Effects of intratesticular injection of hypertonic mannitol and saline on the quality of donkey sperm, indicators of oxidative stress and testicular tissue pathology.

OBJECTIVES: The aim of the present study was to examine donkey sperm quality after intratesticular injection of hypertonic mannitol (HM) and saline (HS). METHODS: Randomly assigned to five treatment groups were 15 adult male donkeys: (1) Control group (no treatment), (2) Surgery group (surgical castration for testosterone control), (3) NS group (normal saline intratesticular injection), (4) HS group (hypertonic saline), and (5) HM group. We injected 20 mL per testicle. We took 5 mL blood from all donkeys before injection. Castration was performed under general anesthesia 60 days later. Samples included blood and testicular tissue. Total motility (TM), progressive motility (PM), movementy features, DNA damage, morphology, viability, and plasma membrane functionality were evaluated. Hormone analyses, histomorphometric studies and oxidative stress indices including total antioxidant capacity (TAC), glutathione peroxidase (GPx), glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and NADP+/NADPH were evaluated. Apoptosis, pyroptosis-related Bax, Caspase-1, GSDMD, and Bcl-2 expression were also assessed. RESULTS: In HS and HM groups, testosterone, epididymal sperm count, motility, viability, and plasma membrane functionality dropped while sperm DNA damage increased. HS and HM groups had significantly lower histomorphometric parameters, TAC, GPx, SOD, GSH, and Bcl-2 gene expression. MDA, NADP+/NADPH, Bax, Caspase-1, and GSDMD gene expression were substantially higher in the HS and HM groups than in the control group. CONCLUSIONS: Toxic effects of hypertonic saline and mannitol on reproductive parameters were seen following, hence, they might be considered as a good chemical sterilizing treatment in donkeys.

Quercetin Improves Barrier Properties in Porcine Small Intestine but Not in Peyer's Patches.

Peyer's patches (PPs) are part of the gut-associated lymphatic tissue (GALT) and represent the first line of the intestinal immunological defense. They consist of follicles with lymphocytes and an overlying subepithelial dome with dendritic cells and macrophages, and they are covered by the follicle-associated epithelium (FAE). A sealed paracellular pathway in the FAE is crucial for the controlled uptake of luminal antigens. Quercetin is the most abundant plant flavonoid and has a barrier-strengthening effect on tight junctions (TJs), a protein complex that regulates the paracellular pathway. In this study, we aimed to analyze the effect of quercetin on porcine PPs and the surrounding villus epithelium (VE). We incubated both tissue types for 4 h in Ussing chambers, recorded the transepithelial electrical resistance (TEER), and measured the unidirectional tracer flux of [3H]-mannitol. Subsequently, we analyzed the expression, protein amount, and localization of three TJ proteins, claudin 1, claudin 2, and claudin 4. In the PPs, we could not detect an effect of quercetin after 4 h, neither on TEER nor on the [3H]-mannitol flux. In the VE, quercetin led to a higher TEER value, while the [3H]-mannitol flux was unchanged. The pore-forming claudin 2 was decreased while the barrier-forming claudin 4 was increased and the expression was upregulated. Claudin 1 was unchanged and all claudins could be located in the paracellular membrane by immunofluorescence microscopy. Our study shows the barrier-strengthening effect of quercetin in porcine VE by claudin 4 upregulation and a claudin 2 decrease. Moreover, it underlines the different barrier properties of PPs compared to the VE.

Effects of nonnutritive sugar inclusion in laboratory diets and attracticidal spheres on survivorship and mobility of 2 Dipteran species, Rhagoletis pomonella (Diptera: Tephritidae) and Drosophila suzukii (Diptera: Drosophilidae).

Native apple maggot fly, Rhagoletis pomonella, and invasive spotted-wing drosophila, Drosophila suzukii, are key pests of apple and small fruit, respectively, in the United States. Both species are typically managed with standard insecticide applications. However, interest in alternative strategies that result in insecticide reductions has led to evaluations of nonnutritive sugars as toxicants for Drosophila species and development of attracticidal spheres for both species. Here, we evaluated the survivorship of R. pomonella and D. suzukii when provided with standard diets that substituted saccharin, sucralose, aspartame, erythritol, dextrose, or mannitol for the sucrose component and compared them with standard diets and water-only controls for up to 15 days. Presence of erythritol and mannitol significantly decreased survivorship of R. pomonella and erythritol significantly decreased the survivorship of D. suzukii. However, mobility trials following a 2 h exposure to aqueous solutions of each sugar treatment resulted in no strong impact on either species. Survivorship after 30 min exposure to erythritol or mannitol alone, or in combination with varying concentrations of sucrose (serving as a phagostimulant) at 30 min and 24 h were evaluated for both species. Only D. suzukii survivorship was affected with decreased survivorship on erythritol:sucrose solutions of 20:0% and 15:5% for 24 h. Based on all results, erythritol appeared most promising, and was integrated into attracticidal spheres as a toxicant but even at the highest concentration, survivorship remained unaffected for either species, thus making this nonnutritive sugar impractical and ineffective as a toxicant substitute in attracticidal spheres.

Mannitol inhibits the proliferation of neural stem cell by a p38 mitogen-activated protein kinase-dependent signaling pathway.

PURPOSE: Mannitol is one of the first-line drugs for reducing cerebral edema through increasing the extracellular osmotic pressure. However, long-term administration of mannitol in the treatment of cerebral edema triggers damage to neurons and astrocytes. Given that neural stem cell (NSC) is a subpopulation of main regenerative cells in the central nervous system after injury, the effect of mannitol on NSC is still elusive. The present study aims to elucidate the role of mannitol in NSC proliferation. METHODS: C57 mice were derived from the animal house of Zunyi Medical University. A total of 15 pregnant mice were employed for the purpose of isolating NSCs in this investigation. Initially, mouse primary NSCs were isolated from the embryonic cortex of mice and subsequently identified through immunofluorescence staining. In order to investigate the impact of mannitol on NSC proliferation, both cell counting kit-8 assays and neurospheres formation assays were conducted. The in vitro effects of mannitol were examined at various doses and time points. In order to elucidate the role of Aquaporin 4 (AQP4) in the suppressive effect of mannitol on NSC proliferation, various assays including reverse transcription polymerase chain reaction, western blotting, and immunocytochemistry were conducted on control and mannitol-treated groups. Additionally, the phosphorylated p38 (p-p38) was examined to explore the potential mechanism underlying the inhibitory effect of mannitol on NSC proliferation. Finally, to further confirm the involvement of the p38 mitogen-activated protein kinase-dependent (MAPK) signaling pathway in the observed inhibition of NSC proliferation by mannitol, SB203580 was employed. All data were analyzed using SPSS 20.0 software (SPSS, Inc., Chicago, IL). The statistical analysis among multiple comparisons was performed using one-way analysis of variance (ANOVA), followed by Turkey's post hoc test in case of the data following a normal distribution using a Shapiro-Wilk normality test. Comparisons between 2 groups were determined using Student's t-test, if the data exhibited a normal distribution using a Shapiro-Wilk normality test. Meanwhile, data were shown as median and interquartile range and analyzed using the Mann-Whitney U test, if the data failed the normality test. A p < 0.05 was considered as significant difference. RESULTS: Primary NSC were isolated from the mice, and the characteristics were identified using immunostaining analysis. Thereafter, the results indicated that mannitol held the capability of inhibiting NSC proliferation in a dose-dependent and time-dependent manner using cell counting kit-8, neurospheres formation, and immunostaining of Nestin and Ki67 assays. During the process of mannitol suppressing NSC proliferation, the expression of AQP4 mRNA and protein was downregulated, while the gene expression of p-p38 was elevated by reverse transcription polymerase chain reaction, immunostaining, and western blotting assays. Subsequently, the administration of SB203580, one of the p38 MAPK signaling pathway inhibitors, partially abrogated this inhibitory effect resulting from mannitol, supporting the fact that the p38 MAPK signaling pathway participated in curbing NSC proliferation induced by mannitol. CONCLUSIONS: Mannitol inhibits NSC proliferation through downregulating AQP4, while upregulating the expression of p-p38 MAPK.

Improved cardioprotective effect of 3-nitro-N-methyl salicylamide solution after a prolonged preservation time of rat heart.

Ischemic reperfusion injury, caused by oxidative stress during reperfusion, is an inevitable outcome of organ transplantation, especially when the organ preservation time is prolonged. Prolonged ischaemic preservation is a valuable technique for improving the success of organ transplantation, but numerous challenges remain. 3-nitro-N-methyl salicylamide (3-NNMS), an inhibitor of mitochondrial electron transport chain complex III, can be used to reduce reactive oxygen species production during blood reperfusion by slowing the electron flow rate of the respiratory chain. Based on this property, a novel preservation solution was developed for the preservation of isolated rat heart and its cardioprotective effect was investigated during an 8-h cold ischaemia preservation time for the first time. For comparison, 3-NNMS was also included in the histidine-tryptophan-ketoglutarate (HTK) solution. Compared to HTK, HTK supplemented with 3-NNMS significantly improved the heart rate of isolated rat hearts after 8 h of cold storage. Both 3-NNMS solution and HTK supplemented with 3-NNMS solution decreased cardiac troponin T and lactate dehydrogenase levels in perfusion fluid and reduced reactive oxygen species and malondialdehyde levels in the myocardium. The 3-NNMS also maintained the membrane potential of myocardial mitochondria and significantly increased superoxide dismutase levels. These results showed that the new 3-NNMS solution can protect mitochondrial and cardiomyocyte function by increasing antioxidant capacity and reducing oxidative stress in cryopreserved rat hearts during a prolonged preservation time, resulting in less myocardial injury and better heart rate.

Genome-Wide Analysis of Stress-Responsive Genes and Alternative Splice Variants in Arabidopsis Roots under Osmotic Stresses.

Plant roots show distinct gene-expression profiles from those of shoots under abiotic stress conditions. In this study, we performed mRNA sequencing (mRNA-Seq) to analyze the transcriptional profiling of Arabidopsis roots under osmotic stress conditions-high salinity (NaCl) and drought (mannitol). The roots demonstrated significantly distinct gene-expression changes from those of the aerial parts under both the NaCl and the mannitol treatment. We identified 68 closely connected transcription-factor genes involved in osmotic stress-signal transduction in roots. Well-known abscisic acid (ABA)-dependent and/or ABA-independent osmotic stress-responsive genes were not considerably upregulated in the roots compared to those in the aerial parts, indicating that the osmotic stress response in the roots may be regulated by other uncharacterized stress pathways. Moreover, we identified 26 osmotic-stress-responsive genes with distinct expressions of alternative splice variants in the roots. The quantitative reverse-transcription polymerase chain reaction further confirmed that alternative splice variants, such as those for ANNAT4, MAGL6, TRM19, and CAD9, were differentially expressed in the roots, suggesting that alternative splicing is an important regulatory mechanism in the osmotic stress response in roots. Altogether, our results suggest that tightly connected transcription-factor families, as well as alternative splicing and the resulting splice variants, are involved in the osmotic stress response in roots.

Effectiveness of curcumin-based antimicrobial photodynamic therapy against Staphylococcus aureus.

PURPOSE: This study investigated the effectiveness of curcumin-based antimicrobial photodynamic therapy (aPDT) against Staphylococcus aureus (S. aureus), the causative agent of ventilator-associated pneumonia. METHODS: Curcumin was added to S. aureus culture medium at concentrations of 25, 2.5, and 0.25 µM. After 60 min (20-25°C), each culture was irradiated for 1 and 3 min, and viable bacteria were counted. Curcumin (25 µM) was also added to a bacterial suspension with D-mannitol and sodium azide; microbial counts were determined after irradiation for 3 min. RESULTS: S. aureus was significantly reduced in the 1-min (P = 0.043) and 3-min (P = 0.011) irradiation groups in comparison to the 0-min irradiation group with 25 µM curcumin. No significant differences were observed between the curcumin alone group and the curcumin plus D-mannitol or sodium azide group. CONCLUSION: The findings of this study indicate that prolonged exposure (≥1 min) of S. aureus to LED in 25 µM curcumin solution induces cell wall injury. Curcumin-based aPDT as an adjunct to conventional oral care, employing existing dentistry equipment, offers a promising approach that does not rely on antimicrobial drugs or allows the emergence of resistant bacterial strains. This suggests its potential role in future strategies aimed at preventing ventilator-associated pneumonia.

Morphology as indicator of adaptive changes of model tissues in osmotically and chemically changing environments.

We investigate the formation and maintenance of the homeostatic state in the case of 2D epithelial tissues following an induction of hyperosmotic conditions, using media enriched with 80 to 320 mOsm of mannitol, NaCl, and urea. We characterise the changes in the tissue immediately after the osmotic shock, and follow it until the new homeostatic state is formed. We characterise changes in cooperative motility and proliferation pressure in the tissue upon treatment with the help of a theoretical model based on the delayed Fisher-Kolmogorov formalism, where the delay in density evolution is induced by the the finite time of the cell division. Finally we explore the adaptation of the homeostatic tissue to highly elevated osmotic conditions by evaluating the morphology and topology of cells after 20 days in incubation. We find that hyperosmotic environments together with changes in the extracellular matrix induce different mechanical states in viable tissues, where only some remain functional. The perspective is a relation between tissue topology and function, which could be explored beyond the scope of this manuscript. Experimental investigation of morphological effect of change of osmotic conditions on long-term tissue morphology and topology Effect of osmotic changes on transient tissue growth behaviour Analysis of recovery process of tissues post-osmotic-shock Toxicity limits of osmolytes in mid- to long-term tissue evolution Tissue adaptation to physiological changes in environment Long-term tissue stabilisation under altered osmotic conditions.

Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

CaCP15 Gene Negatively Regulates Salt and Osmotic Stress Responses in Capsicum annuum L.

Salt and osmotic stress seriously restrict the growth, development, and productivity of horticultural crops in the greenhouse. The papain-like cysteine proteases (PLCPs) participate in multi-stress responses in plants. We previously demonstrated that salt and osmotic stress affect cysteine protease 15 of pepper (Capsicum annuum L.) (CaCP15); however, the role of CaCP15 in salt and osmotic stress responses is unknown. Here, the function of CaCP15 in regulating pepper salt and osmotic stress resistance was explored. Pepper plants were subjected to abiotic (sodium chloride, mannitol, salicylic acid, ethrel, methyl jasmonate, etc.) and biotic stress (Phytophthora capsici inoculation). The CaCP15 was silenced through the virus-induced gene silencing (VIGS) and transiently overexpressed in pepper plants. The full-length CaCP15 fragment is 1568 bp, with an open reading frame of 1032 bp, encoding a 343 amino acid protein. CaCP15 is a senescence-associated gene 12 (SAG12) subfamily member containing two highly conserved domains, Inhibitor 129 and Peptidase_C1. CaCP15 expression was the highest in the stems of pepper plants. The expression was induced by salicylic acid, ethrel, methyl jasmonate, and was infected by Phytophthora capsici inoculation. Furthermore, CaCP15 was upregulated under salt and osmotic stress, and CaCP15 silencing in pepper enhanced salt and mannitol stress resistance. Conversely, transient overexpression of CaCP15 increased the sensitivity to salt and osmotic stress by reducing the antioxidant enzyme activities and negatively regulating the stress-related genes. This study indicates that CaCP15 negatively regulates salt and osmotic stress resistance in pepper via the ROS-scavenging.

Defining the contractile prostanoid component in hyperosmolar-induced bronchoconstriction in human small airways.

Exercise-induced bronchoconstriction (EIB) is thought to be triggered by increased osmolarity at the airway epithelium. The aim of this study was to define the contractile prostanoid component of EIB, using an ex vivo model where intact segments of bronchi (inner diameter 0.5-2 mm) isolated from human lung tissue and subjected to mannitol. Exposure of bronchial segments to hyperosmolar mannitol evoked a contraction (64.3 ± 3.5 %) which could be prevented either by elimination of mast cells (15.8 ± 4.3 %) or a combination of cysteinyl leukotriene (cysLT1), histamine (H1) and thromboxane (TP) receptor antagonists (11.2 ± 2.3 %). Likewise, when antagonism of TP receptor was exchanged for inhibition of either cyclooxygenase-1 (8 ± 2.5 %), hematopoietic prostaglandin (PG)D synthase (20.7 ± 5.6 %), TXA synthase (14.8 ± 4.9 %), or the combination of the latter two (12.2 ± 4.6 %), the mannitol-induced contraction was prevented, suggesting that the TP-mediated component is induced by PGD2 and TXA2 generated by COX-1 and their respective synthases.

Initial Diagnosis and Management of Acutely Elevated Intracranial Pressure.

Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recommendations may not apply to other causes. In the acute setting, management decisions must often be made before the underlying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We synthesize various guidelines and expert recommendations and identify core management principles including noninvasive maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine, corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the definitive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these time-sensitive, critical presentations in their initial stages.

Comparison of Equiosmolar Doses of 7.5% Hypertonic Saline and 20% Mannitol on Cerebral Oxygenation Status and Release of Brain Injury Markers During Supratentorial Craniotomy: A Randomized Controlled Trial.

BACKGROUND: Hyperosmolar therapy is the mainstay of treatment to reduce brain bulk and optimize surgical exposure during craniotomy. This study investigated the effect of equiosmolar doses of 7.5% hypertonic saline (HTS) and 20% mannitol on intraoperative cerebral oxygenation and metabolic status, systemic hemodynamics, brain relaxation, markers of cerebral injury, and perioperative craniotomy outcomes. METHODS: A total of 51 patients undergoing elective supratentorial craniotomy were randomly assigned to receive 7.5% HTS (2 mL/kg) or 20% mannitol (4.6 mL/kg) at scalp incision. Intraoperative arterial and jugular bulb blood samples were collected at predefined time intervals for assessment of various indices of cerebral oxygenation; multiple hemodynamic variables were concomitantly recorded. S100B protein and neuron-specific enolase levels were determined at baseline, and at 6 and 12 hours after surgery for assessment of neuronal injury. Brain relaxation and perioperative outcomes were also assessed. RESULTS: Demographic and intraoperative data, brain relaxation score, and perioperative outcomes were comparable between groups. Jugular bulb oxygen saturation and partial pressure of oxygen, arterial-jugular oxygen and carbon dioxide differences, and brain oxygen extraction ratio were favorably affected by 7.5% HTS up to 240 minutes postinfusion ( P <0.05), whereas mannitol was associated with only a short-lived (up to 15 min) improvement of these indices ( P <0.05). The changes in cerebral oxygenation corresponded to transient expansion of intravascular volume and improvements of cardiovascular performance. Increases in S100B and neuron-specific enolase levels at 6 and 12 hours after surgery ( P <0.0001) were comparable between groups. CONCLUSIONS: The conclusion is that 7.5% HTS has a more beneficial effect on cerebral oxygenation than an equiosmolar dose of 20% mannitol during supratentorial craniotomy, yet no clear-cut clinical superiority of either solution could be demonstrated.

The PICLS high-throughput screening method for agents extending cellular longevity identifies 2,5-anhydro-D-mannitol as novel anti-aging compound.

Although aging is the biggest risk factor for human chronic (cancer, diabetic, cardiovascular, and neurodegenerative) diseases, few interventions are known besides caloric restriction and a small number of drugs (with substantial side effects) that directly address aging. Thus, there is an urgent need for new options that can generally delay aging processes and prevent age-related diseases. Cellular aging is at the basis of aging processes. Chronological lifespan (CLS) of yeast Saccharomyces cerevisiae is the well-established model system for investigating the interventions of human post-mitotic cellular aging. CLS is defined as the number of days cells remain viable in a stationary phase. We developed a new, cheap, and fast quantitative method for measuring CLS in cell cultures incubated together with various chemical agents and controls on 96-well plates. Our PICLS protocol with (1) the use of propidium iodide for fluorescent-based cell survival reading in a microplate reader and (2) total cell count measurement via OD600nm absorption from the same plate provides real high-throughput capacity. Depending on logistics, large numbers of plates can be processed in parallel so that the screening of thousands of compounds becomes feasible in a short time. The method was validated by measuring the effect of rapamycin and calorie restriction on yeast CLS. We utilized this approach for chemical agent screening. We discovered the anti-aging/geroprotective potential of 2,5-anhydro-D-mannitol (2,5-AM) and suggest its usage individually or in combination with other anti-aging interventions.

Brain edema after oocyte retrieval: a case report.

BACKGROUND: Brain edema is a rare and serious complication of assisted reproductive technology (ART). The increased intracranial pressure and injured brain parenchyma are life-threatening and may even result in death. The pathogenesis may involve increased vascular permeability mediated by vascular endothelial growth factor and other vasoactive substances, including interleukin 6, interleukin 1ß, angiotensin II, insulin-like growth factor 1, transforming growth factor ß, and the renin-angiotensin system. CASE PRESENTATION: We presented a unique case report of a 29-year-old woman developed sudden irritability, blurred consciousness, and vomiting 8 h after oocyte retrieval. Blood examinations showed hyponatremia and cranial computed tomography showed swelling of the brain parenchyma. After therapeutic use of hypertonic saline and mannitol infusion, the patient's consciousness recovered and her neurological state improved. CONCLUSIONS: Brain edema is a rare and serious complication of ART. Quick infusion of hypertonic salt solution and mannitol is a key treatment. A good prognosis can be achieved after prompt treatment.

Manipulating the blood labyrinth barrier with mannitol to prevent cisplatin-induced hearing loss.

Cisplatin, a chemotherapeutic medication, remains in the cochlea indefinitely, causing permanent hearing loss. Mannitol, a diuretic medication, has been shown to increase the permeability of the blood labyrinth barrier (BLB). We hypothesize that mannitol increases the permeability of the BLB and therefore increases the rate of entry and egression of cisplatin and entry of otoprotective agents. Rats treated with cisplatin (t = 0) were given mannitol at either t = 0, t = 6 or t = 0,6 h. Another group of rats were treated with cisplatin with mannitol at 0 h and NAC/STS with and without mannitol at 6 h. Concurrent mannitol (t = 0) transiently increased cisplatin entry into the inner ear and exacerbated cisplatin-induced hearing loss. Delayed mannitol (t = 6) did not significantly increase cisplatin entry into the inner ear and preserved inner ear functionality and structure. Additional-delayed mannitol (t = 0,6) showed that the 2nd dose of mannitol prevented exacerbation of cisplatin with mannitol-induced hearing loss. A combination of delayed NAC/STS with mannitol (t = 6) was better than NAC/STS (t = 6) alone at providing partial to full protection against cisplatin with mannitol-induced hearing loss. In conclusion, mannitol injections at t = 6 h reduced cisplatin ototoxicity (instead of exacerbating cisplatin ototoxicity at t = 0 h), and it enhanced the otoprotective efficacy of antioxidants. This may provide an important therapeutic strategy to prevent cisplatin-induced hearing loss, a direct implication in protection against hearing loss in cisplatin chemotherapy.

Hypertonic saline for traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI. METHODS: This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA). RESULTS: Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors. CONCLUSION: HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates.

Functional proteomics identify mannitol metabolism in serum resistance and therapeutic implications in Vibrio alginolyticus.

Serum resistance is recognized as one of the most important pathogenic traits of bacterial pathogens, and no control measure is available. Based on our previous discovery that pathogenic Escherichia coli represses glycine, serine, and threonine metabolism to confer serum resistance and that the reactivation of this pathway by exogenous glycine could restore serum sensitivity, we further investigate the mechanism underlying the action of glycine in Vibrio alginolyticus. Thus, V. alginolyticus is treated with glycine, and the proteomic change is profiled with tandem mass tag-based quantitative proteomics. Compared to the control group, glycine treatment influences the expression of a total of 291 proteins. Among them, a trap-type mannitol/chloroaromatic compound transport system with periplasmic component, encoded by N646_0992, is the most significantly increased protein. In combination with the pathway enrichment analysis showing the altered fructose and mannitol metabolism, mannitol has emerged as a possible metabolite in enhancing the serum killing activity. To demonstrate this, exogenous mannitol reduces bacterial viability. This synergistic effect is further confirmed in a V. alginolyticus-Danio rerio infection model. Furthermore, the mechanism underlying mannitol-enabled serum killing is dependent on glycolysis and the pyruvate cycle that increases the deposition of complement components C3b and C5b-9 on the bacterial surface, whereas inhibiting glycolysis or the pyruvate cycle significantly weakened the synergistic effects and complement deposition. These data together suggest that mannitol is a potent metabolite in reversing the serum resistance of V. alginolyticus and has promising use in aquaculture.

A novel ABA-insensitive mutant in Arabidopsis reveals molecular network of ABA-induced anthocyanin accumulation and abiotic stress tolerance.

Abscisic acid (ABA) plays primary regulatory roles in abiotic stress tolerance and seed germination. Here, we report a unique novel Arabidopsis abscisic acid-insensitive mutant, abr (abscisic acid resistance), which was able to germinate in medium containing high ABA concentrations and tolerant to abiotic stress tolerance. We observed that abr mutant accumulated more anthocyanins by ABA treatment than did the wild type (WT). Dimethylthiourea (DMTU, an H2O2 scavenger) was effective in inhibiting ABA-induced anthocyanins accumulation. RNA-seq showed that the expression of anthocyanins synthesis, antioxidant enzyme and stress-related genes were specifically increased in ABA-treated abr seedlings, suggesting that the abr mutation affects stress response as well as ABA responses. Interestingly, seedlings accumulating anthocyanins exhibited more tolerance to mannitol and NaCl compared to wild type. We propose that ABA-induced H2O2 generation triggers the foliar anthocyanins accumulation, which, in turn, enhances the abiotic stress tolerance in abr mutant.

Differential sensitivity of metabolic pathways in sugar beet roots to combined salt, heat, and light stress.

Plants in nature commonly encounter combined stress scenarios. The response to combined stressors is often unpredictable from the response to single stresses. To address stress interference in roots, we applied salinity, heat, and high light to hydroponically grown sugar beet. Two main patterns of metabolomic acclimation were apparent. High salt of 300 mM NaCl considerably lowered metabolite amounts, for example, those of most amino acids, γ-amino butyric acid (GABA), and glucose. Very few metabolites revealed the opposite trend with increased contents at high salts, mostly organic acids such as citric acid and isocitric acid, but also tryptophan, tyrosine, and the compatible solute proline. High temperature (31°C vs. 21°C) also frequently lowered root metabolite pools. The individual effects of salinity and heat were superimposed under combined stress. Under high light and high salt conditions, there was a significant decline in root chloride, mannitol, ribulose 5-P, cysteine, and l-aspartate contents. The results reveal the complex interaction pattern of environmental parameters and urge researchers to elaborate in much more detail and width on combinatorial stress effects to bridge work under controlled growth conditions to growth in nature, and also to better understand acclimation to the consequences of climate change.