Effects of Heat Stress-Induced Sex Hormone Dysregulation on Reproduction and Growth in Male Adolescents and Beneficial Foods.

Heat stress due to climate warming can significantly affect the synthesis of sex hormones in male adolescents, which can impair the ability of the hypothalamus to secrete gonadotropin-releasing hormone on the hypothalamic-pituitary-gonadal axis, which leads to a decrease in luteinizing hormone and follicle-stimulating hormone, which ultimately negatively affects spermatogenesis and testosterone synthesis. For optimal spermatogenesis, the testicular temperature should be 2-6 °C lower than body temperature. Heat stress directly affects the testes, damaging them and reducing testosterone synthesis. Additionally, chronic heat stress abnormally increases the level of aromatase in Leydig cells, which increases estradiol synthesis while decreasing testosterone, leading to an imbalance of sex hormones and spermatogenesis failure. Low levels of testosterone in male adolescents lead to delayed puberty and incomplete sexual maturation, negatively affect height growth and bone mineral density, and can lead to a decrease in lean body mass and an increase in fat mass. In order for male adolescents to acquire healthy reproductive capacity, it is recommended to provide sufficient nutrition and energy, avoid exposure to heat stress, and provide foods and supplements to prevent or repair testosterone reduction, germ cell damage, and sperm count reduction caused by heat stress so that they can enter a healthy adulthood.

Comparative analysis of cyto-genotoxicity of zinc using the comet assay and chromosomal abnormality test.

In this study, the toxicity of the trace element zinc (Zn) in Allium cepa L. test material was examined. Toxicity was investigated in terms of physiological, cytogenetic, biochemical, and anatomical aspects. Germination percentage, root length, weight gain, mitotic index (MI), micronucleus (MN) frequency, chromosomal abnormalities (CAs), malondialdehyde (MDA), proline and chlorophyll levels, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and meristematic cell damage were used as indicators of toxicity. Additionally, the comet test was used to measure the degree of DNA damage. Four groups of A. cepa bulbs-one for control and three for applications-were created. While the bulbs in the treatment groups were germinated with Zn at concentrations of 35, 70, and 140 mg/L, the bulbs in the control group were germinated with tap water. Germination was carried out at room temperature for 72 h and 144 h. When the allotted time was over, the root tips and leaf samples were collected and prepared for spectrophotometric measurements and macroscopic-microscopic examinations. Consequently, Zn treatment led to significant reductions in physiological indicators such as weight gain, root length, and germination percentage. Zn exposure caused genotoxicity by decreasing the MI ratios and increasing the frequency of MN and CAs (p < 0.05). Zn promoted various types of CAs in root tip cells. The most observed of CAs was the sticky chromosome. Depending on the dose, Zn was found to cause an increase in tail lengths in comet analyses, which led to DNA damage. Exposure to Zn led to a significant decrease in chlorophyll levels and an increase in MDA and proline levels. It also promoted significant increases in SOD and CAT enzyme activities up to 70 mg/L dose and statistically significant decreases at 140 mg/L dose. Additionally, Zn exposure caused different types of anatomical damage. The most severe ones are epidermis and cortex cell damage. Besides, it was found that the Zn dose directly relates to all of the increases and decreases in physiological, cytogenetic, biochemical, and anatomical parameters that were seen as a result of Zn exposure. As a result, it has been determined that the Zn element, which is absolutely necessary in trace amounts for the continuation of the metabolic activities of the organisms, can cause toxicity if it reaches excessive levels.

Exercise training alleviates cholesterol and lipid accumulation in mice with non-alcoholic steatohepatitis: reduction of KMT2D-mediated histone methylation of IDI1.

Exercise training is a cornerstone treatment for non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the effects of exercises on lipid accumulation in non-alcoholic steatohepatitis (NASH) and to explore the molecular mechanism. Established NASH mice were remained sedentary or subjected to moderate-intensity continuous training or high-intensity interval training (HIIT). The two training regimens, especially the latter one, reduced liver weight, steatosis, inflammation, lipid accumulation, collagen deposition, and cholesterol content in the mouse liver. Similarly, the HIIT regimen improved clinical presentation of NAFLD patients. RNA sequencing analysis revealed lysine methyltransferase 2D (Kmt2d) and isopentenyl-diphosphate delta isomerase 1 (Idi1) as two important genes downregulated in mice underwent HIIT. By using mouse hepatocytes AML12, we found that KMT2D promoted Idi1 expression by catalyzing H3K4me1 modification near its promoter. Upregulation of either KMT2D or IDI1 blocked the ameliorating effects of HIIT on mice. Meanwhile, in AML12 cells modeled by palmitic acid and oleic acid treatment, KMT2D and IDI1 were found to be correlated with lipid accumulation, cholesterol content, inflammation, and cell death and senescence. In conclusion, this study demonstrates that the ameliorating effects of exercise training on NASH might involve the downregulation of the KMT2D/IDI1 axis.

LC-MS/MS phenolic profileand remedial role of Urtica dioica extract against Li2CO3-induced toxicity.

In this study, the protective role of Urtica dioica extract (Udex) against Li2CO3 toxicity in Allium cepa L. was investigated using various parameters such as germination rates, root growth, weight gain, mitotic index (MI), malondialdehyde (MDA), micronucleus (MN), antioxidant enzyme activity, chromosomal abnormalities (CAs) and anatomical changes. As the biological activity of Udex is related to its active content, the profile of phenolic compounds was determined by LC-MS/MS analysis. Li2CO3 caused abnormalities in the tested parameters and serious regressions in germination parameters. Application of 100 mg/L Li2CO3 reduced the chlorophyll a and b contents by 73.04% and 65.7%, respectively. Li2CO3 application exhibited a cytotoxic effect by inducing significant decreases in MI and increases in the frequency of MN, and also showed a genotoxic effect by causing CAs. After 100 mg/L Li2CO3 treatment, MDA, proline, superoxide dismutase, and catalase levels increased by 54.9%, 58.5%, 47.8%, and 52.3%, respectively. Li2CO3 and Udex co-administration resulted in a regression in increased biochemical parameters and genotoxicity parameters, and an improvement in germination parameters. Furthermore, Udex demonstrated efficacy in mitigating the detrimental effects of Li2CO3 on the root tip, particularly in the 200 µg/mL Udex-treated group. The thickening of the cortex cell wall and conduction tissue, which is commonly induced by Li2CO3, was not observed in the Udex-treated group. The protective effect of Udex can be explained by the phenolic compounds it contains. Rutin was detected as the major component in Udex and other phenolics were listed according to their presence rate as protecatechuic acid > caffeic acid > p-coumaric acid > syringic acid > rosemarinic acid > epicatechin. Li ions, which increase in the environment after industrialization, are an important environmental pollutant and exhibit toxicity that affects many pathways in organisms. Scientific research should not only detect these toxic effects but also develop solutions to such problems. In this study, it was determined that the Udex application had a toxicity-reducing role against Li2CO3 toxicity. Also, it has been demonstrated that A. cepa is an important indicator in determining this toxicity and toxicity-reducing applications.

Dexamethasone reduces cisplatin-induced hair cell damage by inducing cisplatin resistance through metallothionein-2.

PURPOSE: Hair cell damage is a common side effect caused by the anticancer drug cisplatin (CDDP), which reduces patient quality of life. One CDDP resistance mechanism that occurs in recurrent cancers is heavy metal detoxification by metallothionein-2 (mt2). Here, we show that in zebrafish larvae, dexamethasone (DEX) reduces CDDP-induced hair cell damage by enhancing mt2 expression. METHODS: Transgenic zebrafish (cldn: gfp; atoh1: rfp) that express green and red fluorescent proteins in neuromasts and hair cells, respectively, were used. The zebrafish were pretreated with DEX at 52 h post-fertilization (hpf) for 8 h, followed by CDDP treatment for 12 h. The lateral line hair cells of CDDP-treated zebrafish at 72 hpf were observed by fluorescence microscopy. RESULTS: Reporting odds ratio (ROR) analysis using an adverse event database indicated an association between a decrease in CDDP-induced ototoxicity and DEX as an antiemetic treatment for cancer chemotherapy. Pretreatment with DEX protected 72 hpf zebrafish hair cells from CDDP-induced damage. The expression of mt2 mRNA was significantly increased by the combination of 10 µM DEX with CDDP. Gene editing of mt2 reversed the protective effect of DEX against CDDP-induced damage in hair cells. CONCLUSION: DEX protects hair cells from CDDP-induced damage through increased mt2 expression, which is a resistance mechanism for platinum-based anticancer drugs.

Evaluation of destruction of bacterial membrane structure associated with anti-quorum sensing and ant-diabetic activity of Cyperus esculentus extract.

Recently, there has been an increasing demand for medicinal plants to control diseases for good health and well-being, as primary health facilities are inadequate in certain populations to cure infections. Since synthetic medicines are toxic to humans and other animals, the present research is thus focused on using traditional medicine for treating various ailments as they are harmless. Based on the above facts, the current study was conducted to assay the antimicrobial, anti-diabetic, anti-cholinesterase, anti-oxidant, anti-quorum sensing, and anti-antibiotic resistance modifying effect of extracts of Cyperus esculentus. This study found 37 and 30 chemicals in butanol and dichloromethane (DCM) extracts using a gas chromatograph mass spectrophotometer (GC-MS). Most active compounds identified were benzofuran, 2,3-dihydro-, 1,2,3-benzenetriol, 3-bornanone, oxime and oleic acid by extracts of butanol whereas dichloromethane extracted three major active compounds (2,3-dihydro-3,5-dihydroxy-, 4H-pyran-4-one 3-deoxy-d-mannoic lactone and 5-hydroxymethylfurfural). Both dichloromethane and butanol extracts showed the highest antimicrobial activity. Compared to aqueous extracts, dichloromethane, and butanol showed excellent anti-diabetic anti-cholinesterase activities and inhibited virulence factors regulated by quorum sensing (QS). Anti-oxidants increased in solvent extracts (DCM and butanol) compared to aqueous extracts. Results of scanning electron microscope (SEM) and Fourier Transmission Infrared (FTIR) indicated damage to the cell membrane of S. aureus by the formation of pits and breakage in functional groups exposed to the extracts of butanol and dichloromethane compared to aqueous extracts. The above results confirmed that C. esculentus can be an alternative medicine for treating diseases.

BRD4 absence inactivates endoplasmic reticulum stress to retard dehydroepiandrosterone-triggered ovarian granular cell apoptosis in polycystic ovary syndrome via GRP78.

Polycystic ovary syndrome (PCOS) is a hormonal disorder and significantly affects reproductive and metabolic function. Bromodomain-containing protein 4 (BRD4) is reported to promote ovarian fibrosis in PCOS. The present work was conducted to investigate the detailed role of BRD4 and the corresponding functional mechanism in PCOS. Functional experiments including CCK-8 method, EDU staining and TUNEL staining were used to detect the key cellular processes. Western blot examined the expression of BRD4, apoptosis- and endoplasmic reticulum stress (ERS)-associated proteins. HDOCK server predicted the binding of BRD4 with Glucose-Regulated Protein 78 (GRP78), which was validated by Co-IP assay. BRD4 expression was increased and ERS was activated in dehydroepiandrosterone (DHEA)-induced KGN cells. Inhibition of BRD4 improved the viability whereas it inhibited the apoptosis and ERS of KGN cells induced by DHEA. In addition, BRD4 bound to GRP78. GRP78 elevation or ERS activator tunicamycin (TM) partly abolished the impacts of BRD4 silencing on the ERS, proliferation and apoptosis in DHEA-treated KGN cells. Anyway, knockdown of BRD4 may reduce DHEA-induced ovarian granular cell damage in PCOS via inactivating GRP78-mediated ERS.

Remarkable improvement of symptoms and signs of severe dry eye treated by ocular immersion hydrotherapy.

Key Clinical Message: Traditional treatment options are often insufficient in treating severe dry eyes caused by systemic diseases. This case demonstrates that ocular immersion hydrotherapy significantly alleviated symptoms and ocular surface inflammation in ocular graft-versus-host disease. Based on these findings, we propose it as a promising option for managing severe dry eye disease. Abstract: This case report investigates the efficacy of ocular immersion hydrotherapy (OIH) in treating severe dry eye secondary to ocular graft-versus-host disease (oGVHD). A 35-year-old female with a history of acute myeloid leukemia-M2 and subsequent hematopoietic stem cell transplantation (HSCT) developed high-intensity oGVHD unresponsive to conventional treatments, including topical corticosteroids and lubricants. We introduced OIH, utilizing sterilized swimming goggles filled with intraocular irrigating solutions, providing a moist microenvironment for the ocular surface. Symptoms were significantly relieved after treatment. Corneal filaments and epithelial defects were significantly reduced, and in vivo confocal microscopy (IVCM) demonstrated resolution of inflammation and reappearance of corneal nerves. This case indicates that OIH could be a promising therapeutic approach for severe dry eye conditions arising from oGVHD, particularly for patients refractory to traditional treatments. Further studies are warranted to elucidate the long-term benefits and mechanisms of OIH in oGVHD management.

H19 lncRNA triggers ferroptosis, exacerbating ox-LDL-induced artery endothelial cell damage in vitro.

BACKGROUND: The precise association between lncRNA H19 and ferroptosis in the context of atherosclerosis remains uncertain. OBJECTIVE: This study is to clarify the underlying process and propose novel approaches for the advancement of therapeutic interventions targeting atherosclerosis. METHODS: Assessment of ferroptosis, which entails the evaluation of cell viability using CCK-8 and the quantification of intracellular MDA, GSH, and ferrous ions. Simultaneously, the protein expression levels of assessed by western blot analysis, while the expression level of lncRNA H19 was also determined. Furthermore, HAECs that were cultured with ox-LDL were subjected to Fer-1 interference. HAECs were exposed to ox-LDL and then transfected with H19 shRNA and H19 overexpression vector pcDNA3.1. The level of ferroptosis in the cells was then measured. Then, HAECs were subjected to incubation with ox-LDL, followed by transfection with H19 shRNA and treated with Erastin to assess the levels of ferroptosis, cell viability, and inflammatory factor production. and the ability for blood vessel development. RESULTS: The survival rate of HAECs in the ox-LDL group was much lower. Ox-LDL resulted in an upregulation of ACSL4 expression in HAECs, while the expression of SLC7A11 and GPX4 decreased. CONCLUSIONS: lncRNA H19 enhances ferroptosis and exacerbates arterial endothelial cell damage induced by LDL.

Integrated remediation and detoxification of triclocarban-contaminated water using waste-derived biochar-immobilized cells by long-term column experiments.

Triclocarban (TCC), an antibacterial agent commonly used in personal care products, is one of the top ten contaminants of emerging concern in various environmental media, including soil and contaminated water in vadose zone. This study aimed to investigate TCC-contaminated water remediation using biochar-immobilized bacterial cells. Pseudomonas fluorescens strain MC46 (MC46), an efficient TCC-degrading isolate, was chosen, whereas agro-industrial carbonized waste as biochar was directly used as a sustainable cell immobilization carrier. According to the long-term TCC removal performance results (160 d), the biochar-immobilized cells consistently exhibited high TCC removal efficiencies (84-97%), whereas the free MC46 removed TCC for 76-94%. At 100 days, the detachment of the MC46 cells from the immobilized cell column was observed. The micro-Fourier-transform infrared spectroscopy results indicated that extracellular polymeric substance (EPS) was produced, but polysaccharide and protein fractions were washed out of the column. The lipid fraction of EPS adhered to the biochar, promoting TCC sorption for long-term treatment. The shortening of MC46 cells improved the tolerance of TCC toxicity. The TCC-contaminated water was successfully detoxified by the biochar-immobilized MC46 cells. Overall, the waste-derived biochar-immobilized cell system proposed in this study for the removal of emerging contaminants, including TCC, is efficient, economical, and aligned with the sustainable development concept of value-added utilization of waste.

Application of self-assembly palladium single-atom nanozyme over polyoxometalates in protection against neomycin-induced hearing loss by inhibiting ferroptosis.

Deafness mainly results from irreversible impairment of hair cells (HCs), which may relate to oxidative stress, yet therapeutical solutions is lacked due to limited understanding on the exact molecular mechanism. Herein, mimicking the molecular structure of natural enzymes, a palladium (Pd) single-atom nanozyme (SAN) was fabricated, exhibiting superoxide dismutase and catalase activity, transforming reactive oxygen species (ROS) into O2 and H2O. We examined the involvement of Pd in neomycin-induced HCs loss in vitro and in vivo over zebrafish. Our results revealed that neomycin treatment induced apoptosis in HCs, resulting in substantial of ROS elevation in HEI-OC1 cells, decrease in mitochondrial membrane potential, and increase in lipid peroxidation and iron accumulation, ultimately leading to iron-mediated cell death. Noteworthy, Pd SAN treatment exhibited significant protective effects against HCs damage and impaired HCs function in zebrafish by inhibiting ferroptosis. Furthermore, the application of iron death inducer RSL3 resulted in notable exacerbation of neomycin-induced harm, which was mitigated by Pd administration. Our investigation demonstrates that antioxidants is promising for inhibiting ferroptosis and repairing of mitochondrial function in HCs and the enzyme-mimic SAN provides a good strategy for designing drugs alleviating neomycin-induced ototoxicity.

Impact of Polyethylene Terephthalate Microplastics on Drosophila melanogaster Biological Profiles and Heat Shock Protein Levels.

Microplastics and nanoplastics are abundant in the environment. Further research is necessary to examine the consequences of microplastic contamination on living species, given its widespread presence. In our research, we determined the toxic effects of PET microplastics on Drosophila melanogaster at the cellular and genetic levels. Our study revealed severe cytotoxicity in the midgut of larvae and the induction of oxidative stress after 24 and 48 h of treatment, as indicated by the total protein, Cu-Zn SOD, CAT, and MDA contents. For the first time, cell damage in the reproductive parts of the ovaries of female flies, as well as in the accessory glands and testes of male flies, has been observed. Furthermore, a decline in reproductive health was noted, resulting in decreased fertility among the flies. By analyzing stress-related genes such as hsp83, hsp70, hsp60, and hsp26, we detected elevated expression of hsp83 and hsp70. Our study identified hsp83 as a specific biomarker for detecting early redox changes in cells caused by PET microplastics in all the treated groups, helping to elucidate the primary defense mechanism against PET microplastic toxicity. This study offers foundational insights into the emerging environmental threats posed by microplastics, revealing discernible alterations at the genetic level.

Protective effect of short-chain fructo-oligosaccharides from chicory on alcohol-induced injury in GES-1 cells via Keap1/Nrf2 and NLRP3 inflammasome signaling pathways.

Numerous studies have demonstrated that polysaccharides derived from chicory possess the ability to regulate host signaling and modify mucosal damage. Yet, the effect and mechanism of short-chain fructo-oligosaccharides (scFOS) on gastric mucosa remain unclear. Hence, the protective effect of three scFOS (1-Kestose, Nystose, and 1F-Fructofuranosylnystose) against ethanol-induced injury in gastric epithelial (GES-1) cells, and the underlying molecular mechanism involved was investigated in this study. Treatment with 7% ethanol decreased the cell viability of GES-1 cells, resulting in oxidative stress and inflammation. However, pretreatment with scFOS exhibited significant improvements in cell viability, and mitigated oxidative stress and inflammation. scFOS markedly elevated the protein expression of Nrf2, HO-1, SOD1 and SOD2, while suppressing the expression of Keap1. scFOS pretreatment could also maintain mitochondrial membrane potential balance and reduce apoptosis. In addition, scFOS was observed to reduce the protein level of NLRP3, Caspase-1 and ASC. In conclusion, scFOS served a preventive function in mitigating oxidative stress and inflammation in ethanol-exposed GES-1 cells through modulation of the Keap1/Nrf2 and NLRP3 inflammasome signaling pathways. Collectively, the results indicated that scFOS could significantly mitigate ethanol-induced gastric cell damage, suggesting its potential for safeguarding gastrointestinal health.

Nanowire-assisted electroporation via inducing cell destruction for inhibiting formation of VBNC bacteria: Comparison with chlorination.

The induction of viable but nonculturable (VBNC) bacteria with cellular integrity and low metabolic activity by chemical disinfection causes a significant underestimation of potential microbiological risks in drinking water. Herein, a physical Co3O4 nanowire-assisted electroporation (NW-EP) was developed to induce cell damage via the locally enhanced electric field over nanowire tips, potentially achieving effective inhibition of VBNC cells as compared with chemical chlorination (Cl2). NW-EP enabled over 5-log removal of culturable cell for various G+/G- bacteria under voltage of 1.0 V and hydraulic retention time of 180 s, and with ∼3-6 times lower energy consumption than Cl2. NW-EP also achieved much higher removals (∼84.6 % and 89.5 %) of viable Bacillus cereus (G+) and Acinetobacter schindleri (G-) via generating unrecoverable pores on cell wall and reversible/irreversible pores on cell membrane than Cl2 (∼28.6 % and 41.1 %) with insignificant cell damage. The residual VBNC bacteria with cell wall damage and membrane pore resealing exhibited gradual inactivation by osmotic stress, leading to ∼99.8 % cell inactivation after 24 h storage (∼59.4 % for Cl2). Characterizations of cell membrane integrity and cell morphology revealed that osmotic stress promoted cell membrane damage for the gradual inactivation of VBNC cells during storage. The excellent adaptability of NW-EP for controlling VBNC cells in DI, tap and lake waters suggested its promising application potentials for drinking water, such as design of an external device on household taps.

MPoMA protects against lung epithelial cell injury via p65 degradation.

Numerous cases of lung injury caused by viral infection were reported during the coronavirus disease-19 pandemic. While there have been significant efforts to develop drugs that block viral infection and spread, the development of drugs to reduce or reverse lung injury has been a lower priority. This study aimed to identify compounds from a library of compounds that prevent viral infection that could reduce and prevent lung epithelial cell damage. We investigated the cytotoxicity of the compounds, their activity in inhibiting viral spike protein binding to cells, and their activity in reducing IL-8 production in lung epithelial cells damaged by amodiaquine (AQ). We identified N-(4-(4-methoxyphenoxy)-3-methylphenyl)-N-methylacetamide (MPoMA) as a non-cytotoxic inhibitor against viral infection and AQ-induced cell damage. MPoMA inhibited the expression of IL-8, IL-6, IL-1ß, and fibronectin induced by AQ and protected against AQ-induced morphological changes. However, MPoMA did not affect basal IL-8 expression in lung epithelial cells in the absence of AQ. Further mechanistic analysis confirmed that MPoMA selectively promoted the proteasomal degradation of inflammatory mediator p65, thereby reducing intracellular p65 expression and p65-mediated inflammatory responses. MPoMA exerted potent anti-inflammatory and protective functions in epithelial cells against LPS-induced acute lung injury in vivo. These findings suggest that MPoMA may have beneficial effects in suppressing viral infection and preventing lung epithelial cell damage through the degradation of p65 and inhibition of the production of inflammatory cytokines.

Schisandrin B protect inner hair cells from cisplatin by inhibiting celluar oxidative stress and apoptosis.

Cisplatin is an effective chemotherapeutic agent; however, ototoxicity is one of its negative effects that greatly limits the use of cisplatin in clinical settings. Previous research has shown that the most important process cisplatin damage to inner ear cells, such as hair cells (HCs), is the excessive production and accumulation of ROS. Schisandrin B (SchB), is a low-toxicity, inexpensive, naturally occurring antioxidant with a variety of pharmacological effects. Therefore, the potential antioxidant effects of SchB may be useful for cisplatin ototoxicity treatment. In this study, the effects of SchB on cochlear hair cell viability, ROS levels, and expression of apoptosis-related molecules were evaluated by CCK-8, immunofluorescence, flow cytometry, and qRT-PCR, as well as auditory brainstem response (ABR) and dysmorphic product otoacoustic emission (DPOAE) tests to assess the effects on inner ear function. The results showed that SchB treatment increased cell survival, prevented apoptosis, and reduced cisplatin-induced ROS formation. SchB treatment reduced the loss of cochlear HCs caused by cisplatin in exosome culture. In addition, SchB treatment attenuated cisplatin-induced hearing loss and HC loss in mice. This study demonstrates the ability of SchB to inhibit cochlear hair cell apoptosis and ROS generation and shows its potential therapeutic effect on cisplatin ototoxicity.

Ototoxicity among cisplatin, carboplatin, and oxaliplatin in zebrafish model.

Platinum-based antineoplastic drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various cancers. Ototoxicity is a common adverse effect of platinum-based drugs. Ototoxicity leads to irreversible hearing impairment. We hypothesize that different platinum-based drugs exhibit varying ototoxic concentrations, time effects, and ototoxic mechanisms. We tested this hypothesis by using a zebrafish model (pvalb3b: TagGFP) to assess the viability of hair cells collected from zebrafish larvae. Cisplatin, carboplatin, and oxaliplatin were administered at dosages of 100, 200, or 400 µM, and the ototoxic effects of these drugs were assessed 1, 2, or 3 h after administration. Fm4-64 and a TUNEL assay were used to label the membranes of living hair cells and to detect cell apoptosis, respectively. We observed that >50% of hair cells were damaged at 1 h after cisplatin (100 µM) exposure, and this ototoxic effect increased at higher dosages and over time. Owing to the smaller ototoxic effects of carboplatin and oxaliplatin, we conducted higher-strength and longer-duration experiments with these drugs. Neither carboplatin nor oxaliplatin was obviously ototoxic, even at 1600 µM and after 6 h. Moreover, only cisplatin damaged the membranes of the hair cells. Cell apoptosis and significantly increased antioxidant gene expression were observed in only the cisplatin group. In conclusion, cisplatin significantly damages sensory hair cells and has notable dosage and time effects. Carboplatin and oxaliplatin are less ototoxic than cisplatin, likely due to having different ototoxic mechanisms than cisplatin.

DAMPs and DAMP-sensing receptors in inflammation and diseases.

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules produced in cellular damage or stress, and they can activate the innate immune system. DAMPs contain multiple types of molecules, including nucleic acids, proteins, ions, glycans, and metabolites. Although these endogenous molecules do not trigger immune response under steady-state condition, they may undergo changes in distribution, physical or chemical property, or concentration upon cellular damage or stress, and then they become DAMPs that can be sensed by innate immune receptors to induce inflammatory response. Thus, DAMPs play an important role in inflammation and inflammatory diseases. In this review, we summarize the conversion of homeostatic molecules into DAMPs; the diverse nature and classification, cellular origin, and sensing of DAMPs; and their role in inflammation and related diseases. Furthermore, we discuss the clinical strategies to treat DAMP-associated diseases via targeting DAMP-sensing receptors.

Investigation of multidirectional toxicity induced by high-dose molybdenum exposure with Allium test.

In this study, the multifaceted toxicity induced by high doses of the essential trace element molybdenum in Allium cepa L. was investigated. Germination, root elongation, weight gain, mitotic index (MI), micronucleus (MN), chromosomal abnormalities (CAs), Comet assay, malondialdehyde (MDA), proline, superoxide dismutase (SOD), catalase (CAT) and anatomical parameters were used as biomarkers of toxicity. In addition, detailed correlation and PCA analyzes were performed for all parameters discussed. On the other hand, this study focused on the development of a two hidden layer deep neural network (DNN) using Matlab. Four experimental groups were designed: control group bulbs were germinated in tap water and application group bulbs were germinated with 1000, 2000 and 4000 mg/L doses of molybdenum for 72 h. After germination, root tips were collected and prepared for analysis. As a result, molybdenum exposure caused a dose-dependent decrease (p < 0.05) in the investigated physiological parameter values, and an increase (p < 0.05) in the cytogenetic (except MI) and biochemical parameter values. Molybdenum exposure induced different types of CAs and various anatomical damages in root meristem cells. Comet assay results showed that the severity of DNA damage increased depending on the increasing molybdenum dose. Detailed correlation and PCA analysis results determined significant positive and negative interactions between the investigated parameters and confirmed the relationships of these parameters with molybdenum doses. It has been found that the DNN model is in close agreement with the actual data showing the accuracy of the predictions. MAE, MAPE, RMSE and R2 were used to evaluate the effectiveness of the DNN model. Collective analysis of these metrics showed that the DNN model performed well. As a result, it has been determined once again that high doses of molybdenum cause multiple toxicity in A. cepa and the Allium test is a reliable universal test for determining this toxicity. Therefore, periodic measurement of molybdenum levels in agricultural soils should be the first priority in preventing molybdenum toxicity.

Exploring the relationships between physiochemical properties of nanoparticles and cell damage to combat cancer growth using simple periodic table-based descriptors.

A comprehensive knowledge of the physical and chemical properties of nanomaterials (NMs) is necessary to design them effectively for regulated use. Although NMs are utilized in therapeutics, their cytotoxicity has attracted great attention. Nanoscale quantitative structure-property relationship (nano-QSPR) models can help in understanding the relationship between NMs and the biological environment and provide new ways for modeling the structural properties and bio-toxic effects of NMs. The goal of the study is to construct fully validated property-based models to extract relevant features for estimating and influencing the zeta potential and obtaining the toxicity profile regarding cell damage in the treatment of cancer cells. To achieve this, QSPR modeling was first performed with 18 metal oxide (MeOx) NMs to measure their materials properties using periodic table-based descriptors. The features obtained were later applied for zeta potential calculation (imputation for sparse data) for MeOx NMs that lack such information. To further clarify the influence of the zeta potential on cell damage, a QSPR model was developed with 132 MeOx NMs to understand the possible mechanisms of cell damage. The results showed that zeta potential, along with seven other descriptors, had the potential to influence oxidative damage through free radical accumulation, which could lead to changes in the survival rate of cancerous cells. The developed QSPR and quantitative structure-activity relationship models also give hints regarding safer design and toxicity assessment of MeOx NMs.