Mild Damage Research Articles

Assessment of Land Damage Status Using Frequency Method on Several Land Use for Biomass Production in Payakumbuh City

Intensive use of land for agricultural businesses causes the land to become very dynamic and causes a decrease in soil quality for producing biomass. This research aims to determine environmental conditions (level of damage to land and soil for biomass production) and the factors that cause soil damage in Payahkumbuh City. Land surveys were carried out using the research method in five sub-districts. Samples taken in the field are disturbed soil samples for analysis of physical properties (texture, BV, TRP, and permeability). In contrast, disturbed soil samples are used to analyze chemical soil properties (c.organic, pH, DLH, Redok). Apart from that, he also observed environmental conditions such as rocks on the surface and the depth of the soil. Next, the soil samples are explained in the soil laboratory of the Department of Soil Science and Land Resources. Data from soil physical and chemical property variables are processed, averaged, and compared with soil health standards following PP No. 150 of 2000. The research results show that the results of land identification and verification show that the land in the five sub-districts of Payakumbuh City in the research area has a Light Damage Status (RI) covering an area of 2391.65 ha and Moderate Damage (RII) covering an area of 1856.76 ha. From 10 observation points, the land in the research area has two levels of soil damage: moderate and light. Soil damage is caused by limiting factors. In moderate damage status, the limiting factors are (RII-vpre), namely soil porosity, degree of air escape, redox reactions, and electrical conductivity. Meanwhile, the limiting factors in soil with mild damage are (RI-vre) soil porosity, redox reactions, and electrical conductivity.

Preclinical delayed toxicity studies of BCMA CAR T-cell injection in B-NDG mice with multiple myeloma.

Based on the efficacy data from the previous study of B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell injection, we further examined the delayed toxicity for 8 weeks after a single dose of BCMA CAR T-cell injection to observe possible toxic reactions. B-NDG mice transplanted with multiple myeloma (MM) cells were given a single dose of BCMA CAR T-cell injection at two dosages or human normal T cells and then subjected to examinations including clinical signs, weight and food intake measurements, haematology, blood biochemical analysis, cytokine assay, T-lymphocyte subpopulation quantification and histopathology on days 28 and 56 after dosing. In addition, quantitative polymerase chain reaction (qPCR) was used to quantify DNA fragments in different tissues to assess the tissue distribution of CAR and provide a basis for its preclinical safety evaluation and clinical dosing. In the delayed toxicity study, no mortality or significant toxic effects such as reductions in food intake, body weight, relevant biochemical parameters and target organ weights were observed in the BCMA CAR T-cell-treated groups. Compared to the model group, restorative changes in clinical signs and clinicopathology indicating therapeutic effects were seen in the BCMA CAR T-cell-treated groups. Human-derived cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-12, IL-10, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) could be detected in all cancer cell-bearing mice by cytokine level measurement. IFN-γ levels showed a geometric increase due to the graft versus host disease (GVHD) response induced in the mice, while the levels of the other cytokines did not show significant changes. Histopathological examination indicated that the BCMA CAR T-cell treatment groups showed mixed cellular infiltration of human-derived T cells, cancer cells, and inflammatory cells in several target organs including the liver, spleen, lung, and kidney, and some of them showed mild tissue damage, but the number of the animals and the severity of damage were significantly less than those of the T-cell control group as well as the model group. The results of the tissue distribution study showed that BCMA CAR T cells were mainly concentrated in the kidney, lung, bone marrow and the related immune organs/tissues, and the distribution of BCMA CAR T cells was highly consistent with that of MM cells, suggesting that BCMA CAR T cells could follow the cancer cells during metastatic targeting of the tissues. The present study demonstrated a low toxicity of BCMA CAR T-cell injection, with manageable side effects and good anticancer activity and without observable adverse effects. This study provides data to support future clinical studies of BCMA CAR T-cell injection for MM.

Exploring the potential of native sea urchins as ex situ coral propagation allies

Caribbean coral reefs face unprecedented decline due to anthropogenic and environmental stressors, necessitating active restoration efforts. Among the strategies to conserve and restore reef ecosystems, land‐based sexual propagation of corals is crucial for preserving genetic diversity and population resilience. This study explores the efficacy of utilizing native sea urchin herbivory to control benthic macroalgal proliferation and enhance coral growth in land‐based propagation systems. Three captive‐reared urchin species—Lytechinus variegatus, Tripneustes ventricosus, and Diadema antillarum—were evaluated for their influence on algal cover and growth of sexually propagated brain coral Pseudodiploria strigosa. Juveniles of each urchin species were co‐cultured with 6‐month‐old coral colonies over a 105‐day experiment. Results indicated that all urchin treatments effectively reduced algal cover compared to controls; however, only T. ventricosus significantly increased coral growth rate, while the other urchin species did not have a notable effect. Despite differences in growth, coral survival was consistently high across all treatments. Benthic community analysis revealed shifts in algal composition, with D. antillarum grazing associated with increased crustose coralline algae. However, overgrazing by D. antillarum may have resulted in mild peripheral tissue damage to some corals. Urchin survival remained high, suggesting potential for downstream utilization in restoration (e.g. urchin population enhancement). This study highlights the potential of native urchins as biocontrol agents in coral propagation, emphasizing the importance of species‐specific interactions in shaping benthic communities and promoting coral resilience.

Phenotypes of patients with lupus-associated pulmonary hypertension in the Chinese Han population: a cluster analysis.

Pulmonary hypertension (PH) is a severe complication of systemic lupus erythematosus (SLE). This study investigated the clinical features of patients with SLE-PH in China based on disease manifestations and organ involvement to define precise treatment of SLE and early prevention of complications. In total, 205 SLE-PH patients were included in this study. A cluster analysis was applied according to six clinical and serological variables to define different subgroups of patients. The survival rates of SLE-PH patients and risk factors that influenced prognosis were also compared and a clinical prediction model was developed for the diagnosis of associated lupus nephritis (LN). Patients were clustered in five groups. Patients in cluster 1 had severe renal damage (all patients had LN and had the highest creatinine and urea nitrogen and the lowest eGFR levels). Patients in cluster 2 had mild renal damage (more than half of the patients had associated LN and 87.5% had increased urinary protein levels but presented a lower degree of renal damage than those in the first group. Patients in cluster 3 had low-grade proteinuria (all patients had 24h urinary protein < 0.5g). Patients in cluster 4 had hematuria or urinary tubular damage (26% of patients had associated LN, but none of the patients had proteinuria. In cluster 5, patients barely had any major organ involvement. The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies > 364.64IU/mL and neutrophil-to-leukocyte ratio (NLR) > 5.55. Our findings provide evidence indicating that SLE-PH presents varying clinical phenotypes and the treatment varies accordingly, suggesting the need for individualized treatment. Key Points • Clustered grouping of patients with SLE-PH is associated with renal injury. • This may be because PH and LN share a common pathogenesis. • The clinical prediction model for a diagnosis of SLE-PH-LN was anti-dsDNA antibodies >364.64 IU/mL and NLR >5.55.

Increased DNA damage in full-grown oocytes is correlated with diminished autophagy activation

Unlike mild DNA damage exposure, DNA damage repair (DDR) is reported to be ineffective in full-grown mammalian oocytes exposed to moderate or severe DNA damage. The underlying mechanisms of this weakened DDR are unknown. Here, we show that moderate DNA damage in full-grown oocytes leads to aneuploidy. Our data reveal that DNA-damaged oocytes have an altered, closed, chromatin state, and suggest that the failure to repair damaged DNA could be due to the inability of DDR proteins to access damaged loci. Our data also demonstrate that, unlike somatic cells, mouse and porcine oocytes fail to activate autophagy in response to DNA double-strand break-inducing treatment, which we suggest may be the cause of the altered chromatin conformation and inefficient DDR. Importantly, autophagy activity is further reduced in maternally aged oocytes (which harbor severe DNA damage), and its induction is correlated with reduced DNA damage in maternally aged oocytes. Our findings provide evidence that reduced autophagy activation contributes to weakened DDR in oocytes, especially in those from aged females, offering new possibilities to improve assisted reproductive therapy in women with compromised oocyte quality.

Pre-and post-emergence herbicide selectivity in peanuts at an early stage

Studies on herbicide selectivity to peanuts detected differences according to the evaluated active ingredient and genotypes. This study analyzed the herbicide selectivity of two genotypes at an early stage. Pre-emergence (trifluralin, pendimethalin, diclosulam, s-metolachlor, imazethapyr + flumioxazin, clomazone, sulfentrazone, and imazapic) and post-emergence (imazapic, bentazon, bentazon + imazamox, clethodim, quizalofop-p-ethyl, cloransulam-methyl, s-metolachlor, lactofen, 2,4-D, and carfentrazone) applications were assessed in 1253 OL and 2133 OL breeding lines. The effects of pre- (PRE) and post-emergence (POST) herbicides were the same for both genotypes, with PRE not affecting seedling emergence and shoot and root dry mass. Diclosulam was among the most selective PRE herbicides, while the clomazone treatment caused only mild damage. All tested POST herbicides caused damage for up to 14 days after application (DAA). At 28 DAA, most herbicides exhibited the same damage as the untreated control. Lactofen caused mild damage (11.8%) without reducing plant height and shoot and root dry mass. Diclosulam, clomazone, and lactofen are unregistered for peanut crops in Brazil, and further studies should test their selectivity for peanut cultivars. Screening studies on selectivity to imazapic, 2,4-D, and carfentrazone are also relevant to identifying sources of tolerance in peanut germplasm.

Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system.

Providencia alcalifaciens is a Gram-negative bacterium found in various water and land environments and organisms, including insects and mammals. Some P. alcalifaciens strains encode gene homologs of virulence factors found in pathogenic Enterobacterales members, such as Salmonella enterica serovar Typhimurium and Shigella flexneri. Whether these genes are pathogenic determinants in P. alcalifaciens is not known. In this study, we investigated P. alcalifaciens-host interactions at the cellular level, focusing on the role of two type III secretion systems (T3SS) belonging to the Inv-Mxi/Spa family. T3SS1b is widespread in Providencia spp. and encoded on the chromosome. A large plasmid that is present in a subset of P. alcalifaciens strains, primarily isolated from diarrheal patients, encodes for T3SS1a. We show that P. alcalifaciens 205/92 is internalized into eukaryotic cells, lyses its internalization vacuole, and proliferates in the cytosol. This triggers caspase-4-dependent inflammasome responses in gut epithelial cells. The requirement for the T3SS1a in entry, vacuole lysis, and cytosolic proliferation is host cell type-specific, playing a more prominent role in intestinal epithelial cells than in macrophages or insect cells. In a bovine ligated intestinal loop model, P. alcalifaciens colonizes the intestinal mucosa and induces mild epithelial damage with negligible fluid accumulation in a T3SS1a- and T3SS1b-independent manner. However, T3SS1b was required for the rapid killing of Drosophila melanogaster. We propose that the acquisition of two T3SS has allowed P. alcalifaciens to diversify its host range, from a highly virulent pathogen of insects to an opportunistic gastrointestinal pathogen of animals.

Heightened Reticulospinal Excitability after Severe Corticospinal Damage in Chronic Stroke.

After severe corticospinal tract damage poststroke in humans, some recovery of strength and movement proximally is evident. It is possible that alternate motor pathways, such as the reticulospinal tract, may be upregulated to compensate for the loss of corticospinal tract input. We investigated the extent of reticulospinal tract excitability modulation and its inter-dependence on the severity of corticospinal tract damage after stroke in humans. We used a novel startle conditioned transcranial magnetic stimulation paradigm to elicit ipsilateral motor evoked potentials, an index of reticulospinal tract excitability, in 22 chronic stroke participants with mild to severe corticospinal tract damage and 14 neurotypical age-matched controls. We found that ipsilateral motor evoked potential presence was higher in the paretic arm of people with severe corticospinal tract damage compared to their non-paretic arm, people with mild corticospinal tract damage, and age-matched controls. Interestingly, ipsilateral motor evoked potential presence was correlated with motor impairment across the entire stroke cohort, whereby individuals with worse impairment exhibited more frequent ipsilateral motor evoked potentials (ie, higher reticulospinal tract excitability). Following severe corticospinal tract damage, upregulated reticulospinal tract activity may compensate for a loss of corticospinal tract input, providing some proximal recovery of isolated and within-synergy movements, but deficits in performing out of synergy movements and finger fractionation remain. Interventions aimed at modulating the reticulospinal tract could be beneficial or detrimental to ameliorating motor impairment depending on the degree of reliance on this pathway for residual motor output. ANN NEUROL 2024.

A Genetically Encoded Sensor for Real-Time Monitoring of Poly-ADP-Ribosylation Dynamics In Vitro and in Cells.

ADP-ribosylation, the transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) groups to proteins, is a conserved post-translational modification (PTM) that occurs most prominently in response to DNA damage. ADP-ribosylation is a dynamic PTM regulated by writers (PARPs), erasers (ADPr hydrolases), and readers (ADPR binders). PARP1 is the primary DNA damage-response writer responsible for adding a polymer of ADPR to proteins (PARylation). Real-time monitoring of PARP1-mediated PARylation, especially in live cells, is critical for understanding the spatial and temporal regulation of this unique PTM. Here, we describe a genetically encoded FRET probe (pARS) for semiquantitative monitoring of PARylation dynamics. pARS feature a PAR-binding WWE domain flanked with turquoise and Venus. With a ratiometric readout and excellent signal-to-noise characteristics, we show that pARS can monitor PARP1-dependent PARylation temporally and spatially in real-time. pARS provided unique insights into PARP1-mediated PARylation kinetics in vitro and high-sensitivity detection of PARylation in live cells, even under mild DNA damage. We also show that pARS can be used to determine the potency of PARP inhibitors in vitro and, for the first time, in live cells in response to DNA damage. The robustness and ease of use of pARS make it an important tool for the PARP field.

Snapshot of Fall Prevention in Patients Referred to a Neurorehabilitation Unit: A Feasibility Study on the Use of an Airbag Device.

Active wearable devices such as protective smart belts have been proposed to reduce hip impact in the event of a fall. This study primarily evaluated the feasibility and acceptance of a specific protective belt among selected patients identified as being at risk of falling who were admitted to an ICS Maugeri Neurorehabilitation Unit from September 2022 to April 2023. According to previous institutional observations, the device was worn between the 6th and 21st days of recovery. Out of 435 admitted patients, 118 were considered eligible, but 101 declined to participate (about 50% refused to wear the belt without first trying it on; the other 50% found it too heavy or difficult to manage). Among the 17 patients who accepted (users), 9 used the belt correctly. The remaining eight patients refused to wear it after 24 h, due to discomfort. Out of 435 patients admitted, we observed at least one fall in 49 patients, of whom 5 were eligible patients; 1 was a user who had quickly refused to use the belt and fell with mild damage. Two non-eligible patients and one eligible non-user patient experienced falls resulting in hip fractures; only in the latter case could the use of the belt have limited the damage to the hip. Difficulties in recruiting patients and low acceptance of the proposed intervention present further challenges.

The influence of a composition based on exometabolites of Saccharomyces boulardii in relation to the pathogenic and persistent properties of fungi of the genus Candida

Clinical manifestations of mycoses vary widely from mild mucosal damage to severe invasive forms. Currently, the pharmaceutical market offers a wide range of antimycotic drugs, including oral and injectable drugs for systemic and external and local use. Varying degrees of effectiveness are due to the chemical structure and pharmacokinetics. A significant problem is the recurrence of mucosal candidiasis. One of the possible solutions to this problem can be considered the use of exometabolites of bacterial or fungal origin, affecting the morphofunctional structures of fungi of the genus Candida spp. The purpose of the study was to obtain cell-free supernatant of Saccharomyces boulardii (S. boulardii) and herbal extracts, which are the basis of a composition with a preventive effect against fungi of the genus Candida. The authors proposed a composition based on the exometabolite of S. boulardii and herbal extracts for the prevention of candidiasis. Propylene glycol served as a control. The effectiveness of the composition was assessed on clinical isolates of C. albicans, C. glabrata and C. krusei isolated from the vaginal biotope at a dilution of 103-106 CFU/mL. At the first stage, we studied the effect of S. boulardii metabolites on the biological properties of fungi. Next, the fungicidal activity of metabolites and extracts was determined by serial dilution against micromycete isolates. At the final stage, the effect of the composition with the most effective extracts was studied. Under the influence of the supernatant of S. boulardii, micromycetes lost the ability to form growth tubes, and a decrease in the catalase activity of Candida spp. was observed both during carriage and disease. Exometabolites significantly reduced the ability to form film in cultures isolated from patients with vaginal candidiasis. The most effective among the extracts were the extracts of St. John’s wort and coriander. The fungicidal properties of the composition were maintained for 12 hours after co-incubation with all isolates of Candida spp. Thus, the composition is effective against both C. albicans and C. non-albicans carriage and disease.

Factors associated with systemic inflammatory response syndrome negativity at the early stage of sepsis among nonsurviving sepsis patients in intensive care unit

AbstractObjectivesThis study aims to investigate the factors associated with systemic inflammatory response syndrome (SIRS) negativity during the early stage of sepsis in deceased septic patients.MethodsAdult septic patients were included from the Medical Information Mart for Intensive Care IV (MIMIC‐IV) database between 2008 and 2019. Patients who did not survive after 28 days were assigned to the SIRS‐negative or SIRS‐positive group according to whether the SIRS score was less than two points within 24 h of intensive care unit admission. Logistic regression and a restricted cubic spline model were used to analyze factors and dose–response relationships.ResultsA total of 53,150 patients were screened in the MIMIC‐IV database, and 2706 sepsis nonsurvivors were ultimately included, 101 of whom were negative for SIRS. There were significant differences in sequential organ failure assessment (SOFA) scores between groups (8.18 ± 3.58 vs. 9.75 ± 4.28, p &lt; 0.001). Logistic regression analysis indicated that lactate (odds ratio [OR] = 0.75 [95% CI = 0.62–0.90], p = 0.002), SOFA score (OR = 0.93 [95% CI = 0.87–1.00], p = 0.046), and age (OR = 1.04 [95% CI = 0.88–1.15], p = 0.012) were independent factors related to SIRS negativity in septic patients. Analysis with a restricted cubic spline model showed that the OR of SIRS negativity continued to increase with age, particularly for those over 80 years old (p for nonlinearity = 0.024). The OR of SIRS negativity was more than 1 when the SOFA score was &lt;4 (p for nonlinearity = 0.149) and when the lactate was &lt;1 (p for nonlinearity = 0.014).ConclusionsFor sepsis patients with poor prognoses, elderly individuals are more likely to be SIRS negative when they have mild organ dysfunction damage or mild tissue hypoperfusion in the early stage of sepsis. This warranted an opportunity to provide early diagnosis for elderly population with negative SIRS score in order to prevent poor outcomes.

Identification of potential biomarkers of cuproptosis in cerebral ischemia.

Cerebral ischemia can cause mild damage to local brain nerves due to hypoxia and even lead to irreversible damage due to neuronal cell death. However, the underlying pathogenesis of this phenomenon remains unclear. This study utilized bioinformatics to explore the role of cuproptosis in cerebral ischemic disease and its associated biomarkers. R software identified the overlap of cerebral ischemia and cuproptosis genes, analyzed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and explored hub genes. Expressions and localizations of hub genes in brain tissue, cells, and immune cells were analyzed, along with predictions of protein structures, miRNAs, and transcription factors. A network was constructed depicting hub gene co-expression with miRNAs and interactions with transcription factors. Ferredoxin 1 (FDX1) expression was determined using qRT-PCR. Ten cuproptosis-related genes in cerebral ischemia were identified, with GO analysis revealing involvement in acetyl-CoA synthesis, metabolism, mitochondrial function, and iron-sulfur cluster binding. KEGG highlighted processes like the tricarboxylic acid cycle, pyruvate metabolism, and glycolysis/gluconeogenesis. Using the Human Protein Atlas, eight hub genes associated with cuproptosis were verified in brain tissues, hippocampus, and AF22 cells. Lipoyl(octanoyl) transferase 1 (LIPT1), was undetected, while others were found in mitochondria or both nucleus and mitochondria. These genes were differentially expressed in immune cells. FDX1, lipoic acid synthetase (LIAS), dihydrolipoamide S-acetyltransferase (DLAT), pyruvate dehydrogenase E1 component subunit alpha 1 (PDHA1), PDHB, and glutaminase (GLS) were predicted to target 111 miRNAs. PDHA1, FDX1, LIPT1, PDHB, LIAS, DLAT, GLS, and dihydrolipoamide dehydrogenase (DLD) were predicted to interact with 11, 10, 10, 9, 8, 7, 5, and 4 transcription factors, respectively. Finally, FDX1 expression was significantly upregulated in the hippocampus of ovariectomized rats with ischemia. This study revealed an association between cerebral ischemic disease and cuproptosis, identifying eight potential target genes. These findings offer new insights into potential biomarkers for the diagnosis, treatment, and prognosis of cerebral ischemia, and provide avenues for the exploration of new medical intervention targets.

Anatomo-functional changes in neural substrates of cognitive memory in developmental amnesia: Insights from automated and manual Magnetic Resonance Imaging examinations.

Despite bilateral hippocampal damage dating to the perinatal or early childhood period and severely impaired episodic memory, patients with developmental amnesia continue to exhibit well-developed semantic memory across the developmental trajectory. Detailed information on the extent and focality of brain damage in these patients is needed to hypothesize about the neural substrate that supports their remarkable capacity for encoding and retrieval of semantic memory. In particular, we need to assess whether the residual hippocampal tissue is involved in this preservation, or whether the surrounding cortical areas reorganize to rescue aspects of these critical cognitive memory processes after early injury. We used voxel-based morphometry (VBM) analysis, automatic (FreeSurfer) and manual segmentation to characterize structural changes in the brain of an exceptionally large cohort of 23 patients with developmental amnesia in comparison with 32 control subjects. Both the VBM and the FreeSurfer analyses revealed severe structural alterations in the hippocampus and thalamus of patients with developmental amnesia. Milder damage was found in the amygdala, caudate, and parahippocampal gyrus. Manual segmentation demonstrated differences in the degree of atrophy of the hippocampal subregions in patients. The level of atrophy in CA-DG subregions and subicular complex was more than 40%, while the atrophy of the uncus was moderate (-24%). Anatomo-functional correlations were observed between the volumes of residual hippocampal subregions in patients and selective aspects of their cognitive performance, viz, intelligence, working memory, and verbal and visuospatial recall. Our findings suggest that in patients with developmental amnesia, cognitive processing is compromised as a function of the extent of atrophy in hippocampal subregions. More severe hippocampal damage may be more likely to promote structural and/or functional reorganization in areas connected to the hippocampus. In this hypothesis, different levels of hippocampal function may be rescued following this variable reorganization. Our findings document not only the extent, but also the limits of circuit reorganization occurring in the young brain after early bilateral hippocampal damage.

Progressive Tooth Wear Against Resin-Based Restorative Composites.

The composition and properties of resin-based composite materials could affect tooth wear and lead to clinical problems. Therefore, the study objective was to characterize human tooth wear behavior against a bulk-fill restorative (BF) compared to a conventional resin composite (RC) and a CAD/CAM resin nano ceramic (RN). Square-shaped specimens of each material were prepared and sub-divided according to the number of testing cycles (n=8): 100,000, 250,000, and 500,000 cycles. An occlusal wear test was performed using a chewing machine with 49 N, 2 Hz, in 37°C distilled water. Human premolar cusps were used as antagonists. Micro-CT and laser scanner were used to scan antagonists and specimens, respectively. Wear volume was assessed using a software and the wear pattern was examined with SEM. Softening in solvent analysis was performed by measuring the materials' Knoop microhardness (KHN) before and after immersion in ethanol. Wear volume data were analyzed with two-way ANOVA and Student-Neuman-Keuls test (α=0.05). For tooth and specimen wear volume, there was statistical significance for material and number of cycles, but not for the interaction between factors. BF resulted in less tooth (p=0.008) and specimen (p=0.030) wear than RN and RC, which were similar (p⟩0.05). Volume loss increased from 100,000 to 500,000 cycles. BF showed the lowest microhardness (KHN1); and %ΔKHN similar to RC, but greater than RN. BF induced less volume loss to the tooth than RC and RN, while presenting greater wear resistance. The tooth wear pattern and damage progression were mild for all materials. Resin composites show favorable wear behavior, leading to low volume loss and mild structural damage of the tooth. Regular bulk-fill resin composite stands out for its efficient restorative technique, low wear susceptibility and reduced capacity to wear down the tooth.

CYP2E1 in 1,4-dioxane metabolism and liver toxicity: insights from CYP2E1 knockout mice study.

1,4-Dioxane (DX), an emerging water contaminant, is classified as a Group 2B liver carcinogen based on animal studies. Understanding of the mechanisms of action of DX liver carcinogenicity is important for the risk assessment and control of this environmental pollution. Previous studies demonstrate that high-dose DX exposure in mice through drinking water for up to 3 months caused liver mild cytotoxicity and oxidative DNA damage, a process correlating with hepatic CYP2E1 induction and elevated oxidative stress. To access the role of CYP2E1 in DX metabolism and liver toxicity, in the current study, male and female Cyp2e1-null mice were exposed to DX in drinking water (5000 ppm) for 1 week or 3 months. DX metabolism, redox and molecular investigations were subsequently performed on male Cyp2e1-null mice for cross-study comparisons to similarly treated male wildtype (WT) and glutathione (GSH)-deficient Gclm-null mice. Our results show that Cyp2e1-null mice of both genders were resistant to DX-induced hepatocellular cytotoxicity. In male Cyp2e1-null mice exposed to DX for 3 months, firstly, DX metabolism to β-hydroxyethoxyacetic acid was reduced to ~ 36% of WT levels; secondly, DX-induced hepatic redox dysregulation (lipid peroxidation, GSH oxidation, and activation of NRF2 antioxidant response) was substantially attenuated; thirdly, liver oxidative DNA damage was at a comparable level to DX-exposed WT mice, accompanied by suppression of DNA damage repair response; lastly, no aberrant proliferative or preneoplastic lesions were noted in DX-exposed livers. Overall, this study reveals, for the first time, that CYP2E1 is the main enzyme for DX metabolism at high dose and a primary contributor to DX-induced liver oxidative stress and associated cytotoxicity. High dose DX-induced genotoxicity may occur via CYP2E1-independent pathway(s), potentially involving impaired DNA damage repair.

Adverse effects of metamizole on heart, lung, liver, kidney, and stomach in rats

BackgroundMetamizole is banned in some countries because of its toxicity, although it is widely used in some European countries. In addition, there is limited information on its safety profile, and it is still debated whether it is toxic to the heart, lungs, liver, kidneys, and stomach.AimsOur study investigated the effects of metamizole on the heart, lung, liver, kidney, and stomach tissues of rats.MethodsEighteen rats were divided into three groups, wassix healthy (HG), 500 mg/kg metamizole (MT-500), and 1000 mg/kg metamizole (MT-1000). Metamizole was administered orally twice daily for 14 days. Meanwhile, the HG group received pure water orally. Biochemical, histopathologic, and macroscopic examinations were performed on blood samples and tissues.ResultsMalondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in the lung and gastric tissues of MT-500 and MT-1000 groups were almost the same as those of the HG (p > 0.05). However, MDA levels in the heart and liver tissues of MT-500 and MT-1000 groups were higher (p < 0.05) compared to the HG, while tGSH levels and SOD, and CAT activities were lower (p < 0.05). MDA levels of MT-500 and MT-1000 groups in the kidney tissue increased the most (p < 0.001), and tGSH levels and SOD and CAT activities decreased the most (p < 0.001) compared to HG. Metamizole did not cause oxidative damage in the lung and gastric tissue. While metamizole did not change troponin levels, it significantly increased alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels compared to HG. Histopathologically, mild damage was detected in heart tissue, moderate damage in liver tissue, and severe damage in renal tissue. However, no histopathologic damage was found in any groups’ lung and gastric tissues.ConclusionMetamizole should be used under strict control in patients with cardiac and liver diseases and it would be more appropriate not to use it in patients with renal disease.

Exploration of Clozapine-Induced Cardiomyopathy and Its Mechanism.

In this study, by pooling the clinical data of patients who died with a history of long-term clozapine use and by examining their hearts, it was found that long-term clozapine use can lead to cardiomyopathy and that its presentation resembles arrhythmogenic cardiomyopathy (ACM), i.e., it exhibits a predominantly right ventricular fatty infiltration with mild left ventricular damage. The transcriptomic data of rat cardiomyocytes after clozapine intervention were analyzed by transcriptomic approach to explore the causes of clozapine cardiomyopathy. The cause of clozapine cardiomyopathy was then explored by a transcriptomic approach, which revealed that its clozapine action on cardiomyocytes enriched cardiomyocyte-related differential genes in biological processes such as muscle development and response to hypoxia, as well as pathways such as fatty acid metabolism and cellular autophagy. Transcriptomic analysis showed that Egr1, Egr2, ler2, Jun, Mapk9, Nr1d2, Atf3, Bhlhe40, Crem, Cry1, Cry2, Dbp were hub genes for clozapine injury to the myocardium, and that these genes may play an important role in the myocardial ACM-like changes caused by clozapine. Combined with the results of pathological examination and transcriptomic analysis, it can be concluded that the long-term action of clozapine on cardiomyocytes leads to cellular autophagy and subsequent structural remodeling of the heart, and in the remodeling affects fatty acid metabolism, which eventually leads to ACM-like changes.

Deep Convolutional Neural Network for Automated Staging of Periodontal Bone Loss Severity on Bite-wing Radiographs: An Eigen-CAM Explainability Mapping Approach.

Periodontal disease is a significant global oral health problem. Radiographic staging is critical in determining periodontitis severity and treatment requirements. This study aims to automatically stage periodontal bone loss using a deep learning approach using bite-wing images. A total of 1752 bite-wing images were used for the study. Radiological examinations were classified into 4 groups. Healthy (normal), no bone loss; stage I (mild destruction), bone loss in the coronal third (< 15%); stage II (moderate destruction), bone loss is in the coronal third and from 15 to 33% (15-33%); stage III-IV (severe destruction), bone loss extending from the middle third to the apical third with furcation destruction (> 33%). All images were converted to 512 × 400 dimensions using bilinear interpolation. The data was divided into 80% training validation and 20% testing. The classification module of the YOLOv8 deep learning model was used for the artificial intelligence-based classification of the images. Based on four class results, it was trained using fivefold cross-validation after transfer learning and fine tuning. After the training, 20% of test data, which the system had never seen, were analyzed using the artificial intelligence weights obtained in each cross-validation. Training and test results were calculated with average accuracy, precision, recall, and F1-score performance metrics. Test images were analyzed with Eigen-CAM explainability heat maps. In the classification of bite-wing images as healthy, mild destruction, moderate destruction, and severe destruction, training performance results were 86.100% accuracy, 84.790% precision, 82.350% recall, and 84.411% F1-score, and test performance results were 83.446% accuracy, 81.742% precision, 80.883% recall, and 81.090% F1-score. The deep learning model gave successful results in staging periodontal bone loss in bite-wing images. Classification scores were relatively high for normal (no bone loss) and severe bone loss in bite-wing images, as they are more clearly visible than mild and moderate damage.

Ortho-Vanillin Ameliorates Spinetoram-Induced Oxidative Stress in the Silkworm Bombyx mori: Biochemical and In Silico Insights.

This study investigates the toxic effects of the insecticide spinetoram on the model organism Bombyx mori (Linnaeus) and explores the potential ameliorative properties of O-Vanillin. Sub-lethal concentrations of spinetoram were given to silkworm larvae via oral feed, resulting in reduced body weight, larval length, and impaired cocoon characteristics. A study of the enzymatic and non-enzymatic antioxidants revealed oxidative stress in the gut, fat body, and silk gland tissues, characterized by decreased antioxidants and increased lipid peroxidation. However, post-treatment with O-Vanillin effectively mitigated these toxic effects, preserving antioxidant capacities and preventing lipid peroxidation. Additionally, O-Vanillin prevented the loss of body weight and improved cocoon characteristics. At the histological level, spinetoram exposure caused mild histological damage in the gut, fat body, and silk gland. However, O-Vanillin post-treatment had ameliorative effects and mitigated the histological damages. To delve deeper into the mechanism of amelioration of O-Vanillin, in silico studies were used to study the interaction between an important xenobiotic metabolism protein of theBombyxmori, i.e., Cytochrome p450, specifically CYP9A19, and O-Vanillin. We performed blind molecular docking followed by molecular dynamic simulation, and the results demonstrated stable binding interactions between O-Vanillin and CYP9A19, a cytochrome P450 protein in silkworm, belonging to the subfamily CYP9A, suggesting a potential role for O-vanillin in modulating xenobiotic metabolism.