila treatment, in particular in CDDP-resistant cells., Conclusion: Aila inhibited proliferation and invasiveness of bladder cancer cells. Its high effectiveness in CDDP resistant cells could be related to the inhibition of Nrf2, YAP, and c-Myc expressions. Aila could represent a new tool to treating CDDP-resistant bladder cancers., (Copyright © 2018. Published by Elsevier GmbH.)

Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age. Since the involvement and the role of lipid peroxidation-derived aldehydes, particularly of 4-hydroxynonenal (HNE), in neurodegenerations, inflammation, and cancer, has been discussed in several excellent recent reviews, in the present one we focus on the involvement of reactive aldehydes in other age-related disorders: osteopenia, sarcopenia, immunosenescence and myelodysplastic syndromes. In these aging-related disorders, characterized by increases of oxidative stress, both HNE and malondialdehyde (MDA) play important pathogenic roles. These aldehydes, and HNE in particular, can form adducts with circulating or cellular proteins of critical functional importance, such as the proteins involved in apoptosis in muscle cells, thus leading to their functional decay and acceleration of their molecular turnover and functionality. We suggest that a major fraction of the toxic effects observed in age-related disorders could depend on the formation of aldehyde-protein adducts. New redox proteomic approaches, pinpointing the modifications of distinct cell proteins by the aldehydes generated in the course of oxidative stress, should be extended to these age-associated disorders, to pave the way to targeted therapeutic strategies, aiming to alleviate the burden of morbidity and mortality associated with these disturbances., Competing Interests: The authors declare no conflict of interest.

Background: Assessment of an age of an individual whether living or dead through teeth is one of the most reliable and simple method to calculate age than skeletal remains especially when they are in poor conditions., Objectives: The study was carried out with aim of (i) to evaluate reliability of dental age assessment through two different methods for adults i.e. tooth coronal index and pulp/tooth ratio using digital panoramic radiographs and (ii) to compare these methods for their accuracy in age determination., Materials and Methods: The digital panoramic radiographs of 180 subjects of Chhattisgarh aged 15-70 years were selected for the study. The measurements were performed on the JPEG images of selected panoramic radiographs by using Adobe Acrobat 7.0 professional software. For tooth coronal index (TCI), height of the crown i.e. coronal height (CH) and the height of the coronal pulp cavity i.e. coronal pulp cavity height (CPCH) of mandibular second premolars and first molars was measured in millimeter (mm) and then TCI was calculated for each tooth and calculated age was compared with chronological age. For pulp/tooth ratio, the measurements of pulp chamber height (PCH) and crown root trunk height (CRTH) were performed on the mandibular first and second molar teeth, the pulp chamber crown root trunk height ratios (PCTHR) of selected tooth were calculated. The acquired data were subjected to Pearson correlation test, unpaired t test and Analysis of Variance (ANOVA) analysis., Results: Results suggested that TCI (mandibular first molar r=-0.178), second premolar (r=-0.187) and PCTHR(mandibular first molar r=-0.921, second molar r=-0.901) correlated negatively with chronological age suggesting decrease in size of pulp cavity. Mandibular first molar was found to be most reliable tooth to estimate dental age., Conclusion: The study showed that both PCTHR and TCI have negative association with chronological age. PCTHR showed slightly higher negative correlation and proved as a better tool for age estimation than TCI. Statistically significant differences were observed between chronological and calculated age by both methods thus emphasizing the need for future clinical trials., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts, which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity., Competing Interests: Conflict of interest: The authors declare there is no conflict of interest.

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations.

Objective: To investigate the relationship of psychosocial factors (lack of social support, stress and subjective well-being) and personality traits with myocardial infarction (MI). Materials and Methods: A case-control study involving 100 cases and 100 matched controls was conducted in Lok Nayak Hospital, New Delhi. Results: Stress over 1 year was significantly higher in cases (P < 0.001). However, difference was not significant when scores of social support (P = 0.2), Presumptive Stressful Life Event (PSLE) over lifetime (P = 0.058) and subjective well-being (P = 0.987) were compared. MI was significantly associated with hyperactive (P < 0.001), dominant (P = 0.03), egoistic (P < 0.001) and introvert (P < 0.001) personalities. Conclusion: Certain personality traits and recent stress may be important risk factors of MI, especially in Indians. The finding may have implications on the preventive strategies planned for MI patients. [ABSTRACT FROM AUTHOR]

Heat shock 60 kDa protein 1 (HSP60) is a chaperone and stress response protein responsible for protein folding and delivery of endogenous peptides to antigen-presenting cells and also a target of autoimmunity implicated in the pathogenesis of atherosclerosis. By two-dimensional electrophoresis and mass spectrometry, we found that exposure of human promyelocytic HL-60 cells to a nontoxic concentration (10 μM) of 4-hydroxy-2-nonenal (HNE) yielded a HSP60 modified with HNE. We also detected adducts of HNE with putative uncharacterized protein CXorf49, the product of an open reading frame identified in various cell and tissue proteomes. Moreover, exposure of human monocytic THP-1 cells differentiated with phorbol 12-myristate 13-acetate to 10 μM HNE, and to light density lipoprotein modified with HNE (HNE-LDL) or by copper-catalyzed oxidation (oxLDL), but not to native LDL, stimulated the formation of HNE adducts with HSP60, as detected by immunoprecipitation and western blot, well over basal levels. The identification of HNE-HSP60 adducts outlines a framework of mutually reinforcing interactions between endothelial cell stressors, like oxLDL and HSP60, whose possible outcomes, such as the amplification of endothelial dysfunction, the spreading of lipoxidative damage to other proteins, such as CXorf49, the activation of antigen-presenting cells, and the breaking of tolerance to HSP60 are discussed.

Coronavirus disease 2019 (COVID-19) represents the novel respiratory infectious disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by rapid spread throughout the world. Reactive oxygen species (ROS) account for cellular metabolic by-products, and excessive ROS accumulation can induce oxidative stress due to insufficient endogenous antioxidant ability. In the case of oxidative stress, ROS production exceeds the cellular antioxidant capacity, thus leading to cell death. SARS-CoV-2 can activate different cell death pathways in the context of infection in host cells, such as neutrophil extracellular trap (NET)osis, ferroptosis, apoptosis, pyroptosis, necroptosis and autophagy, which are closely related to ROS signalling and control. In this review, we comprehensively elucidated the relationship between ROS generation and the death of host cells after SARS-CoV-2 infection, which leads to the development of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Introduction: Ferroptosis is a new type of cell death characterized by lipid peroxidation and iron dependency, representing an emerging disease regulation mechanism. The limited understanding of ferroptosis in peripheral nerve injury (PNI) complicates the management of such injuries. Mitochondrial dysfunction, which contributes to ferroptosis, further exacerbates the challenges of peripheral nerve repair Methods: In this study, we established an in vitro model of Schwann cells model treated with TBHP and an in vivo sciatic nerve crush injury model in rats. These models were used to investigate the effects of fibroblast growth factor 21 (FGF21) on PNI, both in vitro and in vivo, and to explore the potential mechanisms linking injury-induced ferroptosis and mitochondrial dysfunction. Results: Our findings reveal that PNI triggers abnormal accumulation of lipid reactive oxygen species (ROS) and inactivates mitochondrial respiratory chain complex III, leading to mitochondrial dysfunction. This dysfunction catalyzes the oxidation of excessive polyunsaturated fatty acids, resulting in antioxidant imbalance and loss of ferroptosis suppressor protein 1 (FSP1), which drives lipid peroxidation. Additionally, irregular iron metabolism, defective mitophagy, and other factors contribute to the induction of ferroptosis. Importantly, we found that FGF21 attenuates the abnormal accumulation of lipid ROS, restores mitochondrial function, and suppresses ferroptosis, thus promoting PNI repair. Notably, glutathione peroxidase 4 (GPX4), a downstream target of nuclear factor E2-related factor 2 (Nrf2), and the ERK/Nrf2 pathway are involved in the regulation of ferroptosis by FGF21. Conclusion: FGF21 promotes peripheral nerve repair by inhibiting ferroptosis caused by mitochondrial dysfunction. Therefore, targeting mitochondria and ferroptosis represents a promising therapeutic strategy for effective PNI repair. [ABSTRACT FROM AUTHOR]

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology’s role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated that naringenin possesses lipid-lowering effects; however, the underlying mechanisms, particularly its specific molecular targets, remain uncertain. Methods: Using bioinformatics, three traditional Chinese medicine databases and one human disease database were integrated to establish two naringenin-target-hyperlipidemia modules: naringenin-oxidative stress (OS) and naringenin-lipid metabolism (LM). Data on 1,850 proteins from 1,871 genetic instruments were sourced from seven previous studies. Using Mendelian randomization based on data from the Integrative Epidemiology Unit genome-wide association study (case, n = 5,153; control, n = 344,069), we identified potential drug targets that were subsequently validated in the UK Biobank (396,565 individuals) and FinnGen (412,181 individuals) cohorts. Using molecular docking and molecular dynamics simulation to verify the binding ability of naringenin and causal protein. Results: In plasma, every standard deviation increase in apolipoprotein B (APOB) was associated with an increased risk of hyperlipidemia (odds ratio [OR] = 9.37, 95% confidence interval [CI], 5.12-17.12; P = 3.58e-13; posterior probability of hypothesis 4 [PPH4] = 0.997), and the same was observed for proprotein convertase subtilisin/kexin type 9 (OR = 1.81, 95% CI, 1.51-2.16; P = 6.87e-11; PPH4 = 1) and neurocan (OR = 2.34, 95% CI, 1.82-3.01; P = 4.09e-11; PPH4 = 0.932). The intersection of two modules and Mendelian randomization result identified APOB as a key regulatory target of naringenin in the treatment of hyperlipidemia. The binding energy between naringenin and APOB was determined to be -7.7 kcal/mol. Additionally, protein-protein interactions and protein-disease networks were analyzed to uncover potential connections between proteins and hyperlipidemia. Conclusion: This Mendelian randomization-based combined analysis offers a robust framework for elucidating the pharmacological effects of naringenin and identifying candidate proteins for further investigation in the context of hyperlipidemia treatment. [ABSTRACT FROM AUTHOR]

Muscle wasting is a serious complication in heart failure patients. Oxidative stress and inflammation are implicated in the pathogenesis of muscle wasting. Oxidative stress leads to the formation of toxic lipid peroxidation products, such as 4-hydroxy-2-nonenal (HNE), which covalently bind with proteins and DNA and activate atrophic pathways. Whether the formation of lipid peroxidation products and metabolic pathways that remove these toxic products are affected during heart failure-associated skeletal muscle wasting has never been studied. Male C57BL/6J mice were subjected to sham and transverse aortic constriction (TAC) surgeries for 4, 8 or 14 weeks. Different skeletal muscle beds were weighed, and the total cross-sectional area of the gastrocnemius muscle was measured via immunohistochemistry. Muscle function and muscle stiffness were measured by a grip strength meter and atomic force microscope, respectively. Atrophic and inflammatory marker levels were measured via qRT‒PCR. The levels of acrolein and HNE-protein adducts, aldehyde-removing enzymes, the histidyl dipeptide-synthesizing enzyme carnosine synthase (CARNS), and amino acid transporters in the gastrocnemius muscle were measured via Western blotting and qRT‒PCR. Histidyl dipeptides and histidyl dipeptide aldehyde conjugates in the Gastrocnemius and soleus muscles were analyzed by LC/MS–MS. Body weight, gastrocnemius muscle and soleus muscle weights and the total cross-sectional area of the gastrocnemius muscle were decreased after 14 weeks of TAC. Heart weight, cardiac function, grip strength and muscle stiffness were decreased in the TAC-operated mice. Expression of the atrophic and inflammatory markers Atrogin1 and TNF-α, respectively, was increased ~ 1.5–2fold in the gastrocnemius muscle after 14 weeks of TAC (p < 0.05 and p = 0.004 vs sham). The formation of HNE and acrolein protein adducts was increased, and the expression of the aldehyde-removing enzyme aldehyde dehydrogenase (ALDH2) was decreased in the gastrocnemius muscle of TAC mice. Carnosine (sham: 5.76 ± 1.3 vs TAC: 4.72 ± 0.7 nmol/mg tissue, p = 0.04) and total histidyl dipeptide levels (carnosine and anserine; sham: 11.97 ± 1.5 vs TAC: 10.13 ± 1.4 nmol/mg tissue, p < 0.05) were decreased in the gastrocnemius muscle of TAC mice. Depletion of histidyl dipeptides diminished the aldehyde removal capacity of the atrophic gastrocnemius muscle. Furthermore, CARNS and TAUT protein expression were decreased in the atrophic gastrocnemius muscle. Our data reveals that reduced expression of ALDH2 and depletion of histidyl dipeptides in the gastrocnemius muscle during heart failure leads to the accumulation of toxic aldehydes and might contribute to muscle wasting. [ABSTRACT FROM AUTHOR]

Individuals diagnosed with Parkinson's disease (PD) often exhibit heightened susceptibility to cardiac dysfunction, reflecting a complex interaction between these conditions. The involvement of mitochondrial dysfunction in the development and progression of cardiac dysfunction and PD suggests a plausible commonality in some aspects of their molecular pathogenesis, potentially contributing to the prevalence of cardiac issues in PD. Mitochondria, crucial organelles responsible for energy production and cellular regulation, play important roles in tissues with high energetic demands, such as neurons and cardiac cells. Mitochondrial dysfunction can occur in different and non-mutually exclusive ways; however, some mechanisms include alterations in mitochondrial dynamics, compromised bioenergetics, biogenesis deficits, oxidative stress, impaired mitophagy, and disrupted calcium balance. It is plausible that these factors contribute to the increased prevalence of cardiac dysfunction in PD, suggesting mitochondrial health as a potential target for therapeutic intervention. This review provides an overview of the physiological mechanisms underlying mitochondrial quality control systems. It summarises the diverse roles of mitochondria in brain and heart function, highlighting shared pathways potentially exhibiting dysfunction and driving cardiac comorbidities in PD. By highlighting strategies to mitigate dysfunction associated with mitochondrial impairment in cardiac and neural tissues, our review aims to provide new perspectives on therapeutic approaches. [ABSTRACT FROM AUTHOR]

For a sustainable ecology, slaughterhouse sludge must be managed effectively in preview of the parasitic or coliforms' spill over to the community. In order to determine the effectiveness of a customized biological decomposer solution in lowering the parasitic eggs and coliform bacteria, three composting units (Unit 1, Unit 2, and Unit 3) were treated with its different amounts. Over a period of 60 days, pH, temperature, humidity, number of the parasitic eggs per gram (EPG) of faecal material, viability of eggs, and coliform counts were evaluated. By the fifth day of the composting process, pH had significantly (P < 0.05) increased across all the treatments and then decreased gradually. Also on the 5th day, all three units entered the thermophilic range (> 45 °C), which persisted for 20 days for Unit 3 and 15 days for Units 1 and 2. Humidity levels initially increased significantly (P < 0.05) in all three units (Unit 3 = 71%, Unit 2 = 64%, and Unit 1 = 55%) but then gradually decreased. On day 5, no decrease in EPG in Unit 1 was detected; however, a non-significant (P > 0.05) 12.5% decline in EPG in Unit 2 and Unit 3 was recorded. After that, a significant (P < 0.05) reduction in EPG was observed in all the three treatments until day 25. By day 5, decreased egg viability was significantly (P < 0.05) recorded in Unit 3 (21.43%); in Unit 1 and Unit 2, the decrease was 6.25% and 14.29%, respectively. Additionally, all units showed a significant (P < 0.05) decrease in total coliforms, meeting minimum allowable limit in Unit 2 and 3 on day 10 and on day 15 in Unit 1. The most substantial reduction in faecal coliforms was observed in Unit 3 (from 2.6 log₁₀ to 1.3 log₁₀), followed by Unit 2 (from 2.6 log₁₀ to 1.5 log₁₀), and then Unit 1 (from 2.6 log₁₀ to 1.6 log₁₀). The results of this study support recommendation of advanced composting techniques to eradicate or reduce the abundance of pathogens (parasites and coliforms). Hence, we endorse the value of careful composting procedures in environment-friendly abattoir waste management and agricultural practices through creating pathogen-free, eco-friendly fertilizers to promote both agricultural and environmental sustainability. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) stands as a significant global health issue, marked by elevated occurrence and mortality statistics. Despite the availability of various treatments, including chemotherapy, radiotherapy, and targeted therapy, CRC cells often exhibit resistance to these interventions. As a result, it is imperative to identify the disease at an earlier stage and enhance the response to treatment by acquiring a deeper comprehension of the processes driving tumor formation, aggressiveness, metastasis, and resistance to therapy. The Hippo pathway plays a critical role in facilitating the initiation of tumorigenesis and frequently experiences disruption within CRC because of genetic mutations and modified expression in its fundamental constituents. Targeting upstream regulators or core Hippo pathway components may provide innovative therapeutic strategies for modulating Hippo signaling dysfunction in CRC. To advance novel therapeutic techniques for CRC, it is imperative to grasp the involvement of the Hippo pathway in CRC and its interaction with alternate signaling pathways, noncoding RNAs, gut microbiota, and the immune microenvironment. This review seeks to illuminate the function and control of the Hippo pathway in CRC, ultimately aiming to unearth innovative therapeutic methodologies for addressing this ailment. [ABSTRACT FROM AUTHOR]

Mitophagy, a selective form of autophagy, plays a crucial role in maintaining optimal mitochondrial populations, normal function, and intracellular homeostasis by monitoring and removing damaged or excess mitochondria. Furthermore, mitophagy promotes mitochondrial degradation via the lysosomal pathway, and not only eliminates damaged mitochondria but also regulates programmed cell death-associated genes, thus preventing cell death. The interaction between mitophagy and various forms of cell death has recently gained increasing attention in relation to the pathogenesis of clinical diseases, such as cancers and osteoarthritis, neurodegenerative, cardiovascular, and renal diseases. However, despite the abundant literature on this subject, there is a lack of understanding regarding the interaction between mitophagy and cell death. In this review, we discuss the main pathways of mitophagy, those related to cell death mechanisms (including apoptosis, ferroptosis, and pyroptosis), and the relationship between mitophagy and cell death uncovered in recent years. Our study offers potential directions for therapeutic intervention and disease diagnosis, and contributes to understanding the molecular mechanism of mitophagy. [ABSTRACT FROM AUTHOR]

The surge in demand for 3D MOSFETs, such as FinFETs, driven by recent technological advances, is explored in this review. FinFETs, positioned as promising alternatives to bulk CMOS, exhibit favorable electrostatic characteristics and offer power/performance benefits, scalability, and control over short-channel effects. Simulations provide insights into functionality and leakage, addressing off-current issues common in narrow band-gap materials within a CMOS-compatible process. Multiple structures have been introduced for FinFETs. Moreover, some studies on the fabrication of FinFETs using different materials have been discussed. Despite their potential, challenges like corner effects, quantum effects, width quantization, layout dependencies, and parasitics have been acknowledged. In the post-planar CMOS landscape, FinFETs show potential for scalability in nanoscale CMOS, which leads to novel structures for them. Finally, recent developments in FinFET-based sensors are discussed. In a general view, this comprehensive review delves into the intricacies of FinFET fabrication, exploring historical development, classifications, and cutting-edge ideas for the used materials and FinFET application, i.e., sensing. [ABSTRACT FROM AUTHOR]

The current work is devoted to the development of probiotic microencapsulation systems with the co-encapsulation of a plant extract, which can increase the survival of beneficial bacteria and are suitable for potential applications in the enrichment of fermented beverages based on acid whey. The encapsulation process exhibited a high level of effectiveness, achieving 83.0% for Bifidobacterium (BB), 89.2% for Stevia leaf extract (SE), and 91.3% for their combination (BB + SE). The FTIR analysis verified substantial interactions between the encapsulated agents and the polymer matrix, which enhanced the stability of the microcapsules. The BB + SE microcapsules exhibited reduced swelling and moisture content, indicating a denser structure compared to separately encapsulated BB and SE. Comparison of release kinetics of BB, SE and BB + SE loaded microcapsules showed that the combination of active agents has a quicker initial release, reaching 60% release within the first 2 h, and this value increased to 70% after 4 h. The release kinetics studies demonstrated a controlled release of active substances over 24 h. A morphology analysis shows that the surfaces of the dry microcapsules containing BB, SE, and their combination BB + SE have a porous structure. For encapsulated agents, the size of the capsules produced with BB and SE are smaller than those produced with two components (BB + SE), the sizes of which are between 760 µm and 1.1 mm. Modeling of the behavior of microcapsules in a simulated gastrointestinal tract provides information on swelling and active agents release rates as a function of pH in real biological environments. Thus, the new formulations of microcapsules with microorganisms and plant extracts have great potential for the development of fermented whey-based beverages. [ABSTRACT FROM AUTHOR]

Background: Hydrogen-rich water (HRW) has garnered significant interest within the sports and exercise science community due to its selective antioxidant properties. Despite its potential benefits, comprehensive reviews specifically addressing its effects on athletic performance are limited. This review aims to assess the impact of HRW on sports performance and explore the underlying molecular biological mechanisms, with the goal of elucidating how HRW might enhance athletic performance. Methods: This review synthesizes research on HRW by examining articles published between 1980 and April 2024 in databases such as PubMed, the Cochrane Library, Embase, Scopus, and Web of Science. Results: It highlights HRW's effects on various aspects of athletic performance, including endurance, strength, sprint times, lunge movements, countermovement jump height, and time to exhaustion. While the precise mechanisms by which HRW affects athletic performance remain unclear, this review investigates its general molecular biological mechanisms beyond the specific context of sports. This provides a theoretical foundation for future research aimed at understanding how HRW can enhance athletic performance. HRW targets the harmful reactive oxygen and nitrogen species produced during intense exercise, thereby reducing oxidative stress—a critical factor in muscle fatigue, inflammation, and diminished athletic performance. HRW helps to scavenge hydroxyl radicals and peroxynitrite, regulate antioxidant enzymes, mitigate lipid peroxidation, reduce inflammation, protect against mitochondrial dysfunction, and modulate cellular signaling pathways. Conclusions: In summary, while a few studies have indicated that HRW may not produce significant beneficial effects, the majority of research supports the conclusion that HRW may enhance athletic performance across various sports. The potential mechanisms underlying these benefits are thought to involve HRW's role as a selective antioxidant, its impact on oxidative stress, and its regulation of redox homeostasis. However, the specific molecular biological mechanisms through which HRW improves athletic performance remain to be fully elucidated. [ABSTRACT FROM AUTHOR]

Aldehyde exposure has been shown to lead to the formation of DNA damage comprising of DNA-protein crosslinks (DPCs), base adducts and interstrand or intrastrand crosslinks. DPCs have recently drawn more attention because of recent advances in detection and quantification of these adducts. DPCs are highly deleterious to genome stability and have been shown to block replication forks, leading to wide-spread mutagenesis. Cellular mechanisms to prevent DPC-induced damage include excision repair pathways, homologous recombination, and specialized proteases involved in cleaving the covalently bound proteins from DNA. These pathways were first discovered in formaldehyde-treated cells, however, since then, various other aldehydes have been shown to induce formation of DPCs in cells. Defects in DPC repair or aldehyde clearance mechanisms lead to various diseases including Ruijs-Aalfs syndrome and AMeD syndrome in humans. Here, we discuss recent developments in understanding how aldehydes form DPCs, how they are repaired, and the consequences of defects in these repair pathways. [ABSTRACT FROM AUTHOR]