Reduction Of Damage Research Articles

Curcumin Mitigates Streptozotocin-Induced Genotoxicity In Vivo by Activating P53 Protein and Inhibiting Oxidative Stress and Chromosomal Aberration.

Genotoxins are chemical constituents that damage DNA or chromosomal architecture, leading to alterations in the genetic level. Streptozotocin, a monofunctional nitrosourea derivative, is often utilized to induce diabetes mellitus in laboratory animals because of its detrimental effects on pancreatic cells. The purpose of this work was to investigate possible protective efficacy against the genotoxic effects of Streptozotocin. This study examines the potentiality of curcumin, a phytoproduct with anti-genotoxic and anti-diabetic qualities, against streptozotocin-induced chromosomal abnormalities and DNA damage. The study evaluates the possible protective efficacy of curcumin, exploring a variety of biochemical and molecular biology techniques in murine models. The experiment involves a control group, the administration of Streptozotocin (Group S), and a curcumin-pretreated STZ group (Group SC) in mice. The effects of curcumin on DNA damage and chromosomal aberrations were investigated by histopathology, immunofluorescence, evaluation of chromosomal aberrations, detection of Reactive oxygen species, cell viability analysis, and DNA laddering assay. The results demonstrated a significant reduction in DNA damage, chromosomal anomalies, and a decrease in the expression of the p53 protein in the curcumin-treated animals compared to that of STZ-treated mice. The overall results show that curcumin can reduce chromosomal aberrations and DNA damage by altering the expression of p53 repair proteins. This suggests that curcumin has a promising future as a therapeutic agent, especially when it comes to drug-induced toxicity and the development of novel therapeutics.

Long-term calorie restriction reduces oxidative DNA damage to oligodendroglia and promotes homeostatic microglia in the aging monkey brain

Calorie restriction (CR) is a robust intervention that can slow biological aging and extend lifespan. In the brain, terminally differentiated neurons and glia accumulate oxidative damage with age, reducing their optimal function. We investigated if CR could reduce oxidative DNA damage to white matter oligodendrocytes and microglia. This study utilized post-mortem brain tissue from rhesus monkeys that died after decades on a 30 % reduced calorie diet. We found that CR subjects had significantly fewer cells with oxidative damage within the corpus callosum and the cingulum bundle. Oligodendrocytes specifically showed the greatest response to CR with a robust reduction in DNA damage. Additionally, we observed alterations in microglia morphology with CR subjects having a higher proportion of ramified, homeostatic microglia and fewer pro-inflammatory, hypertrophic microglia relative to controls. Furthermore, we determined that the observed attenuation in damaged DNA occurs primarily within mitochondria. Overall, these data suggest that long-term CR can reduce oxidative DNA damage and offer a neuroprotective effect in a cell-type-specific manner in the aging monkey brain.

Dietary menhaden fish oil supplementation suppresses lipopolysaccharide-induced neuroinflammation and cognitive impairment in diabetic rats

Context Menhaden fish oil (FO) is widely recognized for inhibiting neuroinflammatory responses and preserving brain function. Nevertheless, the mechanisms of FO influencing brain cognitive function in diabetic states remain unclear. Objective This study examines the potential role of FO in suppressing LPS-induced neuroinflammation and cognitive impairment in diabetic animals (DA). Materials and methods Thirty male Wistar rats were divided into 5 groups: i) DA received LPS induction (DA-LPS); ii) DA received LPS induction and 1 g/kg FO (DA-LPS-1FO); iii) DA received LPS induction and 3 g/kg FO (DA-LPS-3FO); iv) animals received normal saline and 3 g/kg FO (NS-3FO) and v) control animals received normal saline (CTRL). Y-maze test was used to measure cognitive performance, while brain samples were collected for inflammatory markers and morphological analysis. Results DA received LPS induction, and 1 or 3 g/kg FO significantly inhibited hyperglycaemia and brain inflammation, as evidenced by lowered levels of pro-inflammatory mediators. Additionally, both DA-LPS-1FO and DA-LPS-3FO groups exhibited a notable reduction in neuronal damage and glial cell migration compared to the other groups. These results were correlated with the increasing number of entries and time spent in the novel arm of the Y-maze test. Discussion and conclusion This study indicates that supplementation of menhaden FO inhibits the LPS signaling pathway and protects against neuroinflammation, consequently maintaining cognitive performance in diabetic animals. Thus, the current study suggested that fish oil may be effective as a supporting therapy option for diabetes to avoid diabetes-cognitive impairment.

Periodic colonization of Trichogramma japonicum for bio-control of yellow stem borer (Scirpophaga incertulas) in summer low-land rice (Oryza sativa)

Yellow stem borer [Scirpophaga incertulas (Walker)], is a major pest of low-land rice (Oryza sativa L.), causing 30–40% yield losses. The use of biological control agents to suppress yellow stem borer (YSB) population and damage across Asia includes inundative releases of the egg parasitoid, Trichogramma japonicum Ashmead. However, information on the time and number of parasitoids’ releases are lacking to control YSB in summer low-land rice. Therefore, an experiment was conducted during summer seasons of 2018 and 2019 at ICAR-National Institute of Biotic Stress Management, Raipur, Chhattisgarh to standardize the time and number of T. japonicum releases for effective biocontrol of YSB. Experiment consisted of 3 different treatment schedules, viz. T1, Four releases of T. japonicum at weekly intervals on the 7th, 14th, 21st, 28th days after planting (DAT); T2, Four releases of T. japonicum at weekly intervals on the 14th, 21st, 28th, 35th DAT; T3, Four releases of T. japonicum at weekly intervals on the 21st, 28th, 35th, 42nd DAT; and T4, Control (no release of wasps). Significant reduction of YSB-induced damage symptoms was observed in the treatment schedule (T2) consisting of four releases of T. japonicum (@50,000 wasps/ha/release) at weekly intervals on the 14th, 21st, 28th, 35th DAT of rice which significantly reduced the dead heart (9.1%, 45.83% reduction over control) and the white ear (1.8%, 47.05% reduction over control), as compared to untreated control plots (T4) (16.8% dead heart, 3.4% white ear) in summer 2018. Similarly, in summer 2019, the reduction in dead heart and white ear by the treatment (T2) was 43.35% and 46.15% over control, respectively. The significant reduction of YSB-induced damages corresponded with the increased grain yield in (T2) from 2018–19 i.e. 12.74–20.18% across the seasons. The results suggest that the (T2) augmentative releases provided ecologically viable bio-control of YSB during the summer seasons in low-land rice.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association's efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.

The effects of probiotic-based additives on aflatoxin intoxication in Piaractus mesopotamicus: a study of liver histology and metabolic performance.

Mycotoxins, produced by fungi, can contaminate fish food and harm their health. Probiotics enhance immune balance and primarily function in the animal intestine. This study aimed to assess aflatoxin's impact on Piaractus mesopotamicus and explore probiotic-based additive (PBA) benefits in mitigating these effects, focusing on antioxidant activity, biochemical indices, and hepatic histopathology. Two experiments were conducted using P. mesopotamicus fry. The first experimental assay tested various levels of aflatoxin B1 (0.0, 25.0, 50.0, 100.0, 200.0, and 400.0µg kg-1) over a 10-day period. The second experimental assay examined the efficacy of the probiotic (supplemented at 0.20%) in diets with different levels of aflatoxin B1 (0.0, 25.0, and 400.0µg kg-1) for 15 days. At the end of each assay, the fish underwent a 24-hour fasting period, and the survival rate was recorded. Six liver specimens from each treatment group were randomly selected for metabolic indicator assays, including superoxide dismutase, catalase, alanine aminotransferase, aspartate aminotransferase, and albumin. Additionally, histopathological analysis was performed on six specimens. The initial study discovered that inclusion rates above 25.0µg kg-1 resulted in decreased activity of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALB (albumin), CAT (catalase), and SOD (superoxide dismutase), accompanied by liver histopathological lesions. In the second study, the inclusion of PBA in diets contaminated with AFB1 improved the activity of AST and ALT up to 25.0µg kg-1 of AFB1, with no histopathological lesions observed. The study demonstrated the hepatoprotective effects of PBA in diets contaminated with AFB1. The enzyme activity and hepatic histopathology were maintained, indicating a reduction in damage caused by high concentrations of AFB1 (400.0µg kg-1 of AFB1). The adverse effects of AFB1 on biochemical and histopathological parameters were observed from 25.0µg kg-1 onwards. Notably, PBA supplementation enhanced enzymatic activity at a concentration of 25µg kg-1 of AFB1 and mitigated the effects at 400.0µg kg-1 of AFB1. The use of PBAs in pacu diets is highly recommended as they effectively neutralize the toxic effects of AFB1 when added to diets containing 25.0µg kg-1 AFB1. Dietary inclusion of aflatoxin B1 at a concentration of 25.0µg kg-1 adversely affects the liver of Piaractus mesopotamicus (Pacu). However, the addition of a probiotic-based additive (PBA) to the diets containing this concentration of aflatoxin neutralized its toxic effects. Therefore, the study recommends the use of PBAs in Pacu diets to mitigate the adverse effects of aflatoxin contamination.

A Sand Boil Database for Piping Risk Management in the Po River, Italy

Sand boil formation at the toe of river embankments is the typical manifestation of the initiation and progression of an internal erosion process known as backward erosion piping, which is recognized to be a major concern in many river systems worldwide. In Italy, more than 130 sand boils have been detected along the Po River, many of them experiencing recurrent reactivations during high-water events. In recent years, as part of the activities of the European project LIFE SandBoil, the Italian authority responsible for flood protection and flood damage reduction along the Po River has implemented a GIS-based web application to catalogue the sand boils observed in its operating area. The resulting database allows keeping records of a comprehensive and varied set of information, in terms of predisposing factors, initiation conditions and surface effects. Taking as a reference a well-documented cross-section of the Po River prone to piping, this paper describes the main features of this versatile and flexible tool, whose long-term aim is to support vulnerability studies and the development of risk maps against piping. The database, which might also accommodate data from different river basins, is thus meant to help in flood risk management, by suggesting priorities for the implementation of mitigation measures and allowing the monitoring of intervention effectiveness.

The role of pantothenic acid in alleviating hypoxia-induced liver injury of sub-adult grass carp (Ctenopharyngodon idellus): Possible mechanisms and implication

In aquaculture, hypoxia poses a significant threat to fish growth and survival. Despite this, there is limited research on the impact of pantothenic acid (PA) in enhancing the anti-hypoxia stress capability of fish. The primary objective of this study was to explore the effects and potential mechanisms of PA in alleviating hypoxia-induced liver injury in sub-adult grass carp. To achieve this, six experimental diets containing varying levels of PA (0.08, 11.95, 24.95, 37.95, 50.95, and 63.95 mg/kg) were formulated and administered to grass carp (initial weight 696.22 ± 2.45 g) for 63 days. Following the dietary intervention, the fish were segregated into hypoxia and control groups and treated for 96 h. The findings revealed that optimal PA levels could enhance the growth performance of sub-adult grass carp and ameliorate the adverse impacts of hypoxia. First, optimal PA levels reduced serum levels of glutamate-oxaloacetate transaminase (GOT), glutamate-pyruvate transaminase (GPT), and lactate dehydrogenase (LDH), as well as mitigated hepatocyte vacuolization, improved liver and mitochondrial morphology, thereby alleviating hypoxia-induced liver injury. Furthermore, optimal PA levels were associated with increased contents of serum cortisol, glucose, liver glycogen, pyruvate, and the activities of Pantothenate kinase 2 (PanK2) and coenzyme A (CoA), while liver lactate content and LDH activity were reduced, indicating improvements in energy metabolism and PA utilization, potentially mediated by the down-regulation of hypoxia-inducible factor-1α (HIF-1α) mRNA level. Moreover, optimal PA levels decreased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, enhanced liver antioxidant capacity, down-regulated autophagy-related gene mRNA levels, and up-regulated autophagy receptor protein 62 (p62) protein level, suggesting a reduction in oxidative damage and autophagy. Finally, a rise in levels of mitochondrial quality control-related mRNAs such as mitofusin 1/2 (MFN1/2), dynamin-related protein-1 (DRP-1), and nuclear respiratory factor 1/2 (Nrf-1/2) was observed, together with increment in the protein levels of PTEN induced putative kinase 1 (PINK1), BCL-2 interacting protein 3 (BNIP3) and FUN14 domain-containing protein 1 (FUNDC1). These alterations hinted at the role of PA in preserving mitochondrial homeostasis. In conclusion, PA exhibited a protective role against hypoxia-induced liver injury by enhancing liver energy metabolism, bolstering antioxidant defenses, suppressing autophagy, and maintaining mitochondrial homeostasis. Through an assessment of percentage weight gain (PWG) and liver ROS level, the requirements of PA for promoting growth and resilience to hypoxia-induced liver injury in sub-adult grass carp were determined to be 37.44 mg/kg and 42.57 mg/kg, respectively.

Preclinical and Clinical Studies on the Use of Extracellular Vesicles Derived from Mesenchymal Stem Cells in the Treatment of Chronic Wounds.

To date, the widespread implementation of therapeutic strategies for the treatment of chronic wounds, including debridement, infection control, and the use of grafts and various dressings, has been time-consuming and accompanied by many challenges, with definite success not yet achieved. Extensive studies on mesenchymal stem cells (MSCs) have led to suggestions for their use in treating various diseases. Given the existing barriers to utilizing such cells and numerous pieces of evidence indicating the crucial role of the paracrine signaling system in treatments involving MSCs, extracellular vesicles (EVs) derived from these cells have garnered significant attention in treating chronic wounds in recent years. This review begins with a general overview of current methods for chronic wound treatment, followed by an exploration of EV structure, biogenesis, extraction methods, and characterization. Subsequently, utilizing databases such as Google Scholar, PubMed, and ScienceDirect, we have explored the latest findings regarding the role of EVs in the healing of chronic wounds, particularly diabetic and burn wounds. In this context, the role and mode of action of these nanoparticles in healing chronic wounds through mechanisms such as oxygen level elevation, oxidative stress damage reduction, angiogenesis promotion, macrophage polarization assistance, etc., as well as the use of EVs as carriers for engineered nucleic acids, have been investigated. The upcoming challenges in translating EV-based treatments for healing chronic wounds, along with possible approaches to address these challenges, are discussed. Additionally, clinical trial studies in this field are also covered.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study

BackgroundThis study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data.MethodsThe Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes.ResultsAmong 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23–82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53–0.86], p = 0.001) and methotrexate (OR 0.68 [0.47–0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64–0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual.ConclusionsThis study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Construction of dental pulp decellularized matrix by cyclic lavation combined with mechanical stirring and its proteomic analysis

The decellularized matrix has a great potential for tissue remodeling and regeneration; however, decellularization could induce host immune rejection due to incomplete cell removal or detergent residues, thereby posing significant challenges for its clinical application. Therefore, the selection of an appropriate detergent concentration, further optimization of tissue decellularization technique, increased of biosafety in decellularized tissues, and reduction of tissue damage during the decellularization procedures are pivotal issues that need to be investigated. In this study, we tested several conditions and determined that 0.1% Sodium dodecyl sulfate and three decellularization cycles were the optimal conditions for decellularization of pulp tissue. Decellularization efficiency was calculated and the preparation protocol for dental pulp decellularization matrix (DPDM) was further optimized. To characterize the optimized DPDM, the microstructure, odontogenesis-related protein and fiber content were evaluated. Our results showed that the properties of optimized DPDM were superior to those of the non-optimized matrix. We also performed the 4D-Label-free quantitative proteomic analysis of DPDM and demonstrated the preservation of proteins from the natural pulp. This study provides a optimized protocol for the potential application of DPDM in pulp regeneration.

Essential Oil of Psidium glaziovianum Kiaersk Alleviates the Effects of Complete Freund’s Adjuvant (CFA)-Induced Arthritis by Regulating Inflammation and Oxidative Stress

Rheumatoid arthritis (RA) is a chronic and debilitating condition that affects a significant number of individuals worldwide. Unfortunately, the currently available therapeutic approaches often yield unsatisfactory results and may be accompanied by harmful side effects. A medicinal plant called Psidium glaziovianum Kiaersk has potential benefits in the treatment of this condition due to its anti-inflammatory and analgesic properties. In this study, our objective was to investigate the potential therapeutic effects of P. glaziovianum essential oil (PgEO) in alleviating arthritis symptoms in mice induced by Complete Freund’s Adjuvant (CFA). The effect of P. glaziovianum essential oil was evaluated in mice with Complete Freund’s Adjuvant (CFA)-induced arthritis. Edema sizes, macroscopic and radiographic images, cytokine levels, and oxidative stress were evaluated. Administration of PgEO at dosages of 50 and 100 mg/kg effectively prevented CFA-induced osteoarticular changes in arthritic mice, resulting in a significant reduction in joint damage. Additionally, the PgEO treatment exhibited the ability to minimize edema, a common symptom associated with arthritis. Furthermore, PgEO can modulate the levels of pro-inflammatory cytokines and oxidative stress, both of which play crucial roles in the progression of the disease. In conclusion, our study suggests that PgEO holds great potential as a natural therapeutic agent for rheumatoid arthritis.

Dynamic behavior of axially loaded masonry walls strengthened with different innovative techniques under explosion loading

In the realm of construction engineering, brick masonry stands out as a pivotal structural element, renowned for its widespread application. Given the load-bearing nature of masonry structures, the ramifications of wall failure under extreme loads induced by explosions are profound. Particularly concerning is the out-of-plane failure of walls, which occurs without warning and affords scant time for assessment of their response. Brick masonry, characterized by its brittleness and susceptibility to cracking, presents inherent challenges in this regard. Recent examples, such as the Beirut explosion in 2020 and the Nashville bombing in 2020, vividly illustrate the devastating consequences of inadequate blast resistance in masonry structures. These incidents serve as poignant reminders of the imperative to fortify masonry constructions against explosive threats. While ample research exists on the behavior of free-standing braced and unbraced masonry walls subjected to explosive loading, there remains a notable gap in understanding the response of strengthened masonry walls exposed to blast loading, especially when carrying varying axial loads. This study addresses this gap by investigating different strengthening methodologies, namely (1) Cement-mortar plaster, (2) Ferro-cement, and (3) Carbon Fiber-Reinforced Polymer (CFRP) laminate, aimed at enhancing the anti-blast performance of unreinforced masonry walls. The experimentation focuses on a specific unreinforced masonry wall measuring 5000 × 2800 × 230 mm3, constructed from clay bricks and subjected to axial compressive loads of 51, 30, and 9kN/m, corresponding to the loads on the 1st, 2nd, and 3rd storey walls of a 3-storey masonry building, respectively. Utilizing a sophisticated finite-elements code, Abaqus, equipped with an explicit module and Concrete Damage Plasticity model, the blast simulations are meticulously conducted. The walls are meticulously modeled through detailed micro-modeling techniques. Results showed that the utilization of CFRP on the explosion-facing surface of the wall resulted in a remarkable reduction in damage, with the highest decrease of 64% achieved under the lowest axial compression. Conversely, the minimum decrease of 61.71% was recorded under maximum axial compression, highlighting the efficacy of CFRP in mitigating damage caused by explosions on walls. This research sheds light on effective methods to enhance the blast resistance of masonry walls, offering valuable insights for improving structural resilience and informing building codes. Its findings are crucial for ensuring the safety and security of infrastructure against explosive threats, ultimately safeguarding lives and property.

Review on millets dehulling and pearling technologies and machinery

AbstractThis paper presents a comprehensive analysis of recent advancements in the mechanization of millet processing technologies. In the last decade, many researchers have worked on millet postharvest processing technologies and developed many machines; however, there is a lack of collective information. The design, development, and performance aspects of millet threshing, dehulling/pearling, and cleaning are comprehensively reviewed and discussed in this review. Various studies are examined, which explore these machines' operational parameters and performance. The findings highlight the significant improvements in threshing and pearling efficiency, grain damage reduction, and ergonomic benefits in comparison to traditional manual methods. This comprehensive review of millet machinery helps to identify the research gap and establish a platform for optimum design and development for the future. Additionally, this helps to improve the level of mechanization in millet processing. The paper contributes valuable insights into improving postharvest processing methods for various millet varieties, thus aiding in promoting the utilization and commercialization of these nutritious and sustainable crops.Practical applicationsUnderstanding of engineering properties of millets for further development and improvement of available millet dehulling machinery. The knowledge of factors involved in millet dehulling and pearling helps in testing and evaluation of millet processing machinery. The comprehensive information about the millet machinery improve mechanization of the millet‐based industries.

A synthetic resveratrol-curcumin hybrid derivative exhibits chemopreventive effects on colon pre-neoplastic lesions by targeting Wnt/β-catenin signaling, anti-inflammatory and antioxidant pathways.

The present study aimed to evaluate the chemopreventive effects of the hybrid against pre-neoplastic lesions induced in the colon of rodents. The doses were determined based on the reduction in DNA damage induced by doxorubicin [15 mg/kg body weight (b.w.)] in peripheral blood of Swiss mice. Doses of 8, 16, 32, and 64 mg/kg b.w. were antimutagenic. For the evaluation of pre-neoplastic lesions in the colon, Wistar rats were treated with PQM-162 at doses of 0.5, 1, and 2 mg/kg b.w. for 6 weeks using three approaches: simultaneous treatment, pre-treatment, and post-treatment. Pre-neoplastic lesions were induced with 1,2 dimethylhydrazine (160 mg/kg b.w.). PQM-162 reduced the formation of aberrant crypt foci in the simultaneous treatment and post-treatment. TNF-α and COX-2 mRNA levels decreased, while Nrf2 mRNA levels increased. PQM-162 also reduced the expression of COX-2, PCNA, and β-catenin protein markers and increased Nrf2 expression. Our findings suggest a chemopreventive potential of PQM-162 in colorectal carcinogenesis, which acts on anti-inflammatory, antioxidant, and cell proliferation pathways.

MitoQ Treatment Mitigates Senescence Burden in DOXO-Induced Senescent Endothelial Cells Through Reductions in mtROS and DNA Damage

Cardiovascular toxicity is one of the adverse consequences of chemotherapy that limits treatment. Specifically, chemotherapeutics such as doxorubicin (DOXO) can lead to endothelial dysfunction through the induction of reactive oxygen species (ROS) and mitochondrial ROS (mtROS) production. MtROS are chemically reactive molecules generated as byproducts of oxidative phosphorylation during mitochondrial respiration. DOXO exacerbates its cardiotoxic effects by amplifying mtROS production, leading to an increase in DNA damage and cell senescence, particularly in endothelial cells (ECs). MitoQ is a mitochondria-targeted antioxidant designed to accumulate within the mitochondria and mitigate oxidative damage by neutralizing mtROS. However, whether MitoQ can rescue mtROS-induced DNA damage and senescence remains elusive. Here, we tested the hypothesis that MitoQ will attenuate DOXO-induced mtROS thus blunting DNA damage and subsequent EC senescence. Human umbilical vein endothelial cells (HUVECs) were simultaneously subjected to 24-hour treatments with DOXO (250nM) and MitoQ (250nM). To evaluate the antioxidative effect of the MitoQ, we examined mitochondrial superoxide using MitoSOX. The results demonstrated that DOXO increases mitochondrial superoxide by 40% (Fig1, p=0.019), whereas addition of MitoQ (MitoQ+DOXO) attenuated mitochondrial superoxide significantly compared to the DOXO group (Fig1, p=0.033). Gene expression of senescence markers, p16 and p21, and Senescence Associated Secretory Phenotypes (SASPs) factors were also examined to assess the effect of MitoQ on senescent endothelial cells. p16 was significantly reduced in the MitoQ+DOXO treatment group compared to the DOXO alone (Fig2, p=0.0090). MitoQ+DOXO lowered p21 expression by 35%, although this difference did not reach significance (Fig2, p=0.340). Moreover, MitoQ+DOXO reduced the SASP factors, IL-8, IL-6 and MCP-1, by more than 54% in comparison to the DOXO group (Fig2, all p≤0.027). Senescent endothelial cells were examined for 53BP1, a double-stranded DNA break marker, using an immunofluorescence (IF) assay. MitoQ+DOXO reduced 53BP1 by 32.6% compared to the DOXO-treated group (Fig3, p=0.011). We also assessed cell proliferation using Bromodeoxyuridine (BrdU) assay. In line with other results, the BrdU assay indicates that the proliferative capability of MitoQ+DOXO-treated cells was improved by more than 20% compared to DOXO-induced senescent cells (Fig4, p=0.008). Our findings suggest that MitoQ can mitigate DOXO-induced mtROS, attenuate DNA damage, and ameliorate senescence in endothelial cells. This provides mechanistic insight suggesting that mtROS may be a driver of cellular senescence in ECs via an increase in DNA damage and MitoQ may be an effcacious therapeutic to treat chemotherapy-induced cardiovascular toxicity. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG048366, T32 HL139451, F31 AG076312, R01 AG077751, R01 AG076748, Nora Eccles Treadwell foundation (NETF), and Veteran's Affairs Merit Review Award I01 BX004492. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

ASCORBIC ACID SUPPLEMENTATION FOR ADJUNCTIVE TREATMENT OF PULMONARY TUBERCULOSIS: REVIEW OF LABORATORY RESEARCH AND CLINICAL TRIALS IN INDONESIA

Background: Tuberculosis (TB) is a highly lethal global disease caused by Mycobacterium tuberculosis (Mtb), which has affected approximately a quarter of the world's population. Ascorbic acid is acknowledged for its strong antioxidant properties, its ability to modulate the immune system, and its effectiveness against Mtb infections. Method: Literature search based on specific keywords following the PICO (Patient, Intervention, Comparison, Outcome) research question was carried out on Pubmed, Scopus and Google Scholar databases, as well as Garuda for clinical research in Indonesia. The flow of the literature search followed PRISMA and risk of bias analysis using the Rob2 tool. Discussion: Laboratory studies have shown that ascorbic acid, whether given by itself or in conjunction with standard anti-TB medications, can decrease the quantity of Mtb colony-forming units (CFU). Similar outcomes were witnessed in experiments conducted with mice. The administration of ascorbic acid to mice infected with Mtb also led to a reduction in lung tissue damage. Clinical trials carried out in Indonesia demonstrated that the addition of ascorbic acid resulted in a greater sputum conversion rate in comparison to patients who did not receive this supplementation. Conclusion: Ascorbic acid exhibits several clinical attributes that prove beneficial in the management of TB.

Impact of Local Governments’ Disaster Preparedness Capability and Local Characteristics on Storm and Flood Damage Reduction: Focusing on Disaster Management Resource

This study empirically analyzes the impact of local governments' disaster preparedness capabilities and local characteristics on storm and flood damage. It considers the budget allocated by local governments for securing and managing disaster management resources as a disaster preparedness capability. Impervious area is used as a local characteristic. Disaster management resources are significant because they are built and utilized during preparedness, response, and recovery phases. Local characteristics should also be considered because of their influence on the impact of disasters. The results of this study indicate that the ratio of the disaster management resource budget affects the reduction of damage. The impact of the budget increases in areas with a relatively higher percentage of impervious area. Therefore, local governments must secure and manage disaster management resources as part of their disaster preparedness. This can be achieved by utilizing ordinances and plans.

제주도 폭염 직접 피해 원인의 사회적 부검

Due to consistent temperature rise, damages from heatwaves are steadily increasing as time passes. Consequently, national attention towards heatwaves has heightened, leading to a significant rise in preliminary research aimed at analyzing this phenomenon. However, previous research on heatwaves has been limited to topics within climatology, impact variables, risk assessment, and related subjects in meteorology and vulnerability. In this study, the concept and methodology of social autopsy were introduced to analyze the causes of heatwave damage from a sociological perspective through social and environmental analysis. Firstly, the heatwave damage indicator selected for analysis was the number of heat-related illness cases, and the region chosen for the application of social autopsy was Jeju Island, where heat-related illnesses are most pronounced in the country. For the selected area, a control group was identified by contrasting areas with similar environmental conditions but significant differences in the prevalence of heat-related illnesses. Social and environmental factors were then analyzed based on personal social relationships, socioecological structures, and geographical characteristics to analyze heat-related illnesses in different regions. In a quantitative study analyzing the socio-ecological structure using social capital assessments, the results showed that in areas with a high incidence of heat-related illnesses (Hwabuk-dong, Gujo-eup), the probability of experiencing heat-related illnesses increased by 3.2 times when personal organizational trust and residential relationships increased. In contrast, the probabilities decreased by 91.5% and 95.1%, respectively, with an increase in mobile communication and participation in elections. Next, for the analysis of individual temperament and living environment, qualitative research through in-depth interviews was conducted with direct victims who sought medical attention for heat-related illnesses. The results revealed that all subjects exhibited high responsibility, diligence, and proactiveness, with a low level of awareness of the risk of heat-related illnesses. Additionally, growing up in environments with economic difficulties during childhood and youth was associated with a sense of responsibility and diligence, demonstrating a connection to the burden of taking responsibility for family and home, and continuing to work without stopping despite exposure to risks (heat-related illnesses). Finally, an analysis of the geographical characteristics of the region revealed that areas with a higher incidence of anti-Japanese movements and victims of the April 3rd incident had a higher prevalence of heat-related illnesses. This confirmed that the environmental characteristics of Jeju Island were responsible for the majority of heat-related illnesses in the Gujo-eup and Jocheon-eup areas. Based on these findings, it was concluded that the occurrence of direct heatwave victims, namely heat-related illness patients, is influenced not only by meteorological factors but also by a complex interplay of social, environmental, and individual temperament factors. Consequently, it is suggested that instead of a uniform approach to heatwave damage reduction implemented by the government, region-specific and systematic mitigation measures tailored to each locality are necessary.